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BACKGROUND: Strain echocardiography (SE) is a procedure for analyzing myocardial dysfunction that is known to be less dependent on preload and afterload of heart function. Unlike dimension-based parameters, like ejection fraction (EF) and fractional shortening (FS), SE measures cardiac function by tracking cardiac tissue deformation and anomalies throughout the cardiac cycle. Although SE is proven to locate myocardial ailments in various heart diseases, few studies exist regarding using SE relevant to sepsis pathophysiology. OBJECTIVE: The study aimed to calculate the myocardial strain and strain rates, like longitudianl strain (LS), global radial strain (GRS), and global longitudinal strain (GLS), and to show these to be reduced earlier in cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)-induced sepsis in coordination with an elevation of pro-inflammatory cytokines Methodology: Wild-type mice C57BL/6J (WT) were taken in this study and classified as CLP, LPS, and control groups. CLP surgery and LPS injection were given to induce sepsis. Endotoxemic septic shock was induced by intraperitoneal (IP) injection of LPS Escherichia coli. Echocardiography short axis views (SAX), longitudinal strain (LS), global circumferential strain (GCS), and global radial strain (GRS) were measured from the anterior and posterior positions of the septal and lateral walls of the heart. Real-time polymerase chain reaction (RT-PCR) was performed to evaluate post-CLP and LPS to analyze cardiac pro-inflammatory cytokines expressions. Inter- and intra-observer variables were tested by Bland-Altman analyses (BA). All data analysis was performed by GraphPad Prism 6 software. p<0.05 was taken as statistically significant. RESULT: After 48 hours following CLP and LPS-induced sepsis, a significant declination in both longitudinal strain and strain rate (LS and LSR) was identified in the CLP and LPS groups compared to the control group. Strain depression in sepsis was linked with the up-regulation of pro-inflammatory cytokines in RT-PCR analysis. CONCLUSION: In the present study, we found myocardial strain and strain rate parameters, like LS, GRS, and GLS, to be reduced after CLP and LPS-induced sepsis in coordination with the elevation of pro-inflammatory cytokines.
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Objective: To investigate the protective effect and its possible mechanism of A-kinase anchored protein 1 (AKAP1) on the myocardial injury induced by highland hypobaric hypoxia. Methods: From January 2021 to May 2022, male C57BL/6 SPF grade mice were divided into wild type control (WT) group and highland hypobaric hypoxia (HH) group with 6 mice in each group. HH group simulated 6000 m altitude with low pressure oxygen chamber for 4 weeks to build the model. Primary myocardial cells of SD rats were divided into normoxia control group and hypoxia experimental group (n=3). Cell models were constructed in a three-gas hypoxia incubator with 1% oxygen concentration for 24 h. AKAP1 protein and mRNA expression in myocardial tissue and cells were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). After myocardial point injection of the AKAP1 or the control adenovirus, the mice were divided into 3 groups (n=6) : WT group, highland hypobaric hypoxia overexpression control group (HH+Ad-Ctrl group) and highland hypobaric hypoxia overexpression experimental group (HH+Ad-AKAP1 group). The cardiac function of mice was detected by noninvasive M-type ultrasonic cardiomotive, myocardial fibrosis was detected by Masson and Sirius Red staining, and cardiomyocyte hypertrophy was detected by wheat germ agglutinin. After the expression of AKAP1 in primary cardiomyocytes was downregulated by siRNA and upregulated by adenovirus, the cells were divided into three groups (n=3) : normoxia control group, hypoxia interference control group (hypoxia+siCtrl group), hypoxia AKAP1 knockdown group (hypoxia+siAKAP1 group) ; normoxia control group, hypoxia overexpression control group (hypoxia+Ad-Ctrl group), hypoxia AKAP1 overexpression group (hypoxia+Ad-AKAP1 group). Apoptosis was detected by flow cytometry, AKAP1, apoptosis-related protein and mRNA expression levels were detected by western blotting and qPCR, mitochondrial membrane potential was detected by JC-1 staining, and mitochondrial reactive oxygen specie (ROS) level was detected by MitoSOX. Results: The expression of AKAP1 in cardiac muscle of HH group was lower than that in the WT