Targeted metabolomics combined with machine learning to identify and validate new biomarkers for early SLE diagnosis and disease activity.

BACKGROUND: The early diagnosis of systemic lupus erythematosus (SLE) and the assessment of disease activity progression remain a great challenge. Targeted metabolomics has great potential to identify new biomarkers of SLE. METHODS: Serum from 44 healthy participants and 89 SLE patients were analyzed using HM400 high-throughput targeted metabolomics. Machine learning (ML) with seven learning models and trained the model several times iteratively selected the two best prediction model in a competitive way, which were independent validated by enzyme-linked immunosorbent (ELISA) with 90 SLE patients. RESULTS: In this study, 146 differential metabolites, most of them organic acids, amino acids, and bile acids, were detected between patients with initial SLE and healthy participants, and 8 potential biomarkers were found by intersection of ML and statistics (area under the curve [AUC] > 0.95) showing a significant positive correlation with clinical indicators. In addition, we identified and validated 2 potential biomarkers for SLE classification (P < 0.05, AUC > 0.775; N-Methyl-L-glutamic acid, L-2-aminobutyric acid) showing a significant correlation with the SLE Disease Activity Index. These differential metabolites were mainly involved in metabolic pathways, amino acid biosynthesis, 2-oxocarboxylic acid metabolism and other pathways. CONCLUSION: This study indicated that the tricarboxylic acid cycle might be associated with SLE drug therapy. We identified 8 diagnostic models biomarkers and 2 biomarkers that could be used to identify initial SLE and distinguish different activity degree, which will promote the development of new tools for the diagnosis and evaluation of SLE.

Pancancer analysis uncovers an immunological role and prognostic value of the m6A reader IGF2BP2 in pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors worldwide with a dismal prognosis and high relapse rate. PDAC is considered a "cold cancer" for which immunotherapy is not effective. Therefore, to improve the prognosis for PDAC patients, it is urgent to explore the mechanism driving its insensitivity to immunotherapy. MATERIALS AND METHODS: We conducted pancancer analyses to test IGF2BP family expression and survival in patients with different cancers via TCGA and GETx databases. Then, we determined the immunological role and prognostic value of IGF2BP2 in vitro, in vivo and in clinical specimens. RESULTS: In the present study, we found that the m6A reader IGF2BP2 was the most clinically relevant member of the IGF2BP family for pancreatic cancer. High expression of IGF2BP2 was most associated with poor prognosis and an immunosuppressive microenvironment in PDAC. By IGF2BP2 knockdown, we found that tumor cell proliferation and invasive ability were significantly diminished. Importantly, we found that IGF2BP2 expression was closely associated with high expression of immunosuppressive molecules such as PD-L1. IGF2BP2 modulated downstream PD-L1 expression by regulating its mRNA stability via m6A methylation control, and we obtained the same verification in animal experiments and human tissue specimens. CONCLUSION: Our study contributes to existing knowledge regarding the IGF2BP2-regulated PD-L1 signaling pathway as a potential prognostic and immune biomarker in pancreatic cancer.

Ameliorative effect of dandelion (Taraxacum officinale) peptides on benzo(a)pyrene-induced oxidative stress and inflammation in human umbilical vein endothelial cells.

Dandelion (Taraxacum officinale) is widely consumed as a health food and a traditional medicine. However, the protective effect of dandelion bio-active peptides (DPs) against polycyclic aromatic hydrocarbon-induced blood vessel inflammation and oxidative damage is not well documented. In the current study, four novel DPs were isolated using an activity tracking method. The protective activity of the DPs against benzo(a)pyrene (Bap)-induced human umbilical vein endothelial cell (HUVEC) damage was explored. The results indicated that DP-2 [cycle-(Thr-His-Ala-Trp)] effectively inhibited Bap-induced reactive oxygen species (ROS) and malondialdehyde (MDA) overproduction and reinforced antioxidant enzyme activity while inhibiting the production of inflammatory factors in HUVECs. Moreover, DP-2 increased NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and nuclear factor E2-releated factor 2 expression levels by activating the PI3K/Akt signaling pathway. In addition, DP-2 attenuated Bap-induced HUVEC apoptosis via the Bcl-2/Bax/cytochrome c apoptotic pathway. These results suggest that DP-2 is a promising compound for protecting HUVECs from Bap-induced inflammatory and oxidative damage.

