ABSTRACT
RATIONALE: Tetrandrine, the Q-marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated. METHODS: The metabolites of tetrandrine in rats were profiled using ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology. RESULTS: A total of 30 metabolites were characterized in rats after ingestion of tetrandrine (10 mg/kg), including 0 in plasma, 7 in urine, 11 in feces, 9 in liver, 8 in spleen, 4 in lung, 5 in kidney, 5 in heart, and 4 in brain. This study was the first to show the metabolic processes demethylation, hydroxylation, and carbonylation in tetrandrine. The pharmacology network results showed that tetrandrine and its metabolites could regulate AKT1, TNF, MMP9, MMP2, PAK1, and so on by involving in proteoglycan tumor pathway, PI3K-Akt signaling pathway, tumor pathway, MAPK signaling pathway, and Rap1 signaling pathway. CONCLUSIONS: The metabolism features of tetrandrine and its potential antitumor mechanism were summarized, providing data for further pharmacological validation.
Subject(s)
Drugs, Chinese Herbal , Neoplasms , Rats , Animals , Phosphatidylinositol 3-Kinases , Network Pharmacology , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistryABSTRACT
The efficient single-step purification of ethylene from ternary C2 mixtures containing ethane and acetylene is challenging and demanding. Herein, we introduce a novel cerium-based metal-organic framework (MOF) of Ce-NTB-rtk synthesized via a ligand-conformer strategy. The Ce-NTB-rtk features a rare tetranuclear cerium cluster and 2D kgd layers pillared by a 3D rtl framework concomitant with an extraordinary (3,3,12)-c network. The compound encompasses microporous cavities replete with a nonpolar microenvironment. Gas sorption and breakthrough experiments demonstrate its superior affinity for C2H6 and C2H2 over C2H4, enabling effective single-step ethylene purification. Computational simulations reveal that preferential adsorptions are facilitated by different interaction strengths of C-H···O hydrogen bonds. The performance of Ce-NTB-rtk in separation selectivity and regeneration capacity makes it a promising candidate for sustainable and cost-effective ethylene purification, showcasing the potential of MOFs in advanced gas separation applications.
ABSTRACT
Fenofibrate, a marketed peroxisome proliferator-activated receptor-α (PPARα) agonist, has been widely used for treating severe hypertriglyceridemia and mixed dyslipidemia. As a canonical prodrug, fenofibrate can be rapidly hydrolyzed to release the active metabolite (fenofibric acid) in vivo, but the crucial enzyme(s) responsible for fenofibrate hydrolysis and the related hydrolytic kinetics have not been well-investigated. This study aimed to assign the key organs and crucial enzymes involved in fenofibrate hydrolysis in humans, as well as reveal the impact of fenofibrate hydrolysis on its non-PPAR-mediated biologic activities. Our results demonstrated that fenofibrate could be rapidly hydrolyzed in the preparations from both human liver and lung to release fenofibric acid. Reaction phenotyping assays coupling with chemical inhibition assays showed that human carboxylesterase 1A (hCES1A) played a predominant role in fenofibrate hydrolysis in human liver and lung, while human carboxylesterase 2A (hCES2A) and human monoacylglycerol esterase (hMAGL) contributed to a very lesser extent. Kinetic analyses showed that fenofibrate could be rapidly hydrolyzed by hCES1A in human liver preparations, while the inherent clearance of hCES1A-catalyzed fenofibrate hydrolysis is much higher (>200-fold) than than that of hCES2A or hMAGL. Biologic assays demonstrated that both fenofibrate and fenofibric acid showed very closed Nrf2 agonist effects, but fenofibrate hydrolysis strongly weakens its inhibitory effects against both hCES2A and hNtoum. Collectively, our findings reveal that the liver is the major organ and hCES1A is the predominant enzyme-catalyzing fenofibrate hydrolysis in humans, while fenofibrate hydrolysis significantly reduces inhibitory effects of fenofibrate against serine hydrolases. SIGNIFICANCE STATEMENT: Fenofibrate can be completely converted to fenofibric acid in humans and subsequently exert its pharmacological effects, but the hydrolytic pathways of fenofibrate in humans have not been well-investigated. This study reported that the liver was the predominant organ and human carboxylesterase 1A was the crucial enzyme involved in fenofibrate hydrolysis in humans.