group, and the expression of AKAP1 in hypoxia experimental group was lower than that in normoxia control group (P<0.01). Compared with WT group, the left ventricular ejection fraction and fraction shortening of left ventricle in HH+Ad-Ctrl group were decreased (P<0.01), myocardial fibrosis and hypertrophy were aggravated (P<0.01), and the expression of B-cell lymphoma-2 (BCL-2) was decreased, the expressions of BCL-2-associated X protein (BAX), Caspase 3 and Caspase 9 were increased (P<0.01). After AKAP1 overexpression, compared with HH+Ad-Ctrl group, the left ventricular ejection fraction and left ventricular fraction shortening were increased in HH+Ad-AKAP1 group (P<0.01), myocardial fibrosis and hypertrophy were reduced (P<0.01), and the expression of BCL-2 was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.01). Compared with normoxia control group, the expression of BCL-2 in hypoxia+siCtrl group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), the mitochondrial membrane potential was decreased and the production of ROS was increased (P<0.01). After AKAP1 knockdown, compared with hypoxia+siCtrl group, the expression of BCL-2 in hypoxia+siAKAP1 group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), mitochondrial membrane potential was decreased, and the production of ROS was increased (P<0.01). After AKAP1 overexpression, compared with hypoxia+Ad-Ctrl group, the expression of BCL-2 in hypoxia+Ad-AKAP1 group was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.05), the apoptosis level was decreased (P<0.01), and the mitochondrial membrane potential was enhanced, and the production of ROS was decreased (P<0.01) . Conclusion: The downregulation of AKAP1 in cardiomyocytes under highland hypobaric hypoxia may lead to the decrease of mitochondrial membrane potential and the increase of ROS generation, leading to the apoptosis of cardiomyocytes, and thus aggravating the myocardial injury at highland hypobaric hypoxia.
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Objective:To establish a mortality risk prediction model of severe bacterial infection in children and compare it with the pediatric early warning score (PEWS), pediatric critical illness score (PCIS) and pediatric risk of mortality score Ⅲ (PRISM Ⅲ).Methods:A total of 178 critically ill children were selected from the PICU of the Children's Hospital of Nanjing Medical University from May 2017 to June 2022. After obtaining the informed consent of the parents/guardians, basic information such as sex, age, height and weight, as well as indicators such as heart rate, systolic blood pressure and respiratory rate were collected from all children. A standard questionnaire was used to score the child 24 h after admission to the PICU. The children were divided into the survival and death groups according to their survival status at 28 d after admission. A mortality risk prediction model was constructed and nomogram was drawn. The value of the mortality risk prediction model, PEWS, PCIS and PRISM in predicting the risk of death was assessed and compared using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC).Results:Among the 178 critically ill children, 11 cases were excluded due to severe data deficiencies and hospitalization not exceeding 24 h. A total of 167 children were included in the analysis, including 134 in the survival group and 33 in the death group. A mortality risk prediction model for children with severe bacterial infection was constructed using pupillary changes, state of consciousness, skin color, mechanical ventilation, total cholesterol and prothrombin time. ROC curve analysis showed that the AUCs of mortality risk prediction model was 0.888 ( P<0.05). The AUCs of PEWS, PCIS and PRISM Ⅲ in predicting death in children with severe bacterial infection were 0.769 ( P< 0.05), 0.575 ( P< 0.05) and 0.759 ( P< 0.05), respectively. Hosmer-Lemeshow goodness-of-fit test showed the best agreement between risk of death and PEWS predicted morbidity and mortality and actual morbidity and mortality (χ 2 = 5.180, P = 0.738; χ 2 = 4.939, P = 0.764), and the PCIS and PRISM Ⅲ predicted mortality rates fitted reasonably well with actual mortality rates (χ 2= 9.110, P= 0333; χ 2 = 8.943, P= 0.347). Conclusions:The mortality risk prediction model for predicting the death risk has better prognostic value than PEWS, PCIS and PRISM Ⅲ for children with severe bacterial infection.
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Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.