Ozone protects cardiomyocytes from myocardial ischemia-reperfusion injury through miR-200c/FOXO3 axis.

PURPOSE: Myocardial ischemia-reperfusion injury (I/R) is a detrimental process contributing to the pathological progression of coronary artery diseases. Studies indicate that miRNAs are implicated in ischemic heart disease, and ozone therapy could protect the heart from ischemic heart disease. In this study, we investigated the effect of ozone on miR-200c expression and the potential role of miR-200c in an I/R myocardial injury model. METHODS: A myocardial cellular model of I/R was established to detect the expression of miR-200c. Cardiomyocytes with I/R induction were treated with ozone as a cellular model to detect miR-200 expression and investigate its functional roles. The downstream target of miR-200c was predicted with Starbase online tools and validated by dual luciferase reporter assay. The function of miR-200c/FOXO3 axis in I/R was examined by CCK-8 proliferation and apoptotic assays. RESULTS: miR-200c was upregulated in primary cardiomyocytes of the I/R model. In cardiomyocyte cells, cell proliferation in the I/R group was significantly impaired, which could be partially rescued by miR-200c inhibitor or ozone treatment. Cell death detected by LDH release and apoptosis assay in the I/R model could also be inhibited by miR-200c inhibitor or ozone treatment. FOXO3 was identified as a downstream target of miR-200c, which was induced by ozone treatment and suppressed by miR-200c. Silencing FOXO3 abrogated the protective effect of ozone treatment on the I/R cell model. CONCLUSION: Overall, our results suggest that ozone plays a cardio-protective role in I/R through regulating miR-200/FOXO3 axis, and indicate that targeting miR-200/FOXO3 axis could potentially alleviate I/R.

Effect of early-life exposure to PM2.5 on childhood asthma/wheezing: a birth cohort study.

BACKGROUND: Although studies have investigated the association between early-life exposure to fine particulate matter (PM2.5 ) and childhood asthma/wheezing, results are inconsistent and the susceptible exposure window remains largely unknown. METHODS: A prospective birth cohort study was conducted to recruit pregnant women during their early pregnancy, and to follow up them and their children up to 3-4 years old. Diagnosis of asthma/wheezing was extracted from children's medical records. A spatiotemporal land-use regression (ST-LUR) model was used to assess maternal exposure to PM2.5 during pregnancy and their children's exposure after birth. The Cox proportional hazards model and accelerated failure time model (for violation of proportional hazards assumption) were applied to estimate the effects of prenatal and postnatal exposures to PM2.5 on the risk of childhood asthma/wheezing. RESULTS: A total of 3725 children were included, and 392 children (10.52%) were diagnosed with asthma/wheezing. Both prenatal and postnatal exposures to PM2.5 were positively associated with the risk of asthma/wheezing. Each interquartile range (IQR) increment in PM2.5 exposure during the entire pregnancy (4.8 µg/m3 ) and the period from birth to the end of follow-up (1.5 µg/m3 ) was associated with adjusted hazard ratios (HRs) of 1.44 [95% confidence interval (CI): 1.13, 1.85] and 2.74 (95% CI: 2.59, 2.91), respectively. Subgroup analyses showed greater HRs for PM2.5 exposures during the pseudoglandular stage (6-16 gestational weeks [GWs]: IQR = 4.8 µg/m3 , HR = 1.10, 95% CI: 1.02, 1.18) and canalicular stage (16-24 GWs: IQR = 4.8 µg/m3 , HR = 1.13, 95% CI:1.03, 1.23) than other stages, and also showed significant effects in the first three-year period after birth (IQR = 1.5 µg/m3 , HR = 2.37, 95% CI: =2.24, 2.51). CONCLUSION: Higher prenatal and postnatal PM2.5 exposures may increase the risk of childhood asthma/wheezing. The pseudoglandular stage, canalicular stage, and the first three years after birth may be key susceptible to exposure windows.

Effect of maternal ozone exposure before and during pregnancy on wheezing risk in offspring: A birth cohort study in Guangzhou, China.