ABSTRACT
Due to their intrinsic structural features, the design and synthesis of a new type of zeolite-like metal-organic frameworks (ZMOFs) is highly desirable but challenging. Herein, solvothermal reactions between an angular dicarboxylate linker and rare-earth (RE) ions afforded two RE-MOFs, namely, Tb-ZMOF-2 and Tb-ZMOF-3, respectively. Structural analyses reveal that Tb-ZMOF-2 encompasses a novel [446482] cage, while Tb-ZMOF-3 contains nonanuclear (i.e., D6R) and hexanuclear (i.e., D4R) RE clusters simultaneously, subsequently resulting in two new zeolitic topologies. Thanks to its high surface area and pore volume, Tb-ZMOF-2 demonstrates considerably high gravimetric and volumetric methane storage working capacities.
ABSTRACT
OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Subject(s)
Caffeine , Respiration, Artificial , Caffeine/therapeutic use , Citrates , Humans , Infant , Infant, Newborn , Infant, Premature , Retrospective StudiesABSTRACT
In pursuit of novel adsorbents with efficient adsorptive gas storage and separation capabilities remains highly desired and challenging. Although the documented zirconium-tricarboxylate-based metal-organic frameworks (MOFs) have displayed a variety of topologies encompassing underlying and geometry mismatch ones, the employed organic linkers are exclusively rigid and poorly presenting one type of conformation in the resultant structures. Herein, a used and semirigid tricarboxylate ligand of H3 TATAB was judiciously selected to isolate a zirconium-based spe-MOF after the preliminary discovery of srl-MOF. Single-crystal X-ray diffraction reveals that the fully deprotonated TATAB linker in spe-MOF exhibits two distinct conformers, concomitant with popular Oh and rare S6 symmetrical Zr6 molecular building blocks, generating an unprecedented (3,3,12,12)-c nondefault topology. Specifically, the spe-MOF exhibits structurally higher complexity, hierarchical micropores, open metal sites free and rich electronegative groups on the pore surfaces, leading to relatively high methane storage capacity without considering the missing-linker defects and efficient MTO product separation performance.
ABSTRACT
A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced ß-amyloid (Aß) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7â¯nM for hAChE and 0.66⯵M for hBuChE) and the good Aß aggregation inhibition (49.2% at 20⯵M), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Aß-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation.
Subject(s)
Alzheimer Disease/drug therapy , Anticoagulants/therapeutic use , Coumaric Acids/chemistry , Coumaric Acids/chemical synthesis , Molecular Docking Simulation/methods , Alzheimer Disease/pathology , Anticoagulants/pharmacology , Drug Design , Humans , Ligands , Models, MolecularABSTRACT
The epigenetic effects on expression of non-coding RNAs (e.g. microRNAs) of environmental toxin bisphenol A (BPA) have extended our understanding of the etiology of human reproductive disorders including hypospermatogenesis and androgen deficiency. BPA-induced miR-146a-5p is a potent regulator of endocrine and immune homeostasis, but its role in testis remain unexplored. We show here that in murine testis, miR-146a-5p was exclusively expressed in interstitial Leydig cells (LCs). This expression was significantly induced by BPA exposure. Consequently, the elevated miR-146a-5p exacerbated the deleterious effects of BPA on testicular steroidogenesis. Mechanistically, miR-146a-5p repressed the expression of Mta3, a pivotal chromatin remodeling transcription factor recently involved in controlling the steroidogenic activity, via directly targeting its 3'UTR. This repression thereafter rendered LCs more sensitive to BPA-elicited inhibitory effects. Conversely, ectopic expression of hMTA3 successfully rescued miR-146a-5p-elicited inhibitory effects on testicular steroidogenesis in BPA-challenged LCs. Taken together, the available data provide novel evidence that deregulation of testicular miR-146a-5p/Mta3 cascade mediates, at least in part, the steroidogenic dysfunction caused by BPA exposure.