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Professional esports athletes spend a long time in the same sitting posture during training and competition. Mobile esports may exacerbate potential postural problems because of the closer and unsupported arms and because athletes spend more time in a forward-/flexed-head posture. Prolonged sitting in these postures carries significant health risks and may lead to musculoskeletal problems and injuries. The objective of this retrospective study is to assess the posture, mobility, and stability of the spine for professional mobile esports athletes. We collected spine-assessment data from 48 athletes participating in a top-tier league on a real-time-strategy battle-arena online game. The spinal assessment was conducted using the SpinalMouse® under upright standing and trunk flexion in addition to the Matthiass test. Measurements were converted into Idiag Scores by the SpinalMouse® software. The Idiag Posture, Idiag Mobility, and Idiag Stability scores were 62.50 (IQR: 21), 63.50 (IQR: 19.5), and 54.50 (IQR: 14.5), respectively, and were significantly lower (p < 0.001) than the reference normative value (100). Age was found to have a weak positive correlation with the posture score (ρ = 0.29, p = 0.048). Although career duration appeared to lower the scores, the association was insignificant (p > 0.05). The scores also had no significant association with body height, body mass, body mass index, and esports team (p > 0.05). It was anticipated that mobile-based esports would attenuate the biomechanics of the spine and increase the likelihood of musculoskeletal problems, such as neck and back pain.
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BACKGROUND: Mobile-gaming athletes sit in the same posture for prolonged periods, contributing to significant health risks. This study investigated the health profiles, fatigue, pain and complaints, and musculoskeletal problems of full-time mobile-gaming athletes. METHODS: A total of 50 elite mobile-gaming athletes were involved in this study. They were the starting lineup players from all ten professional teams competing in a top-tier multiplayer online battle arena tournament. A survey was conducted to evaluate their fatigue patterns, pain levels, and complaints. A descriptive analysis was conducted to evaluate the athletes' health profiles [body mass index (BMI), fat ratio], fatigue, number of complaints, and musculoskeletal problems. The associations of career duration with BMI, fat ratio, and the total number of confirmed injuries were then determined using Spearman's rank correlation test. RESULTS: A total of 46% and 44% of the participants felt tired frequently and occasionally, while 34% and 58% experienced eyestrain frequently and occasionally, respectively. More than 30% of the participants reported headache and rhinitis. A longer esports career duration was associated with a reduction in BMI (r = -0.272, p = 0.056). Career duration had no significant association with smoking habits (p = 0.666), alcohol habits (p = 0.655), coffee habits (p = 0.946), rounds of games for which the player could maintain concentration (p = 0.253), ease of eyestrain (p = 0.569), tiredness (p = 0.510), dizziness (p = 0.071), or leg numbness (p = 0.318). CONCLUSION: The findings of this study stress the significance of esports injuries and indicate preventive measures for both athletes and recreational players.
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A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.
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Animais , Camundongos , Ácidos e Sais Biliares , Colestase/tratamento farmacológico , Cromatografia Líquida , Medicina Tradicional Tibetana , MetabolômicaRESUMO
To study the protective effect of Ershiwuwei Zhenzhu Pills on ischemic stroke rats. Ninety 4-weeks-old SPF male SD rats were randomly divided into 6 groups(n=15):sham operation group, model group, nimodipine group(12 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills high-dose group(400 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills medium-dose group(200 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills low-dose group(100 mg·kg~(-1)).The permanent middle cerebral artery occlusion model(PMCAO) was established in the model group, nimodipine group, and Ershiwuwei Zhenzhu Pills groups by the improved thread plug method, while the sham operation group did not insert the thread plug.Nimodipine group and Ershiwuwei Zhenzhu Pills groups were given intragastric administration once a day for 24 days before the modeling operation, and once 1 hour before the modeling operation, while sham operation group and model group were given equal volumes of distilled water.The neuroethology of the surviving rats was measured; The volume of cerebral infarction in rats was measured by TTC method; The histopathology of rat brain was observed by HE method; The expression levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA),superoxide dismutase(SOD) and catalase(CAT) in serum were detected by ELISA;The mRNA expressions of Notch 1,Jagged 1,Hes 1 and Bcl-2 in rat brain were detected by RT-PCR;Western blot was used to detect the expression levels of caspase-3 protein in rat brain; the expression levels of vascular endothelial growth factor(VEGF) and CD34 positive cells in rat brain were detected by immunofluorescence.The low, medium and high dose groups of Ershiwuwei Zhenzhu Pills and nimodipine group could significantly reduce the neurobehavioral score and cerebral infarction volume of rats with permanent middle cerebral artery occlusion, reduce the morphological changes of nerve cells, decrease the expression of TNF-α,IL-1β and IL-6 in rat serum, increase the activity of SOD and CAT,and reduce the level of MDA.Furthermore, the expression levels of Notch l, Jagged l, Hes l and Bcl-2 mRNA were significantly increased, and the expression level of caspase-3 protein was decreased.Meanwhile, the number of VEGF and CD34 positive cells increased in the treatment group.The differences were statistically significant. Ershiwuwei Zhenzhu Pills has a protective effect on ischemic stroke rats, and its mechanism may be related to anti-inflammation, anti-oxidation, promotion of nerve cell proliferation, inhibition nerve cell apoptosis and promotion of angiogenesis.
