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1.
Light Sci Appl ; 13(1): 136, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849359

ABSTRACT

Efficient charge-carrier injection and transport in organic light-emitting devices (OLEDs) are essential to simultaneously achieving their high efficiency and long-term stability. However, the charge-transporting layers (CTLs) deposited by various vapor or solution processes are usually in amorphous forms, and their low charge-carrier mobilities, defect-induced high trap densities and inhomogeneous thickness with rough surface morphologies have been obstacles towards high-performance devices. Here, organic single-crystalline (SC) films were employed as the hole-transporting layers (HTLs) instead of the conventional amorphous films to fabricate highly efficient and stable OLEDs. The high-mobility and ultrasmooth morphology of the SC-HTLs facilitate superior interfacial characteristics of both HTL/electrode and HTL/emissive layer interfaces, resulting in a high Haacke's figure of merit (FoM) of the ultrathin top electrode and low series-resistance joule-heat loss ratio of the SC-OLEDs. Moreover, the thick and compact SC-HTL can function as a barrier layer against moisture and oxygen permeation. As a result, the SC-OLEDs show much improved efficiency and stability compared to the OLEDs based on amorphous or polycrystalline HTLs, suggesting a new strategy to developing advanced OLEDs with high efficiency and high stability.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124493, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-38796891

ABSTRACT

6-mercaptopurine (6-MP) is widely used in the treatment of many diseases, but exhibits some serious side effects due to its toxicity. Therefore, it is important and imperative to effectively control and monitoring concentration of 6-MP. Herein, we designed a smartphone-assisted colorimetric sensing platform for 6-MP detection, based on an excellent ß-cyclodextrin modified MnO2 nanosheets (ß-CD@MnO2 NNS) mediated oxidase-like activity. ß-CD@MnO2 NNS can directly oxidizes 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB with color changes, yielding more than 3-fold higher oxidase-like catalytic activity compared with individual MnO2 NNS. After adding 6-MP, ß-CD@MnO2 NNS can be reduced to Mn2+ and lose their oxidase-like properties, resulting in a color and absorbance change for sensitive and selectivity detection of 6-MP. Meanwhile, the smartphone-based color recognition application can intuitively and simply measure the concentration of 6-MP. The limits of detection UV-vis instrument and smartphone were 0.35 µM and 0.86 µM, respectively. This method has also been successfully applied to the detection of real samples. Finally, this study provides a new promising platform for detection of 6-MP and is expected to be used in application of pharmaceutical analysis and biomedicine.


Subject(s)
Colorimetry , Manganese Compounds , Mercaptopurine , Nanostructures , Oxides , Smartphone , beta-Cyclodextrins , Colorimetry/methods , Manganese Compounds/chemistry , beta-Cyclodextrins/chemistry , Oxides/chemistry , Mercaptopurine/analysis , Nanostructures/chemistry , Oxidoreductases/metabolism , Oxidoreductases/chemistry , Limit of Detection , Humans , Benzidines/chemistry
3.
Front Mol Neurosci ; 16: 1116949, 2023.
Article in English | MEDLINE | ID: mdl-36873107