Subject(s)
Benzhydryl Compounds/adverse effects , Gene Expression Regulation/drug effects , MicroRNAs/genetics , Neoplasm Proteins/genetics , Phenols/adverse effects , Signal Transduction/drug effects , Steroids/metabolism , Testis/drug effects , 3' Untranslated Regions/drug effects , Animals , Epigenesis, Genetic/drug effects , Leydig Cells/drug effects , Leydig Cells/metabolism , Male , Mice , Mice, Inbred C57BL , Neoplasm Proteins/metabolism , Testis/metabolismABSTRACT
Although both insulin and estrogen receptor α (ERα) are known to exert inhibitory effects on testicular steroidogenesis, it remains unknown whether these pathways regulate testosterone (T) production under certain pathological conditions [e.g., type 2 diabetes mellitus (T2DM)] in a coordinated manner. Here, we found that the expression of forkhead box protein A3 (Foxa3), an essential transcriptional regulator engaged in adipogenesis and energy metabolism, was significantly down-regulated in the Leydig cells (LCs) from T-deficient T2DM mice. Functionally, upon hCG stimulation, Foxa3 recruits to the Esr1 promoter and suppresses the transactivation of Esr1 gene. Disruption of this recruitment by T2DM-elicited hyperinsulinemia led to abnormal activation of ERα pathway, inhibited steroidogenic enzyme genes expression, and thus caused inadequate T production. Therapeutically, insulin-impaired and Foxa3 ablation-compromised steroidogenesis were effectively rescued by a pharmacological inhibitor of the ERα pathway. These findings reveal an obligatory coregulatory role of Foxa3 in the regulation of ERα expression and of the Foxa3/ERα cascade, at least in part, in the pathogenesis of androgen deficiency caused by T2DM.
Subject(s)
Diabetes Mellitus, Type 2/metabolism , Estrogen Receptor alpha/metabolism , Hepatocyte Nuclear Factor 3-gamma/metabolism , Leydig Cells/metabolism , Signal Transduction , Testosterone/metabolism , Animals , Cells, Cultured , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Down-Regulation , Estrogen Receptor alpha/genetics , Hepatocyte Nuclear Factor 3-gamma/genetics , Leydig Cells/pathology , Male , Mice, Inbred BALB C , Steroids/metabolism , Transcriptional ActivationABSTRACT
Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD50) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application.
Subject(s)
Alkaloids , Plant Extracts , Animals , Mice , Ethnopharmacology , Plant Extracts/chemistry , Medicine, Chinese Traditional , Anti-Inflammatory Agents , PhytochemicalsABSTRACT
Background: The frequent exacerbator phenotype of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is characterized by experiencing at least two exacerbations per year, leading to a significant economic burden on healthcare systems worldwide. Although several biomarkers have been shown to be effective in assessing AECOPD severity in recent years, there is a lack of studies on markers to predict the frequent exacerbator phenotype of AECOPD. The current study aimed to develop a new predictive model for the frequent exacerbator phenotype of AECOPD based on rapid, inexpensive, and easily obtained routine markers. Methods: This was a single-center, retrospective study that enrolled a total of 2,236 AECOPD patients. The participants were divided into two groups based on the frequency of exacerbations: infrequent group (n=1,827) and frequent group (n=409). They underwent a complete blood count, as well as blood biochemistry, blood lipid and coagulation testing, and general characteristics were also recorded. Univariate analysis and binary multivariate logistic regression analyses were used to explore independent risk factors for the frequent exacerbator phenotype of AECOPD, which could be used as components of a new predictive model. The receiver operator characteristic (ROC) curve was used to assess the predictive value of the new model, which consisted of all significant risk factors predicting the primary outcome. The nomogram risk prediction model was established using R software. Results: Age, gender, length of stay (LOS), neutrophils, monocytes, eosinophils, direct bilirubin (DBil), gamma-glutamyl transferase (GGT), and the glucose-to-lymphocyte ratio (GLR) were independent risk factors for the frequent exacerbator phenotype of AECOPD. The area under the curve (AUC) of the new predictive model was 0.681 [95% confidence interval (CI): 0.653-0.708], and the sensitivity was 63.6% (95% CI: 58.9-68.2%) and the specificity was 65.0% (95% CI: 60.3-69.6%). Conclusions: A new predictive model based on demographic characteristics and blood parameters can be used to predict the frequency of acute exacerbations in the management of chronic obstructive pulmonary disease (COPD).