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Animais , Masculino , Ratos , Caspase 3/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Interleucina-6/metabolismo , AVC Isquêmico/tratamento farmacológico , Nimodipina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.
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Animais , Camundongos , Cloreto de Alumínio/efeitos adversos , Doença de Alzheimer/tratamento farmacológico , Galactose/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/metabolismo , Camundongos Endogâmicos BALB C , Extratos Vegetais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas tauRESUMO
This study aims to investigate the mechanism of the Tibetan medicine Ershiwuwei Shanhu Pills(ESP) in improving scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway. ICR mice were randomized into blank group, model group, low-dose(200 mg·kg~(-1)), medium-dose(400 mg·kg~(-1)), and high-dose(800 mg·kg~(-1)) ESP groups, and donepezil hydrochloride group. The learning and memory impairment was induced in mice by intraperitoneal injection of scopola-mine. The learning and memory abilities of mice were detected by Morris water maze test, and the damage of hippocampal neurons and cortical neurons was detected based on Nissl staining. The expression of neuron specific nuclear protein(NeuN) in hippocampus and cortex of mice was determined by immunofluorescence assay, and the content of acetylcholine(Ach) and the activity of acetylcholines-terase(AchE) in hippocampus of mice by kits. Moreover, the content of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in serum of mice was detected. The content of Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase 1(HO-1) in hippocampus was determined by Western blot. The results showed that there were significant differences in the trajectory map of mice among different groups in the behavioral experiment. Moreover, the latency of ESP groups decreased significantly compared with that in the model group. The hippocampal neurons in the high-dose ESP group were significantly more than those in the model group and the cortical neurons in the high-dose and medium-dose ESP groups were significantly more than those in the model group. The expression of NeuN in the model group was significantly decreased compared with that in the blank group, and the expression in the ESP groups was significantly higher than that in the model group. The AchE activity and MDA level were significantly decreased, and Ach content and levels of SOD, CAT, and T-AOC in the ESP groups were significantly increased in the ESP groups compared with those in the model group. The expression of Keap1 in the model group was significantly increased compared with that in the blank group, and the Keap1 expression increased insignificantly in ESP groups compared with that in the model group. The expression of Nrf2 and HO-1 was significantly lower in the model group than in the blank group, and the expression was significantly higher in the medium-dose ESP group than in the model group. In conclusion, ESP protected mice against the scopolamine-induced learning and memory impairment by regulating the Keap1/Nrf2/HO-1 signaling pathway.