Ozone (O3) exposure may lead to the development and exacerbation of asthma or wheezing in postnatal children; however, it has rarely been studied before and during pregnancy. Wheezing is one of the most common symptoms when diagnosing of asthma; thus, we investigated the associations of O3 exposure before and during pregnancy with wheezing in preschool children and the potential susceptible exposure windows from a heavily polluted city in China. This population-based birth cohort study, which included 3725 mother-child pairs from Guangzhou, began in 2016, and the follow-up period ended on July 31, 2020. We used a spatiotemporal land-use-regression model combined with activity patterns to estimate the daily O3 exposure levels during the pre-pregnancy period and each trimester, and wheezing was recorded by reviewing medical records. We used the Cox proportional hazard model to quantify the effects of O3 exposure on childhood wheezing adjusted for potential confounders. No significant association was detected between pre-pregnancy exposure to O3 and childhood wheezing. However, increased ambient O3 exposures throughout pregnancy and in the second trimester were positively associated with the risk of childhood wheezing, with hazard ratios (HRs) and 95% confident intervals (CIs) per interquartile range (IQR) increment of 1.22 (95% CI: 1.04-1.44) and 1.31 (95% CI: 1.09-1.58), respectively. The effects of maternal O3 exposure on childhood wheezing risk was stronger when the exposure occurred in the warm conception season (P < 0.05). Significant childhood wheezing risk could be attributable to maternal O3 exposure, especially during the second trimester and with warm-season conception in Guangzhou. Further cohorts of children, particularly school age children who have more robust asthma diagnoses, should be investigated in the future.

The reliability, validity and screening effect of the happiness index scale among inpatients in a general hospital.

BACKGROUND: The Happiness Index Scale (HIS) is a newly developed scale by our group to screen for common psychological illnesses among general hospital inpatients. This study aimed to analyze the reliability, validity and screening effect of the HIS and to explore its clinical application. METHODS: From April 1, 2021, to December 31, 2021, a total of 8405 continuous inpatients were enrolled from different departments of a large tertiary general hospital with 1385 inpatient beds in Guangzhou, Guangdong Province, China. Using a cross-sectional survey design, each participant was assessed with the Patient Health Questionnaire 9(PHQ-9), Generalized Anxiety Disorder 7 items(GAD-7), Athens Insomnia Scale (AIS), Columbia Suicide Severity Rating Scale (C-SSRS) and HIS within 24 h of admission. McDonald's ω coefficient, the Guttman split-half coefficient and the test-retest reliability coefficient were used to evaluate the reliability of the HIS and the construct validity and criterion validity of the validity tests. Scores on the PHQ-9, GAD-7, AIS, and C-SSRS were used as the gold standard tools to analyze the screening effect of the HIS. RESULTS: The HIS exhibited very good reliability, with a McDonald's ω coefficient of 0.825, a Guttman split-half coefficient of 0.920 and a test-retest reliability coefficient of 0.745 (P < 0.05). Confirmatory factor analysis showed a satisfactory model fitting index with a χ2/df = 2.602, a root mean squared error of approximation (RMSEA) of 0.014, a standardized root mean square residual (SRMR) of 0.010, a comparative fit index (CFI) of 0.992, and a Tucker-Lewis index (TLI) of 0.983. The correlation coefficient between the total score of each dimension of the scale and the corresponding criterion was 0.854 ~ 0.949 (P < 0.001). The HIS showed a very good distinguishing effect. The average HIS score of inpatients who screened positive for psychological problems was significantly higher than that of inpatients who screened negative for psychological problems (t = 3790.619, P < 0.001). The effect size was very large (Cohens d = 2.695, 95% CI = 2.630 ~ 2.761). Approximately 90.2% of the positive and negative screening results of the HIS were matched with the gold standard tools, with a kappa value of 0.747 (P < 0.001). The screening effect test showed a sensitivity (true positive rate) of 92.9% and a specificity (true negative rate) of 89.5%. CONCLUSION: The HIS exhibited satisfactory reliability and validity and a clinically meaningful screening effect with a much shorter version compared to the commonly used screening scales. Thus, it could potentially be useful as the first screening step to rule out psychological conditions for inpatients in general hospitals or to remind medical teams of further psychological concerns.

