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Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.
Subject(s)
Atrophy , Cognition , Cognitive Dysfunction , Gray Matter , Magnetic Resonance Imaging , Multiple Sclerosis , Humans , Gray Matter/pathology , Gray Matter/diagnostic imaging , Cross-Sectional Studies , Multiple Sclerosis/complications , Multiple Sclerosis/psychology , Cognitive Dysfunction/etiology , Cerebral Cortex/pathology , Cerebral Cortex/diagnostic imaging , Neuropsychological Tests , Male , FemaleABSTRACT
Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Subject(s)
Ductus Arteriosus, Patent , Infant, Premature, Diseases , Persistent Fetal Circulation Syndrome , Infant , Infant, Newborn , Male , Humans , Female , Ductus Arteriosus, Patent/drug therapy , Infant, Premature , Cross-Sectional Studies , Ibuprofen/therapeutic use , Infant, Very Low Birth Weight , Infant, Premature, Diseases/therapyABSTRACT
Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ2 test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m2) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.
Subject(s)
Diabetes, Gestational , Hypertension, Pregnancy-Induced , Pre-Eclampsia , Premature Birth , Sleep Apnea, Obstructive , Infant, Newborn , Pregnancy , Infant , Humans , Female , Pre-Eclampsia/epidemiology , Hypertension, Pregnancy-Induced/epidemiology , Retrospective Studies , Sleep Apnea, Obstructive/epidemiology , Diabetes, Gestational/epidemiologyABSTRACT
Acute pancreatitis is one of the common surgical acute abdominal diseases. Since people first recognized acute pancreatitis in the middle of the nineteenth century, a diversified minimally invasive treatment model with standardization has been formed today. According to the main line of surgical intervention of acute pancreatitis treatment,this period can be roughly divided into five stages:exploration stage, conservative treatment stage, pancreatectomy stage, debridement and drainage of the pancreatic necrotic tissue stage, and minimally invasive treatment as the first choice led by the multidisciplinary team mode stage. Throughout history, the evolution and progress of surgical intervention strategies for acute pancreatitis cannot be separated from the progress of science and technology, the update of treatment concepts and the further understanding of the pathogenesis. This article will summarize the surgical characteristics of acute pancreatitis treatment at each stage to explain the development of surgical treatment of acute pancreatitis,to help investigate the development of surgical treatment of acute pancreatitis in the future.
Subject(s)
Pancreatitis, Acute Necrotizing , Humans , Acute Disease , Debridement , Drainage , Pancreatitis, Acute Necrotizing/surgery , Pancreatitis, Acute Necrotizing/pathology , Treatment OutcomeABSTRACT
Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Subject(s)
Bronchopulmonary Dysplasia , Retinopathy of Prematurity , Sepsis , Infant , Infant, Newborn , Humans , Birth Weight , Intensive Care Units, Neonatal , Retrospective Studies , Tertiary Care Centers , Infant, Extremely Low Birth Weight , Gestational Age , Infant, Extremely Premature , Sepsis/epidemiology , Retinopathy of Prematurity/epidemiology , Bronchopulmonary Dysplasia/epidemiologyABSTRACT
The Energy iNNovation's XuanLong-50 is a spherical torus experiment with up to 10 s plasma operation duration. A 3 J/50 Hz pulsed laser is used in the Thomson scattering diagnostic system that is developed to measure the time evolutions of plasma electron temperature and density profiles. The expected laser pulse number is about 7.5 × 106/year with a power load of 150 W. To meet at least 1-year lifetime requirement, a Chevron type beam dump with polished molybdenum plates is designed and fabricated, which absorbs the laser beam energy in a 3D structure to reduce the laser fluence deposited on the material surface. To prevent the backscattered stray light from interfering with the Thomson scattering measurements, a 7.5 m beam path with folding mirrors is set between the beam dump and the plasma scattering volumes. Details of the beam dump design procedure including the laser beam profile control, multi-pulse laser damage threshold, heat dissipation, Zemax modeling, folding mirror selection, and beam path enclosure are presented together with the testing results.