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Animais , Camundongos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Medicina Tradicional Tibetana , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Extratos Vegetais , Escopolamina/efeitos adversos , Transdução de Sinais , Superóxido Dismutase/metabolismoRESUMO
The quality control and evaluation methods of Schizonepeta tenuifolia were established by HPLC fingerprint, multi index component content determination and chemical pattern recognition to provide basis for the quality control of medicinal materials. The chemical components of 25 batches of Schizonepeta tenuifolia panicle medicinal materials and decoction pieces collected were analyzed by high performance liquid chromatography, and the common pattern of fingerprint was established. A total of 22 common chromatographic peaks were calibrated, and their similarity was more than 0.9. The samples were divided into three categories according to different producing areas by cluster analysis. The results of principal component analysis and cluster analysis were consistent. Finally, five differential markers of different batches of Schizonepeta tenuifolia were selected by orthogonal partial least squares discriminant analysis. Through the identification of the reference substance, it was determined that peak 9 was hesperidin, peak 10 was rosmarinic acid, peak 13 was tilianin, peak 14 was quercetin, and peak 20 was pulegone. The quality evaluation method established in this study is stable and reliable, and is suitable for the quality control of Schizonepeta tenuifolia.
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Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.
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Humanos , Barreira Hematoencefálica , Encéfalo , Doenças do Sistema Nervoso Central , Medicina Tradicional Tibetana , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.
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Animais , Masculino , Camundongos , Modelos Animais de Doenças , Microbioma Gastrointestinal , Fígado , Medicina Tradicional Tibetana , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológicoRESUMO
The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.
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Animais , Camundongos , Acetaminofen/toxicidade , Antioxidantes/farmacologia , Glutamato-Cisteína Ligase/farmacologia , Glutationa , Interleucina-6/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado , Medicina Tradicional Tibetana , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Objective To study the genetic polymorphism of whole mitochondrial DNA (mtDNA) genomes in She population in Zhejiang and to explore the maternal genetic structure of the She population. Methods Whole mtDNA genomes of 231 unrelated individuals from She population in Zhejiang Province were sequenced. The number of mutations and population genetics parameters such as, the haplotype diversity (HD), discrimination power (DP), and random match probabilities (RMP) were analyzed. The mtDNA haplogroups of Zhejiang She population were classified, and the maternal genetic relationships between She and nine other Chinese populations were estimated. Results In 231 Zhejiang She samples, 8 507 mutations (702 types) were observed and the samples were classified into 94 haplogroups. The HD, DP and RMP values were 0.998 6, 0.994 2 and 0.005 8, respectively. The lowest genetic differentiation degree (Fst=0.006 89) was detected between Zhejiang She population and southern Han population. Principal component analysis (PCA) and median-joining network analysis showed that the genetic distance of Zhejiang She population with Guangxi Yao, Yunnan Dai and Southern Han populations was relatively close, but the population still had some unique genetic characteristics. Conclusion The whole mtDNA genomes are highly polymorphic in Zhejiang She population. The Zhejiang She population contains complex and diverse genetic components and has a relatively close maternal genetic relationship with Guangxi Yao, Yunnan Dai and Southern Han populations. Meanwhile, Zhejiang She population has kept its unique maternal genetic components.
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Humanos , Povo Asiático/genética , China , DNA Mitocondrial/genética , Etnicidade/genética , Genética Populacional , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo GenéticoRESUMO
OBJECTIVE@#To study the clinical features of children with adenovirus pneumonia and hemophagocytic lymphohistiocytosis (HLH).@*METHODS@#A retrospective analysis was performed on the mediacal data of 7 children with adenovirus pneumonia and HLH from March to September, 2019.@*RESULTS@#The age of these children ranged from 11 months to 5 years, and among these children, 5 were aged <2 years and 5 were boys. None of these children had underlying diseases. All children were hospitalized due to persistent high fever and cough, and the peak temperature of fever was 39°C to 41°C. With disease progression, 7 children developed hepatomegaly and 6 developed splenomegaly. Routine blood test results showed reductions in two or three lineages of blood cells, with increases in serum ferritin (SF), C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH). Phagocytosis of blood cells was observed in 6 children. Radiological examination of lungs showed pneumonia changes. All 7 children were diagnosed with human adenovirus type 7 infection based on pathogenic metagenome detection. No abnormality was found by HLH gene detection and the children were diagnosed with secondary HLH. All children received intravenous immunoglobulin. Among these children, 4 received dexamethasone and etoposide chemotherapy, 3 received dexamethasone alone, and 4 received plasma exchange. Of the 7 children, 2 died and 5 were recovered. Compared with those who survived, the children who died had significantly greater reductions in the three lineages of blood cells and significantly greater increases in serum levels of CRP, PCT, SF, and LDH.@*CONCLUSIONS@#The children with adenovirus pneumonia and HLH have main clinical features of persistent high fever, progressive reductions in two or three lineages of peripheral blood cells, and involvement of other organ systems, including hepatosplenomegaly. Significant increases in serum levels of CRP, PCT, SF, and LDH may suggest a poor prognosis.