Associations of COVID-19 lockdown with gestational length and preterm birth in China.

BACKGROUND: The effects of COVID-19 lockdown measures on maternal and fetal health remain unclear. We examined the associations of COVID-19 lockdown with gestational length and preterm birth (PTB) in a Chinese population. METHODS: We obtained medical records of 595,396 singleton live infants born between 2015 and 2020 in 5 cities in Guangdong Province, South China. The exposed group (N = 101,900) included women who experienced the COVID-19 Level I lockdown (1/23-2/24/2020) during pregnancy, while the unexposed group (N = 493,496) included women who were pregnant during the same calendar months in 2015-2019. Cumulative exposure was calculated based on days exposed to different levels of emergency responses with different weighting. Generalized linear regression models were applied to estimate the associations of lockdown exposure with gestational length and risk of PTB (< 37 weeks). RESULTS: The exposed group had a shorter mean gestational length than the unexposed group (38.66 vs 38.74 weeks: adjusted ß = - 0.06 week [95%CI, - 0.07, - 0.05 week]). The exposed group also had a higher risk of PTB (5.7% vs 5.3%; adjusted OR = 1.08 [95%CI, 1.05, 1.11]). These associations seemed to be stronger when exposure occurred before or during the 23rd gestational week (GW) than during or after the 24th GW. Similarly, higher cumulative lockdown exposure was associated with a shorter gestational length and a higher risk of PTB. CONCLUSIONS: The COVID-19 lockdown measures were associated with a slightly shorter gestational length and a moderately higher risk of PTB. Early and middle pregnancy periods may be a more susceptible exposure window.

Hypothesis paper: electroacupuncture targeting the gut-brain axis to modulate neurocognitive determinants of eating behavior-toward a proof of concept in the obese minipig model.

Acupuncture has thousands of years of history and perspective for the treatment of many health problems and disorders. Beneficial effects of acupuncture on obesity have been demonstrated at various levels in animals and clinical trials, with almost no adverse effect, even when combined with local electrical stimulation, i.e., electroacupuncture (EA), a way to potentiate the effects of acupuncture. However, there is still scattered evidence about the impact of EA on brain functions related to the control of eating behavior, and notably on the gut-brain axis mechanisms involved in these putative central modulations. During the past 10 years, we have described a convincing diet-induced obese minipig model, and successfully implemented brain imaging and neurocognitive approaches to challenge mechanistic hypotheses and innovative therapeutic strategies. In the present article, we propose to confront the current literature on the acupuncture and EA effects on the gut-brain axis and obesity with the latest developments in nutrition and neuroscience research using the minipig model. Our aims are to (a) elaborate functional hypotheses on the gut-brain mechanisms underlying EA effects on obesity, and especially on the role of the vagus nerve, and (b) present the rational for testing these hypotheses in the minipig model.

Feasibility of a pilot program for COVID-19 convalescent plasma collection in Wuhan, China.

BACKGROUND: A novel coronavirus has caused an international outbreak. Currently, there are no specific therapeutic agents for coronavirus infections. Convalescent plasma (CP) therapy is a potentially effective treatment option. METHODS: Patients who had recovered from COVID-19 and had been discharged from the hospital for more than 2 weeks were recruited. COVID-19 convalescent plasma (CCP)-specific donor screening and selection were performed based on the following criteria: 1) aged 18-55 years; 2) eligible for blood donation; 3) diagnosed with COVID-19; 4) had two consecutive negative COVID-19 nasopharyngeal swab tests based on PCR (at least 24 hr apart) prior to hospital discharge; 5) had been discharged from the hospital for more than 2 weeks; and 6) had no COVID-19 symptoms prior to convalescent plasma donation. In addition, preference was given to CCP donors who had a fever lasting more than 3 days or a body temperature exceeding 38.5°C (101.3°F), and who donated 4 weeks after the onset of symptoms. CCP collection was performed using routine plasma collection procedures via plasmapheresis. In addition to routine donor testing, the CCP donors' plasma was also tested for SARS-CoV-2 nucleic acid and S-RBD-specific IgG antibody. RESULTS: Of the 81 potential CCP donors, 64 (79%) plasma products were collected. There were 18 female donors and 46 male donors. There were 34 first-time blood donors and 30 repeat donors. The average time between CCP collection and initial symptom onset was 49.1 days, and the average time between CCP collection and hospital discharge was 38.7 days. The average volume of CCP collected was 327.7 mL. All Alanine transaminase (ALT) testing results met blood donation requirements. HIV Ag/Ab, anti-HCV, anti-syphilis, and HBsAg were all negative; NAT for HIV, HBV, and HCV were also negative. In addition, all of the CCP donors' plasma units were negative for SARS-CoV-2 RNA. Of the total 64 CCP donors tested, only one had an S-RBD-specific IgG titer of 1:160, all others had a titer of ≥1:320. CONCLUSION: Based on a feasibility study of a pilot CCP program in Wuhan, China, we demonstrated the success and feasibility of CCP collection. In addition, all of the CCP units collected had a titer of ≥1:160 for S-RBD-specific IgG antibody, which met the CCP quality control requirements based on the Chinese national guidelines for CCP.

Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation.

BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION: This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.

Visual, sensitive and rapid event-specific detection of genetically modified potato EH92-527-1 by loop-mediated isothermal amplification method.

To date, studies on the application of loop-mediated isothermal amplification (LAMP) in the detection of genetically modified organisms (GMOs) are stably increasing and demonstrates LAMP is a potential and promising method for on spot identification of GMOs. However, little information is known for detection of GM potato events by LAMP. In this report, we developed an optimized and visual LAMP assay with high specificity and sensitivity to rapidly amplify genomic DNA of potato EH92-527-1 within 45 min. The limit of detection of LAMP in our study is 10-fold higher than the conventional PCR. Furthermore, LAMP products can be directly observed via naked eyes by addition of SYBR Green I without gel electrophoresis analysis and PCR-based equipment. Therefore, the LAMP assay developed in this paper provides an efficient, convenient and cost-effective tool for the detection of GM potato EH92-527-1.

Positive-contrast susceptibility imaging based on first-order primal-dual optimization.

PURPOSE: To achieve faster reconstruction and better imaging quality of positive-contrast MRI based on the susceptibility mapping by incorporating a primal-dual (PD) formulation. METHODS: The susceptibility-based positive contrast MR technique was applied to estimate arbitrary magnetic susceptibility distributions of the metallic devices using a kernel deconvolution algorithm with a regularized ℓ1 minimization. The regularized positive-contrast inversion problem and its PD formulation were derived. The visualization of the positive contrast and convergence behavior of the PD algorithm were compared with those of the nonlinear conjugate gradient algorithm, fast iterative soft-thresholding algorithm, and alternating direction method of multipliers. These methods were tested and validated on computer simulations and phantom experiments. RESULTS: The PD approach could provide a faster reconstruction time compared with other methods. Experimental results showed that the PD algorithm could achieve comparable or even better visualization and accuracy of the metallic interventional devices in positive-contrast imaging with different SNRs and orientations to the B0 field. CONCLUSION: A susceptibility-based positive-contrast imaging technique by PD algorithm was proposed. The PD approach has more superior performance than other algorithms in terms of reconstruction time and accuracy for imaging the metallic interventional devices.

CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans.

PURPOSE: Vascular disrupting therapy of cancer has become a promising approach not only to regress tumor growth directly but also to boost the delivery of chemotherapeutics in the tumor. An imaging approach to monitor the changes in tumor vascular permeability, therefore, has important applications for monitoring of vascular disrupting therapies. METHODS: Mice bearing CT26 subcutaneous colon tumors were injected intravenously with 150 kD dextran (Dex150, diameter, d~ 20 nm, 375 mg/kg), tumor necrosis factor-alpha (TNF-α; 1 µg per mouse), or both (n = 3 in each group). The Z-spectra were acquired before and 2 h after the injection, and the chemical exchange saturation transfer (CEST) signals in the tumors as quantified by asymmetric magnetization transfer ratio (MTRasym ) at 1 ppm were compared. RESULTS: The results showed a significantly stronger CEST contrast enhancement at 1 ppm (∆MTRasym = 0.042 ± 0.002) in the TNF-α-treated tumors than those by Dex150 alone (∆MTRasym = 0.000 ± 0.005, P = 0.0229) or TNF-α alone (∆MTRasym = 0.002 ± 0.004, P = 0.0264), indicating that the TNF-α treatment strongly augmented the tumor uptake of 150 kD dextran. The MRI findings were verified by fluorescence imaging and immunofluorescence microscopy. CONCLUSIONS: High molecular weight dextrans can be used as safe and sensitive CEST MRI contrast agents for monitoring tumor response to vascular disrupting therapy and, potentially, for developing dextran-based theranostic drug delivery systems.