ABSTRACT

Objectives: Galloway-Mowat syndrome-4 (GAMOS4) is a very rare renal-neurological disease caused by TP53RK gene mutations. GAMOS4 is characterized by early-onset nephrotic syndrome, microcephaly, and brain anomalies. To date, only nine GAMOS4 cases with detailed clinical data (caused by eight deleterious variants in TP53RK) have been reported. This study aimed to examine the clinical and genetic characteristics of three unrelated GAMOS4 patients with TP53RK gene compound heterozygous mutations. Methods: Whole-exome sequencing (WES) was used to identify four novel TP53RK variants in three unrelated Chinese children. Clinical characteristics such as biochemical parameters and image findings of patients were also evaluated. Furthermore, four studies of GAMOS4 patients with TP53RK variants were reviewed. In addition, clinical and genetic features were described after a retrospective analysis of clinical symptoms, laboratory data, and genetic test results. Results: The three patients showed facial abnormalities, developmental delays, microcephaly, and aberrant cerebral imaging. Furthermore, patient 1 had slight proteinuria, while patient 2 had epilepsy. However, none of the individuals had nephrotic syndrome, and all were alive for more than 3 years of age. This is the first study to assess four variants in the TP53RK gene (NM_033550.4: c.15_16dup/p.A6Efs*29, c.745A > G/p.R249G, c.185G > A/p.R62H, and c.335A > G/p.Y112C). Conclusion: The clinical characteristics of the three children with TP53RK mutations are significantly different from the known GAMOS4 traits, including early nephrotic syndrome and mortality mainly occurring in the first year of life. This study provides insights into the pathogenic TP53RK gene mutation spectrum and clinical phenotypes of GAMOS4.

4.
Bioorg Chem ; 135: 106481, 2023 06.
Article in English | MEDLINE | ID: mdl-36966672

ABSTRACT

Three series of phenylurea indole derivatives were synthesized with potent inhibitory activities on ABCG2 with simple and efficient synthetic routes. Among these compounds, four phenylurea indole derivatives 3c-3f with extended π system were discovered as the most potent ABCG2 inhibitors, while these compounds showed no inhibition on ABCB1. Compounds 3c and 3f were selected for further investigation to explore the mechanisms of action on reversing ABCG2-mediated multidrug resistance (MDR). The results revealed that compounds 3c and 3f increased the accumulation of mitoxantrone (MX) in ABCG2-overexpressing cells, but they did not alter the expression level or localization of ABCG2 in cells. In addition, both 3c and 3f significantly stimulated the ATP hydrolysis of ABCG2 transporter indicating that they can be competitive substrates of ABCG2 transporter, and thereby increase the accumulation of mitoxantrone in ABCG2-overexpressing H460/MX20 cells. Both 3c and 3f was docked into the drug-binding site of the human ABCG2 transporter protein (PDB 6FFC) with high affinities. This study showed that extending the π system of phenylurea indole derivatives enhanced their inhibitory activities on ABCG2, which may provide a clue for the further research to discover more potent ABCG2 inhibitors.


Subject(s)
Antineoplastic Agents , Humans , Antineoplastic Agents/chemistry , Mitoxantrone/pharmacology , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Drug Resistance, Neoplasm , Phenylurea Compounds/pharmacology , Cell Line, Tumor , Indoles/pharmacology , Neoplasm Proteins/metabolism
5.
Bioorg Chem ; 134: 106438, 2023 05.
Article in English | MEDLINE | ID: mdl-36848715

ABSTRACT

Horsfiequinone G (1), a dimeric diarylpropane featuring an unprecedentedly oxo-6/7/6 fused ring system, a new flavane, horsfielenide F (2), three naturally occurring spirocyclic monomers containing all-carbon quaternary centers, horspirotone A (3), horspirotone B (4), and methyl spirobroussonin B (5), along with horsfiequinone A (6) were isolated from Horsfieldia kingii. Their structures and absolute configurations were determined by the inspection of extensive spectroscopic data and electronic circular dichroism (ECD) calculations. Biological evaluations of these isolates revealed that compounds 1 - 3 and 5 - 6 exhibited specifically immunosuppressive activities against Con A-induced T lymphocytes with IC50 values ranging from 2.07 to 12.34 µM (selectivity indices = 2.3-25.2). Compound 1 also suppressed the secretion of inflammatory factors like IL-1ß and IL-6 in RAW264.7 cells which could present a new class of nonsteroidal anti-inflammatory agent. Finally, the primary structure-activity relationship (SAR) was also discussed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Immunosuppressive Agents , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carbon , Circular Dichroism , Immunosuppressive Agents/pharmacology , Molecular Structure , Structure-Activity Relationship
6.
Chem Biodivers ; 20(3): e202201185, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36795028