ABSTRACT
Polychromators are most frequently used in Thomson scattering (TS) diagnostics to analyze the scattered light spectrum and intensity so that the plasma electron temperature (Te) and density (ne) can be derived. For Te measurements, the spectral response of the polychromator channels and the relative spectral responsivities need to be calibrated. The spectral response is calibrated with a bromine tungsten lamp and a monochromator in a conventional way. A novel method for calibrating the relative spectral responsivities of the polychromators is described in detail. A broadband pulsed Light Emission Diode (LED) is used, which has a spectral irradiance similar to that of the TS spectrum, and the LED can be driven in pulse mode with the pulse width similar to the TS signal pulse width of about 10-20 ns full width at half maximum. This new method allows for the calibration to be done after the polychromator is fully installed, and in situ system calibration can be easily performed, showing the advantages of accuracy, simplicity, efficiency, and flexibility. For ne measurements, absolute sensitivity calibration is done by Rayleigh scattering with argon gas. Formulas for calculating the plasma density from the calibration data and the polychromator signals from the off-laser wavelength channels are presented.
ABSTRACT
A 15-point Thomson scattering diagnostic system is developed for ENN's spherical torus experiment XuanLong-50 (EXL-50). A BeamTech laser with 3 J/pulse (1064 nm wavelength) at 50 Hz repetition rate is chosen for measurements during EXL-50 plasma operations. To enable measurements at low density (â¼0.5 × 1018 m-3) plasma operations, the opto-mechanical subsystems are carefully designed to maximize the collection and transmission of the scattered light and to minimize the stray light level. In addition, the high bandwidth trans-impedance amplifiers and segmented high speed waveform digitizers allow for the application of muti-pulse averaging to further improve the signal-to-noise ratio. Details of the diagnostic system are described and initial experimental results are presented.
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Eighty-four amateur half marathon athletes (168 side feet) in Beijing from October 2018 to May 2021 were recruited, and their age, gender and whether they have foot pain were collected, including 44 males and 40 females, aged from 21 to 60 (40.7±9.3) years. All participants underwent bipedal magnetic resonance imaging (MRI) examinations, and the degree of foot pain was graded by foot ankle injury scale (FASS scale). The relationship between MRI features and the foot pain of amateur half marathon athletes were analyzed. The study found that the proportion of foot pain symptoms among amateur half marathon athletes in Beijing was high(122/168), and the MRI manifestations were mainly heel tendinitis and plantar fasciitis, which accounted for about 59.5% of all cases.
Subject(s)
Foot Injuries , Marathon Running , Adult , Athletes , Female , Foot , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Long-range connections are more severely damaged and relevant for cognition in long-standing MS. However, the evolution of such coordinated network damage in patients with MS is unclear. We investigated whether short- and long-range structural connections sustained equal damage in early-stage MS. MATERIALS AND METHODS: Sixteen patients with early-stage MS and 17 healthy controls were scanned by high-resolution, multishell diffusion imaging on 7T MR imaging and assessed cognitively. We investigated macrostructural properties in short- and long-range fibers and of microstructural metrics derived from 2 quantitative diffusion MR imaging models: DTI and neurite orientation dispersion and density imaging. RESULTS: Patients had significant WM integrity damage-that is, higher radial diffusivity and a lower intracellular volume fraction in the focal WM lesions. Compared with the healthy controls, the patients had noticeable microstructure changes in both short- and long-range fibers, including increased radial diffusivity, mean diffusivity, and axial diffusivity. Z scores further indicated greater damage in the short-range fibers than in the long-range fibers. CONCLUSIONS: Our findings demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging.