Characterization of tumor vascular permeability using natural dextrans and CEST MRI.

PURPOSE: To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability. METHODS: Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N = 5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6 nm) and 70 kD (D70, 12 nm) dextran at a dose of 375 mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40 min after each injection using a dynamic CEST imaging scheme. RESULTS: All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9 ppm. The detectability and effects of pH and saturation conditions (B1 and Tsat ) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant "dexCEST" enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry. CONCLUSIONS: As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems. Magn Reson Med 79:1001-1009, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The effects of apheresis, storage time, and leukofiltration on microparticle formation in apheresis platelet products.

BACKGROUND: Although platelet microparticles (PMPs) were the most abundant micoparticles (MPs) in platelet (PLT) products, other MPs and their parental cells can also be brought into the plasma during PLT apheresis. However, the effects of PLT apheresis, storage time, and leukofiltration on these MPs remain largely unclear. STUDY DESIGN AND METHODS: Apheresis PLTs with or without leukofiltration were stored in 22 ± 2 °C for 5 days. PLT-poor plasma (PPP) was generated by centrifugation of donor blood or PLT products at 2500 × g for 15 minutes on the point day. PPP was labeled with CD41a (PLT-derived MP, PMP), CD235 (red blood cell-derived MP, RMP), CD45 (leukocyte-derived MP, LMP), CD14 (monocyte-derived MP, MMP), and CD144 (endothelial cell-derived MP, EMP), and then measured by flow cytometry. RESULTS: Higher-level TMPs (total microparticles) and PMPs, but lower-level RMPs, LMPs, and MMPs were detected in fresh PLTs on the day of collection compared with those before collection. During storage, TMP, PMP, and RMP counts were significantly higher on Day 3 and Day 5, but MMP and LMP counts were only marginally higher on Day 3 in PLT supernatants. There were no significant differences in MP levels in PLTs with or without leukofiltration. CONCLUSION: MP formation was affected by the apheresis procedure. RMPs, LMPs and MMPs were lower after PLT apheresis. During storage, TMPs, PMPs, RMPs, LMPs, and MMPs were found to be higher in PLT supernatants. Leukofiltration exerted no significant effect on all MPs in PLT products.

Cardiovascular magnetic resonance black-blood thrombus imaging for the diagnosis of acute deep vein thrombosis at 1.5 Tesla.

BACKGROUND: The aim was to investigate the feasibility of a cardiovascular magnetic resonance (CMR) black-blood thrombus imaging (BBTI) technique, based on delay alternating with nutation for tailored excitation black-blood preparation and a variable flip angle turbo-spin-echo readout, for the diagnosis of acute deep vein thrombosis (DVT) at 1.5 T. METHODS: BBTI was conducted in 15 healthy subjects and 30 acute DVT patients. Contrast-enhanced CMR venography (CE-CMRV) was conducted for comparison and only performed in the patients. Apparent contrast-to-noise ratios between the thrombus and the muscle/lumen were calculated to determine whether BBTI could provide an adequate thrombus signal for diagnosis. Two blinded readers assessed the randomized BBTI images from all participants and made independent decisions on the presence or absence of thrombus at the segment level. Images obtained by CE-CMRV were also randomized and assessed by the two readers. Using the consensus CE-CMRV as a reference, the sensitivity, specificity, positive and negative predictive values, and accuracy of BBTI, as well as its diagnostic agreement with CE-CMRV, were calculated. Additionally, diagnostic confidence and interobserver diagnostic agreement were evaluated. RESULTS: The thrombi in the acute phase exhibited iso- or hyperintense signals on the BBTI images. All the healthy subjects were correctly identified from the participants based on the segment level. The diagnostic confidence of BBTI was comparable to that of CE-CMRV (3.69 ± 0.52 vs. 3.70 ± 0.47). High overall sensitivity (95.2%), SP (98.6%), positive predictive value (96.0%), negative predictive value (98.3%), and accuracy (97.7%), as well as excellent diagnostic and interobserver agreements, were achieved using BBTI. CONCLUSION: BBTI is a reliable, contrast-free technique for the diagnosis of acute DVT at 1.5 T.