ABSTRACT

Two new bibenzyl-phenylpropane hybrids, dendrophenols A and B (1 and 2), along with nine known bibenzyls, were isolated from the aerial part of Dendrobium devonianum Paxt. Their structures were determined by extensive spectroscopic methods and methylation. Bioassays revealed that compounds 1-9 were specifically immunosuppressive to T lymphocytes with IC50 values ranging from 0.41 to 9.4 µM, of which compounds 1 (IC50 =1.62 µM) and 2 (IC50 =0.41 µM) were promising immunosuppressive agents for T lymphocytes with the selectivity indices of 19.9 and 79.5, respectively.


Subject(s)
Bibenzyls , Dendrobium , Bibenzyls/pharmacology , Bibenzyls/chemistry , Dendrobium/chemistry , Free Radical Scavengers/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970586

ABSTRACT

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.


Subject(s)
Medicine, Chinese Traditional , Inventions , China , Drugs, Chinese Herbal
8.
Gut and Liver ; : 382-388, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1000376

ABSTRACT

Background/Aims@#We aimed to investigate the comfort, safety, and endoscopic visibility during esophagogastroduodenoscopy (EGD) afforded by a modified 4-hour semifluid and 2-hour water (“4+2”) fasting protocol. @*Methods@#In this parallel group, endoscopist-blinded, randomized controlled trial, outpatients undergoing unsedated diagnostic EGD from 10:30 AM to 12:00 PM were randomly assigned to either a “4+2” protocol group or a conventional fasting group. The participants’ comfort during the fasting period and procedure was measured using the visual analog scale, and mucosal visibility was measured by endoscopists using the total visibility score. Satisfaction was defined as a visual analog scale score of ≤3. The primary outcome was the participants’ comfort during fasting. @*Results@#One hundred and six and 108 participants were randomized to the “4+2” protocol and control groups, respectively. Participants’ comfort before EGD was significantly higher in the “4+2” protocol group measured by both the proportion of satisfaction (86.8% vs 63.9%, p=0.002) and the visual analog scale score (median [interquartile range]: 1.0 [1.0–2.0] vs 3.0 [1.0–4.0], p<0.001). The proportion of satisfaction during EGD also significantly improved (59.4% vs 45.4%, p=0.039) in the “4+2” protocol group. The total visibility score was unaffected by the fasting protocol (5.0 [4.0–5.0] vs 4.0 [4.0–5.0], p=0.266). No adverse events were observed during the study. @*Conclusions@#The “4+2” protocol was more comfortable and provided equal mucosal visibility and safety compared with conventional fasting for unsedated EGD.

9.
Front Chem ; 10: 1036683, 2022.
Article in English | MEDLINE | ID: mdl-36247672

ABSTRACT

The analysis of glyphosate is essential to agricultural production, environment protection and public health. Herein, we proposed a fast and convenient "on-off-on" fluorescence platform for sensitive detection of glyphosate via Cu2+ modulated g-C3N4 nanosheets. The fluorescence of the system was quenched by Cu2+. With the presence of glyphosate, the fluorescence could be restored due to the formation of Cu2+- glyphosate complex. The proposed method was cost-effective with label-free and enzyme-free. Moreover, it exhibits high sensitivity with a low detection limit of 0.01 µg/ml. Furthermore, the proposed method has been successfully monitored glyphosate in real samples.