Subject(s)
White Matter , Brain/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Humans , Magnetic Resonance Imaging/methods , Neurites , White Matter/pathologyABSTRACT
OBJECTIVE: To compare 3 commercial immunogenic cell death (ICD) inducers, namely Chlorin e6 (Ce6), Neutral Red (NR), and Rose Bengal Sodium salt (RB), for their photosensitive properties, efficacy for photodynamic therapy (PDT) and ICD induction efficiency in antitumor immunotherapy. METHODS: Reactive oxygen species (ROS) probes were used to evaluate the photosensitivity of the 3 ICD inducers, and their capacity for inducing intracellular ROS production was evaluated using a DCFH-DA probe. The cytotoxicity and biocompatibility of the 3 photosensitizers were compared using a CCK-8 kit, and their ICD-inducing efficiency was assessed by detecting the levels of surface-exposed calreticulin (ecto-CRT), high mobility group protein 1 (HMGB1) and adenosine triphosphate (ATP). In the animal experiment, BALB/c mouse models bearing 4T1 cellderived subcutaneous tumor were given intratumoral injection of Ce6 or NR solution (30 µL, 5 mg/mL), followed 2 h later by white light irradiation for 10 min (400 mW/cm2). Body weight and tumor size changes of the mice were monitored, and the percentage of CD8+ T cells in the tumor and IFN-γ+ CD8+ T cells in the spleen were analyzed by flow cytometry 14 days after the treatment. HE and TUNEL staining was used to analyze tumor cell apoptosis in the mice. RESULTS: Among the 3 photosensitizers, Ce6 exhibited the strongest ROS-inducing capability and killing effect on the tumor cells. The results of ectoCRT, HMGB1 and ATP level detection all demonstrated a stronger ICD induction ability of Ce6. In the tumor-bearing mice, the tumor growth in Ce6 and NR groups was significantly inhibited after the treatment. The percentages of CD8+ T cells and IFN-γ+ CD8+ T cells were 12.7% and 7.1% in Ce6 group, respectively, significantly higher than those in NR group (6.1% and 2.8%, respectively; P < 0.05). HE and TUNEL staining revealed obvious tumor cell apoptosis in the tumor tissues in both Ce6 and NR groups, but the therapeutic effect was more prominent in Ce6 group. CONCLUSION: Among the 3 photosensitizers, Ce6 has the highest efficiency for inducing ROS production with the strongest PDT efficacy and ICD induction capability. Ce6 can also increase the number and function of CD8+ T cells in anti-tumor immunotherapy to initiate robust adaptive immune response.
Subject(s)
Antineoplastic Agents , HMGB1 Protein , Neoplasms , Photochemotherapy , Porphyrins , Mice , Animals , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Immunogenic Cell Death , Reactive Oxygen Species/metabolism , CD8-Positive T-Lymphocytes , Photochemotherapy/methods , Immunotherapy , Porphyrins/pharmacology , Cell Line, TumorABSTRACT
A plasma radiation measurement system for a wide spectral range, based on compact Absolute eXtreme UltraViolet (AXUV) silicon photodiodes, has been implemented on the newly constructed ENN XuanLong-50 (EXL-50) spherical tokamak. The system consists of two 16-channel AXUV16ELG arrays and one AXUV63HS1 single-cell detector mounted on ceramic sockets. The two arrays, facing toward the EXL-50 slim central post from two locations inside a top and a side ConFlat 400 port, have 32 view chords covering the interested plasma region in a poloidal cross section at toroidal 330°. The single-cell detector, seated on a retractable feedthrough, could be arranged flexibly with the help of an ultra-high vacuum compatible gate valve. The design details together with considerations on the EXL-50 specific engineering realities and physics requirements are described. Preliminary results from the EXL-50 2020 experimental campaign are presented.
ABSTRACT
To evaluate the efficacy and safety of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) over 75 years. A total of 82 patients with AF who underwent LAAO successfully in Beijing Anzhen Hospital from March 2014 to March 2019 were divided into two groups according to age: the elderly group (aged>75 years) and the young group (aged ≤75 years). Risk of perioperative complications and incidence of ischemic stroke and major bleeding during follow-up were retrospectively analyzed. The results showed that there were no significant differences in procedure-related ischemic stroke(0 vs.1.6%,P=0.768) and major bleeding (0 vs.1.6%,P=0.768) during perioperative period between the two groups. No complications as death or pericardial tamponade occurred in the two group. During a (25.9±15.9) months period of followed up, ischemic stroke event rate was 3.6/100 person-years in the elderly group and 4.9/100 person-years in the young group, respectively. Major bleeding event rate was 2.5/100 person-years in the elderly group and 0/100 person-years in the young group, respectively. Compared with the expected ones, the relative risk reduction (RRR) of stroke in the elderly group was more profound than that in the young group (32.0% vs. 25.0%), while the risk of major bleeding in the young group was significantly lower than that in the elderly group (RRR 100% vs. 56.9%). Therefore, LAAO might be suitable for stroke prevention in the elderly AF patients.