Assuntos
Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adenoviridae , Etoposídeo , Imunoglobulinas Intravenosas , Linfo-Histiocitose Hemofagocítica , Estudos RetrospectivosRESUMO
OBJECTIVE: Radiomics pipelines have been developed to extract novel information from radiological images, which may help in phenotypic profiling of tumours that would correlate to prognosis. Here, we compared two publicly available pipelines for radiomics analyses on head and neck CT and MRI in nasopharynx cancer (NPC). METHODS AND MATERIALS: 100 biopsy-proven NPC cases stratified by T- and N-categories were enrolled in this study. Two radiomics pipeline, Moddicom (v. 0.51) and Pyradiomics (v. 2.1.2) were used to extract radiomics features of CT and MRI. Segmentation of primary gross tumour volume was performed using Velocity v. 4.0 by consensus agreement between three radiation oncologists. Intraclass correlation between common features of the two pipelines was analysed by Spearman's rank correlation. Unsupervised hierarchical clustering was used to determine association between radiomics features and clinical parameters. RESULTS: We observed a high proportion of correlated features in the CT data set, but not for MRI; 76.1% (51 of 67 common between Moddicom and Pyradiomics) of CT features and 28.6% (20 of 70 common) of MRI features were significantly correlated. Of these, 100% were shape-related for both CT and MRI, 100 and 23.5% were first-order-related, 61.9 and 19.0% were texture-related, respectively. This interpipeline heterogeneity affected the downstream clustering with known prognostic clinical parameters of cTN-status and GTVp. Nonetheless, shape features were the most reproducible predictors of clinical parameters among the different radiomics modules. CONCLUSION: Here, we highlighted significant heterogeneity between two publicly available radiomics pipelines that could affect the downstream association with prognostic clinical factors in NPC. ADVANCES IN KNOWLEDGE: The present study emphasized the broader importance of selecting stable radiomics features for disease phenotyping, and it is necessary prior to any investigation of multicentre imaging datasets to validate the stability of CT-related radiomics features for clinical prognostication.
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Imageamento por Ressonância Magnética , Tomografia Computadorizada Multidetectores , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Adulto , Algoritmos , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Fenótipo , Prognóstico , Radioterapia de Intensidade ModuladaRESUMO
Biological uncertainty remains one of the main sources of uncertainties in proton therapy, and is encapsulated in a scalar quantity known as relative biological effective (RBE). It is currently recognised that a constant RBE of 1.1 is not consistent with radiobiological experiment and may lead to sub-optimal exploitation of the benefits of proton therapy. To overcome this problem, several RBE models have been developed, and in most of these models, there is a dependence of RBE on dose-averaged linear energy transfer (LET), [Formula: see text]. In this work, we show that the [Formula: see text] estimation in these models during the data-fitting (or parameter estimation) phase could be subjected to a huge uncertainty due to not taking into account cellular materials during simulation, and this uncertainty can propagate down to the resulting RBE models. The dosimetric impact of this [Formula: see text] uncertainty is then evaluated on a simple clinical spread out Bragg peak (SOBP) and a prostate example. Our simulation shows that [Formula: see text] uncertainty due to the use of water as cellular material is non-negligible under low [Formula: see text] and low dose (2 Gy), and can be neglected otherwise. Thus, this study indicates that further dose and range margins may be required for low [Formula: see text] target under low dose. This is due to greater uncertainties in RBE model associated with incomplete knowledge of cellular composition for [Formula: see text] computation.