11.
Chem Biodivers ; 19(6): e202200259, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35510718

ABSTRACT

Two new isopentenyl bibenzyls, denchrysotonols A and B (1-2), along with 26 known phenolic compounds, were isolated from the stems of cultivated Dendrobium chrysotoxum Lindl. Their chemical structures were clearly elucidated by extensive spectroscopic analysis. Biological evaluation of isolated compounds revealed that phenanthrenes (14, 16-17, 20, and 22) and fluorenone 25 exhibited anti-inflammatory activities which inhibited nitric oxide (NO) production in LPS-activated RAW264.7 macrophages with the IC50 values ranging from 9.4 to 32.5 µM. Moreover, bibenzyls (1-2 and 7) showed good anti-proliferative activities against triple-negative breast cancer (TNBC) cells (HCC1806, MDA-MB-231, and MB-MB-468) with the IC50 values ranging from 8.1 to 18.6 µM, of which 1 and 2 seemed preferentially inhibit MDA-MB-231 cells.


Subject(s)
Bibenzyls , Dendrobium , Anti-Inflammatory Agents/pharmacology , Bibenzyls/chemistry , Bibenzyls/pharmacology , Dendrobium/chemistry , Macrophages , Molecular Structure , Phenols/pharmacology
12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-940506

ABSTRACT

The pathological changes of the heart after myocardial infarction (MI) are complex, involving multiple molecular mechanisms and various cells, such as myocardial cells, endothelial cells, fibroblasts, and macrophages. With multiple targets, Chinese medicine demonstrates ideal cardioprotective effect. However, the complex mechanism of multi-component Chinese medicine formulas has not been elucidated, thus limiting the further application. The high-throughput single-cell RNA sequencing (scRNA-seq) technology offers single-cell transcriptome analysis of hundreds of drugs under different processing conditions in a single experiment and identifies the differences in the response of different cells and cell subtypes to drug treatment. scRNA-seq technology helps us to understand the exact cellular and molecular mechanisms of cardiac remodeling from acute ischemic events to chronic cardiac scarring. The application of scRNA-seq to studying the cardioprotective mechanism of Chinese medicine after MI can boost the development of Chinese medicine, help obtain richer, more accurate and comprehensive information. It can give us a clear insight into the mechanism of Chinese medicine based on complex network. In this study, we summarized the research on cardioprotective mechanism of Chinese medicine and introduced the development of scRNA-seq technology and the application to MI research. Finally, we explored the possible application prospects of scRNA-seq in the research on cardioprotective mechanism of Chinese medicine after MI, hoping to provide ideas for the modernization of Chinese medicine.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-995341

ABSTRACT

Objective:To analyze characteristics and trend of publications in digestive endoscopy quality control from 2010 to 2021.Methods:The literature on digestive endoscopy quality control from 2010 to 2021 were searched through the Web of Science core collection with the method of bibliometrics. The year of publication, journal name, country, main researchers, institutions and citations were analyzed by Web of Science. Then, the downloaded data were imported into VOSviewer for co-occurrence network analysis of the country, keywords and citations.Results:A total of 3 283 English papers on digestive endoscopy quality control were included. The number of papers from China and other countries showed an upward trend, and citations as well from 2010 to 2021. The publications were mainly from the United States (1 209, 36.8%), the United Kingdom (325, 9.9%), and China (324, 9.9%). The journal with the largest number of publications in this category was Gastrointest Endosc (241, 7.3%). The U.S. Department of Veterans Affairs had 175 publications, ranking the first among all institutions. Research topics were focused on colonoscopy, adenoma detection rate, and artificial intelligence. Conclusion:The research in digestive endoscopy quality control is booming, and the research activity is gradually increasing. Chinese academic influence in this field still needs to be further improved.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-995339