ABSTRACT
Due to the industrial requirements for high production and high quality of ethylene, efficient purification of ethylene from acetylene and ethane is of prime importance but challenging. Dynamic metal-organic frameworks (MOFs) have demonstrated intriguing structural dynamics and diverse applications recently. Among them, although a few flexible ones have exhibited interesting ethylene purification capability, rigid ones were yet barely investigated for such purpose. In this regard, a cerium(III)-based MOF was solvothermally synthesized, which is rigid and assembled from rod molecular building blocks associated with coordinative N,N-dimethylformamide (DMF) molecules. After liberating different degrees of DMF ligands via heating under vacuum or acetone exchange, both partially desolvated compounds of Ce-MOF-1 and Ce-MOF-2 were concertedly isolated in a fashion of single-crystal to single-crystal transformation. Although both newly generated materials crystallize in the same space group, they exhibit dissimilar unit cell parameters and slightly distinct ultramicropore sizes and pore microenvironments, thanks to the discrepancy in the desolvation degree. Consequently, Ce-MOF-1 and Ce-MOF-2 individually demonstrate C2H2- and C2H6-selective adsorption behavior, resulting in the potential tandem separation of C2H4 from C2H2 and C2H6 mixtures. The above results were successfully supported by not only single gas adsorption isotherms but also grand canonical Monte Carlo (GCMC) calculation studies and dynamic breakthrough experiments. The present work may pave the way for rigid MOFs aiming at advancing applications via solid-state structural dynamics.
ABSTRACT
Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed Km values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Carboxylesterase/metabolism , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Alanine/chemistry , Alanine/metabolism , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Carboxylesterase/chemistry , Cathepsin A/chemistry , Cathepsin A/metabolism , Humans , Hydrolysis/drug effects , Kinetics , Liver/metabolism , Microsomes, Liver/metabolism , Simvastatin/pharmacologyABSTRACT
CASE SUMMARY: A patient who underwent mechanical aortic and mitral valve replacement developed three paravalvular leaks 10 months later. We located the tracks by puncturing the apex cordis under transoesophageal echocardiography guidance alone and puncturing the femoral artery guided by fluoroscopy. Three paravalvular leaks were occluded with a hybridization method simultaneously. The patient was followed up for 24 months and maintained a good condition. CONCLUSION: Multiple paravalvular leaks after double valve replacement can be occluded in patients by the use of different approaches under echocardiographic guidance alone.
Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Cardiac Catheterization , Echocardiography , Echocardiography, Transesophageal , HumansABSTRACT
Cancer-derived exosomes or their specific components hold great promise for early diagnosis and precise staging of cancers. This work aimed to construct a novel enzyme-activatable fluorescent substrate for real-time detection and in situ imaging of a key exosomal surface protein CD26 in various biological systems, as well as to reveal the relevance of exosomal CD26 to the tumorigenesis. For these purposes, a group of Gly-Pro amides deriving from several near-infrared fluorophores were designed on the basis of the unique prolyl-cleaving dipeptidease activity of CD26, while molecular docking simulations were applied to assess the possibility of the designed amides as CD26 specific substrates. Following virtual screening and experimental validation, it was observed that GP-ACM displayed the best combination of high sensitivity and excellent specificity to CD26. The sensing and imaging ability of GP-ACM towards CD26 were examined in a range of biological systems, such as living cells, in situ tissues, and the exosomes secreted from cancer cells. Under physiological conditions, GP-ACM can be readily hydrolyzed by CD26 to release the fluorescent product ACM. The fluorescent product emits strong near-infrared fluorescence signals around 660 nm, which can be easily captured by the devices equipped with a fluorescence detector. GP-ACM prolyl-cleaving reaction shows excellent specificity and rapid response towards CD26, while its fluorescent product ACM displays good chemical stability and outstanding photostability. With the help of GP-ACM, CD26 in living cells, tissues and the tumor-secreted exosomes can be real-time monitored and in-situ imaged, while further investigations reveal that the exosomal CD26 activities are abnormally elevated with the progression of colon tumor. Collectively, the present study offers a practical optical assay for real-time monitoring CD26 activities in multiple complex biological systems including the exosomes secreted by tumor cells. The simplicity and effectiveness of this assay hold great potential for facilitating fundamental researches and clinical diagnosis of exosomal CD26 associated diseases.
Subject(s)
Colorectal Neoplasms , Exosomes , Colorectal Neoplasms/diagnostic imaging , Dipeptidyl Peptidase 4 , Fluorescent Dyes , Humans , Molecular Docking SimulationABSTRACT
In the title compound, C(11)H(15)N(5)O(2), the 1,3,5-triazine ring exhibits a half-chair conformation. An intra-molecular N-Hâ¯O inter-action occurs. In the crystal structure, mol-ecules are connected by inter-molecular C-Hâ¯O and N-Hâ¯N hydrogen bonds, forming a zigzag chain along the b axis.
ABSTRACT
In the title compound, C(14)H(11)Cl(2)N(3)S, the thia-zole ring is in an envelope conformation with the -CH(2)- group bonded to the S atom forming the flap. The crystal structure is stabilized by weak inter-molecular C-Hâ¯Cl and C-Hâ¯N hydrogen bonds.
ABSTRACT
The title compound, C(12)H(12)ClN(3)S, features a thia-zolyl ring having an envelope conformation with the -CH(2)- group bonded to the S atom forming the flap. The C=N double bond has a Z configuration. The crystal structure shows inter-molecular C-Hâ¯S hydrogen bonds.
ABSTRACT
OBJECTIVE: In order to improve accuracy of forensic expert conclusion and provide scientific and reasonable accordance for revising identifying criteria for the injury degree, correlation between clinical classification and injury certification of acute closed head trauma were explored. METHODS: A total of 30 cases about acute closed head trauma were selected. Comparison and analysis were made about their differences and the correlation between the clinical classification and the injury degree certification. RESULTS: Mild craniocerebral injury is equal to mild or moderate injury, moderate craniocerebral injury is equivalent to mild or severe injury, severe craniocerebral injury is mostly equivalent to severe injury. CONCLUSION: There are some correlation between the clinical classification and the injury certification in acute closed head trauma. It is necessary to refer to the criteria of clinical classification when revising identifying criteria for the injury degree so as to enhance scientific rigor and rationality.
Subject(s)
Expert Testimony/standards , Head Injuries, Closed/diagnosis , Injury Severity Score , Adult , Brain Concussion/etiology , Brain Concussion/pathology , Female , Forensic Pathology/standards , Head Injuries, Closed/classification , Head Injuries, Closed/pathology , Humans , Male , Middle Aged , Retrospective Studies , Subarachnoid Hemorrhage/etiology , Subarachnoid Hemorrhage/pathology , Young AdultABSTRACT
Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 term-born infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital (approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016409) and the protocol version is 1.0.