Subject(s)
Atrial Appendage , Atrial Fibrillation , Stroke , Aged , Atrial Appendage/surgery , Atrial Fibrillation/complications , Hemorrhage , Humans , Retrospective Studies , Stroke/etiology , Stroke/prevention & control , Treatment OutcomeABSTRACT
A toroidal soft x-ray array system for spectrum and intensity measurements on the EXL-50 spherical tokamak is described. Silicon drift detectors and digital multichannel analyzers are adopted for all 21 channels of the array, and an average energy resolution of 147 eV at 5.89 keV has been achieved at count rates over 500 kcps. In total, 20 channels of the array are symmetrically observed in both co- and counter-current directions on the EXL-50 mid-plane with a spatial resolution of around 10 cm, and the remaining one serves as a background reference channel. Tungsten emissions from tungsten coating of the limiters on the central post are observed. The influence of hard x rays on measured soft x-ray spectra and system operation is discussed.
ABSTRACT
A tangential hard x-ray (HXR) diagnostic on the newly constructed ENN XuanLong-50 (EXL-50) spherical tokamak for fast electron emission studies is presented. The HXR detection system consists of a symmetrical CdZnTe semiconductor detector array with a spectral sensitivity range of 20-300 keV. 25 channels have been designed on the 270° horizontal vacuum port with 12 sight lines to observe the forward emission, 12 sight lines to observe the backward emission of fast electrons, and 1 for viewing the central. Currently, ten channels have been in operation in the EXL-50 experiments. The systems are designed to measure the x-ray spectra for the estimation of fast electron temperature and electron velocity distribution in the EXL-50 experiment, which will be useful for understanding the dynamics of fast electrons generated by electron cyclotron resonance heating, for plasma instability and transport studies and for the analysis of plasma heating efficiency.
ABSTRACT
ABSTRACT: Objective To study the changes of metabolites in serum and tissues ï¼kidney, liver and heartï¼ of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry ï¼UPLC-Orbitrap HRMSï¼. Multivariate statistical principal component analysis ï¼PCAï¼ and orthogonal partial least square-discriminant analysis ï¼OPLS-DAï¼ were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.
Subject(s)
Metabolomics , Tetracaine , Animals , Biomarkers/metabolism , Chromatography, High Pressure Liquid , Mass Spectrometry , Metabolome , Mice , Mice, Inbred ICRABSTRACT
Objective: To investigate the impact of iron deficiency (ID) on prognosis in heart failure patients with preserved ejection fraction (HFpEF). Methods: A total of 215 consecutive patients with HFpEF, who visited the cardiovascular outpatient department of Beijing Anzhen Hospital, were enrolled in this prospective study. The plasma ferritin level and transferin saturation were measured. Patients were divided into two groups: ID group and non-ID group. ID patients were further divided into absolute ID subgroup and functional ID subgroup. Patients were followed up to 1 year. The endpoints of the study were all-cause mortality and rehospitalization for heart failure (HF). The independent predictors of outcome were determined by Cox regression model. The quality of life of patients was evaluated at the end of the follow-up. Results: The age of this patient cohort was (67±8) years, 39.1% patients were male. The prevalence of ID was 54.4%. Within one year of follow-up, 37 patients (17.2%) died and 70 patients (32.6%) were rehospitalized for HF. Compared to non-ID group, patients in ID group were older, had higher heart rate, lower plasma hemoglobin level and estimated glomerular filtration rate (eGFR) value, had a higher prevalence of anemia and chronic kidney disease (P all<0.05). Kaplan-Meier curves showed that all-cause mortality and rehospitalization for HF in HFpEF patients with ID were higher than patients without ID, and prognosis was similar between patients with absolute ID and functional ID. Multivariable regression analysis showed that ID was an independent predictor for all-cause mortality and rehospitalization for HF in HFpEF patients. The of 6 minutes walking distance was shorter ((356.0±98.3)m vs. (389.2±94.3)m, P=0.023), and the value in Kansas city cardiomyopathy questionnaire was lower ((58.06±10.43) m vs. (61.51±11.64) m, P = 0.039) in patients with ID than patients without ID. Conclusion: In patients with chronic HFpEF, ID is an independent predictor for all-cause mortality and rehospitalization for HF at one year of follow-up, independent of the types of ID.