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Transferência Linear de Energia , Modelos Biológicos , Eficiência Biológica Relativa , Humanos , Terapia com Prótons , Radiometria , IncertezaRESUMO
Based on the ancient method of nine-steaming and nine-sun-curing,the chemical composition changes and quality profiles in different processes of Polygoni Multiflori Radix were studied. Their contents of stilbene glycoside,anthraquinones and polysaccharides were determined by nine-steaming and nine-sun-curing with black bean juice and pharmacopoeia method. HPLC chemical fingerprints were established,and orthogonal partial least squares-discriminant analysis( OPLS-DA) was performed on different processed products using SIMCA 14. 1 software to evaluate the quality difference between samples. The results of content determination show that,with the increase of the number of processing and steaming times,the stilbene glycoside and the combined anthraquinone showed a decreasing trend,and the free anthraquinone,total anthraquinone and polysaccharide showed an upward trend in the different preparations of Polygoni Multiflori Radix and Pharmacopoeia. Six-steamed and six-sun-cured products can be used as the finishing point for the classic steaming. Fingerprint results showed that there were significant differences in chemical composition in Polygoni Multiflori Radix at different processing processes. It can be identified stilbene glycoside( peak 13),emodin( peak 21),and physcion( peak 24). By comparing the relative peak areas of the 26 chromatographic peaks in the sample after normalization( the reference is peak 7),it was found that the relative peak areas of 12 peaks in the processed products were higher than the raw products,13 peaks were reduced; according to statistical analysis of OPLS-DA,Polygoni Multiflori Radix at different processing degrees was further divided into three categories,sample S1 was class I,S2-S5 were class Ⅱ,and S6-S11 were class Ⅲ. And 8 peaks with the VIP value higher than 1. 0 were peak 13,21,4,3,11,14,5,and 24 in order. The eight chemical components were the main components to distinguish the difference between Polygoni Multiflori Radix in the process of nine-steaming and nine-sun-curing,suggesting that it was rational to use stilbene glycoside,emodin and emodin methyl ether as quality control indicators of Polygoni Multiflori Radix. The method established in this experiment conformed to the methodological verification requirements,established a method of multi-component content determination combined with fingerprint,and clarified that six-steaming and six-sun-curing was used as an improved classical processing technology,and more clearly defined the whole dynamic change of chemical composition in Polygoni Multiflori Radix by nine-steaming and ninesun-curing process. It provides a basis for the chemical quality evaluation model about different processed products of Polygoni Multiflori Radix.
Assuntos
Antraquinonas/análise , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Medicamentos de Ervas Chinesas/química , Glicosídeos/análise , Análise dos Mínimos Quadrados , Compostos Fitoquímicos/análise , Raízes de Plantas/química , Polygonum/química , Polissacarídeos/análise , Vapor , Estilbenos/análise , Tecnologia Farmacêutica/métodosRESUMO
Objective: To evaluate the use of ITS2 sequences as DNA barcode to identify the Zingiberaceae medicinal plants from E'mei area. Method: The genomic DNAs were extracted from 43 Zingiberaceae medicinal plant samples from Sichuan E'mei area. The ITS2 sequences of these samples were amplified and bidirectionally sequenced by PCR. 40 ITS2 sequences were downloaded from the GenBank,and then the interspecific and intraspecific genetic distances were calculated and analyzed by using MEGA 6.0 to construct Neighbor-joining (NJ) tree; TAXON DNA software was also used to analyze intraspecific and interspecific variations and barcoding gaps. The differences in secondary structure of the ITS2 sequences were predicted and compared. Result: The minimum interspecific distance in Zingiberaceae samples was greater than the maximum intra specific distance,with obvious barcoding gap. The NJ tree showed that the samples were clustered into five different branches,Alpinia,Curcuma,Globba,Hedychium,and Zingiber respectively,and further cluster into sub-branches. Significant differences were also present in the secondary structures of ITS2 between different samples. Conclusion: ITS2 sequences as DNA barcode can be used to conduct accurate and rapid identification of the Zingiberaceae plants and clearly figure out the phylogenetic relationship among them,providing guidance for the study of the distribution of medicinal plants of this genus,as well as theoretical basis for the quality control,medication safety and rational development of Zingiberaceae medicinal plants in E'mei area.