ABSTRACT

Objective:To investigate the current status of endoscopy department of county hospitals in China, and to improve the construction quality of the endoscopy department of county hospitals.Methods:County hospitals from 20 provinces, autonomous regions and municipalities in 2019 were investigated in this study through an online survey. Questions were about the department scale, basic information of the endoscopy center, clinical diagnosis and treatment ability, teaching and academic ability.Results:A total of 114 county hospitals were included. The department of gastroenterology in county hospitals owned 38.9 beds, 8.6 doctors and 6.4 nurses on average in 2019. The mean host and endoscope were 3.1 and 11.0 respectively in each center. The mean outpatient, discharge and endoscopy procedure were 22 thousand , 2.3 thousand and 7.8 thousand respectively. The referral rate of 53 (46.5%) hospitals to higher-level hospitals was less than 3%. In terms of teaching and academy, 5 (4.4%) in 114 hospitals had endoscopist training bases of Chinese Medical Association. Fifty-two (45.6%) county hospitals hosted academic conferences at the city level and above, 21 (18.4%) published SCI papers and 67 (58.8%) published papers in key Chinese journals.Conclusion:Endoscopy centers of most county hospitals are well constructed with comprehensive facilities, qualified medical ability, management, and a research team, which meets the recommendation level of service.

15.
Nat Prod Res ; 35(7): 1127-1133, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31322421

ABSTRACT

Three new diarylpropanes (1-3), including two diarylpropane glycosides, and three known ones, were isolated from 70% aqueous acetone extract of the twigs and leaves of Horsfieldia kingii. Their structures were elucidated by spectroscopic analysis. Bioactive evaluation of inhibition on DDC enzyme assay showed that the new compounds were inactive.


Subject(s)
Flavonoids/isolation & purification , Myristicaceae/chemistry , Aromatic Amino Acid Decarboxylase Inhibitors/chemistry , Aromatic Amino Acid Decarboxylase Inhibitors/pharmacology , Dopa Decarboxylase/metabolism , Flavonoids/chemistry , Flavonoids/pharmacology , Glycosides/chemistry , Glycosides/pharmacology , Humans , Plant Extracts/chemistry , Plant Leaves/chemistry , Proton Magnetic Resonance Spectroscopy
16.
Journal of Clinical Hepatology ; (12): 229-232, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-862577

ABSTRACT

Common bile duct stones (CBDSs) are a common biliary tract disease, and endoscopic therapy is the first-line treatment modality for this disease; however, some CBDSs are difficult to remove by conventional endoscopic techniques and are thus called difficult CBDSs. Therapies for difficult CBDSs include endoscopic papillary large balloon dilation, mechanical lithotripsy, choledochoscopy-assisted lithotripsy, and extracorporeal shockwave lithotripsy. This article reviews the advances in the above mentioned techniques for the treatment of difficult CBDSs, including indications, clinical effect, and adverse events.

17.
Gut and Liver ; : 262-272, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-874585

ABSTRACT

Background/Aims@#Single-balloon enteroscopy (SBE) has been widely used in diagnosing small bowel disease. We conducted this study to systematically appraise its technical and clinical performance. @*Methods@#Studies on SBE published by September 2018 were systematically searched. Technical and clinical performance data were collected and analyzed with descriptive or meta-analysis methods. @*Results@#In total, 54 articles incorporating 4,592 patients (6,036 procedures) were included. Regarding technical parameters, the pooled insertion depths (IDs) for anterograde and retrograde SBE were 209.2 cm and 98.1 cm, respectively. The pooled retrograde ID in Asian countries was significantly greater than that in Western countries (129.0 cm vs 81.1 cm, p<0.001). The pooled anterograde and retrograde procedure times were 57.6 minutes and 65.1 minutes, respectively.The total enteroscopy rate was 21.9%, with no significant difference between Asian and Western countries. Clinically, the pooled diagnostic yield of SBE was 62.3%. Obscure gastrointestinal bleeding (OGIB) was the most common indication (50.0%), with a diagnostic yield of 59.5%. Vascular lesions were the most common findings in Western OGIB patients (76.9%) but not in Asian ones (31.0%). The rates of severe and mild adverse events were 0.5% and 2.5%, respectively. @*Conclusions@#SBE is technically efficient and is clinically effective and safe, but total enteroscopy is relatively difficult to achieve with this technique. Etiologies of OGIB in Asian countries differ from those in Western countries.