Ultrahigh b-values MRI in normal human prostate: Initial research on reproducibility and age-related differences.

PURPOSE: To investigate the reproducibility of diffusion-weighted imaging (DWI) with ultrahigh b-values, and analyze the age-related differences in normal prostates. MATERIALS AND METHODS: In all, 67 healthy participants were divided into three age groups (group A, 15-30 years; group B, 31-50 years; group C, ≥51 years), and underwent DWI scanning twice with 15 b-factors from 0 to 3000 at 3.0T. Triexponential fits were applied to calculate the molecular diffusion coefficient (D), the pseudo-diffusion coefficient (D*), the ultrahigh apparent diffusion coefficient (ADCuh ), and perfusion fraction (f). The interobserver and short-term interscan reproducibility were evaluated, and the change in these parameters with age were assessed. RESULTS: The D, ADCuh , and f values presented good to excellent reproducibility. With increasing age, a trend of increasing D values was observed, with significant difference in both peripheral zone (PZ, P = 0.01) and central gland (CG, P = 0.01) of normal prostate tissue. The f value increased in the CG beginning at 50 years of age while the ADCuh value decreased in the PZ after 50 years of age; all of them showed significant differences between groups A and C and groups B and C (P = 0.01/0.01). CONCLUSION: The D, ADCuh , and f values have good to excellent reproducibility in the normal prostate, and these values change with age. The ultrahigh b-values magnetic resonance imaging (MRI) can provide additional information (ADCuh ), which is different from the IVIM (intravoxel incoherent motion)-derived parameters. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:801-812.

Black-blood thrombus imaging (BTI): a contrast-free cardiovascular magnetic resonance approach for the diagnosis of non-acute deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a common but elusive illness that can result in long-term disability or death. Accurate detection of thrombosis and assessment of its size and distribution are critical for treatment decision-making. In the present study, we sought to develop and evaluate a cardiovascular magnetic resonance (CMR) black-blood thrombus imaging (BTI) technique, based on delay alternating with nutation for tailored excitation black-blood preparation and variable flip angle turbo-spin-echo readout, for the diagnosis of non-acute DVT. METHODS: This prospective study was approved by institutional review board and informed consent obtained from all subjects. BTI was first conducted in 11 healthy subjects for parameter optimization and then conducted in 18 non-acute DVT patients to evaluate its diagnostic performance. Two clinically used CMR techniques, contrast-enhanced CMR venography (CE-MRV) and three dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE), were also conducted in all patients for comparison. All images obtained from patients were analyzed on a per-segment basis. Using the consensus diagnosis of CE-MRV as the reference, the sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV), and accuracy (ACC) of BTI and MPRAGE as well as their diagnostic agreement with CE-MRV were calculated. Besides, diagnostic confidence and interreader diagnostic agreement were evaluated for all three techniques. RESULTS: BTI with optimized parameters effectively nulled the venous blood flow signal and allowed directly visualizing the thrombus within the black-blood lumen. Higher SE (90.4% vs 67.6%), SP (99.0% vs. 97.4%), PPV (95.4% vs. 85.6%), NPV (97.8% vs 92.9%) and ACC (97.4% vs. 91.8%) were obtained by BTI in comparison with MPRAGE. Good diagnostic confidence and excellent diagnostic and interreader agreements were achieved by BTI, which were superior to MPRAGE on detecting the chronic thrombus. CONCLUSION: BTI allows direct visualization of non-acute DVT within the dark venous lumen and has the potential to be a reliable diagnostic tool without the use of contrast medium.