18.
Nat Prod Res ; 34(3): 390-397, 2020 Feb.
Article in English | MEDLINE | ID: mdl-30600696

ABSTRACT

Twenty-seven compounds, including a new diarypropane and two new lignans were isolated from the twigs and leaves of Endocomia macrocoma. Their structures were elucidated by spectroscopic analysis. Cytotoxicity evaluation of the new compounds against five human tumor lines showed no inhibitory effects.[Formula: see text].


Subject(s)
Lignans/isolation & purification , Myristicaceae/chemistry , Propane/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Lignans/chemistry , Lignans/pharmacology , Molecular Structure , Plant Extracts/chemistry , Plant Leaves/chemistry , Propane/chemistry , Propane/pharmacology
19.
J Asian Nat Prod Res ; 22(4): 353-358, 2020 Apr.
Article in English | MEDLINE | ID: mdl-30835549

ABSTRACT

Twelve dihydrostilbenes (including five new analogues) were prepared by the Witting-Hornor reaction from appropriate aromatic aldehydes and phosphonate esters, followed by hydrogenation in five steps. The in vitro inhibition activity against human neutrophil elastase (HNE) of these dihydrostilbenes was evaluated, and three 1,2-dihydroxylated dihydrostilbenes (6b, 6j, and 6l) exhibited stronger inhibitory activity against HNE than other analogues.


Subject(s)
Dihydrostilbenoids , Leukocyte Elastase , Humans , Molecular Structure
20.
Chinese Journal of Trauma ; (12): 720-725, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-867771

ABSTRACT

Objective:To Analyze the risk factors and prognosis of patients with hyperfibrinolysis after severe trauma.Methods:A prospective case-control study was conducted to analyze the clinical data of severe trauma patients whose injury severity score (ISS)≥16 points admitted to First People's Hospital of Taicang from October 2017 to December 2018. Blood clot dissolution rate parameter (LY30) ≥3% was diagnosed as hyperfibrinolysis. The patients were divided into hyperfibrinolysis group ( n=27) and non-hyperfibrinolysis group ( n=27). Data were collected including patients' general information, hemoglobin (Hb), hematocrit (Hct), platelet count (PLT), fibrinogen (Fg), lactic acid value and thrombelastograghy (TEG). Univariate and multivariate Logistic regression analysis were used to identify risk factors of hyperfibrinolysis after severe trauma. Prognostic indicators and K-M survival curve of the patients were analyzed. Results:(1) A total of 142 patients with severe trauma were enrolled. There were 101 males and 41 females, aged 45-65 years (mean, 56 years). The incidence of hyperfibrinolysis was 14.8%. (2) Univariate analysis showed that ISS, abbreviated injury scale (AIS) ratio of pelvic limbs ≥3 points, shock index (SI) ratio >1, temperature, PLT, Fg and lactic acid value were correlated with the occurrence of hyperfibrinolysis after severe trauma ( P<0.05). (3) Multivariate Logistic regression analysis showed that PLT ( OR=1.035), ISS ( OR=0.898) and lactate acid value ( OR=0.735) were independent risk factors for hyperfibrinolysis after severe trauma ( P<0.05 or 0.01). (4) Hyperfibrinolysis group required more massive transfusion (38.1% vs. 2.5%), were more prone to multiple organ dysfunction syndrome (MODS) (90.5% vs. 48.8%), and had a higher 24-hour mortality (47.6% vs. 8.3%), when compared with non-hyperfibrinolysis group ( P<0.01). K-M survival curve indicated that the median survival time in hyperfibrinolysis group after trauma was 1.33 days ( IQR, 0.40-17.20 days). Conclusions:The incidence of hyperfibrinolysis after severe trauma is low. ISS, PLT and lactic acid value are the independent risk factors for hyperfibrinolysis after severe trauma. Patients with severe post-traumatic hyperfibrinolysis are characterized by high probabilities of massive transfusion and MODS, short survival time and high early mortality.

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