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Brain edema belongs to the category of "stroke" and "true headache", while Traditional Chinese Medicine mostly understands its core disease mechanisms from the perspectives of stasis, deficiency, and heat, and mostly treats the disease by using warming yang to induce diuresis and eliminating stasis to remove water. Wuling Powder has been lauded as the "first party to typhoid and relieving diuresis", which is used to cure clearing damp and promoting diuresis and warming yang and transforming qi, and has been clinically used in the treatment of brain edema caused by various causes such as head trauma, intracerebral hemorrhage, cerebral infarction, and intracranial space occupying, all with remarkable efficacy. Wuling Powder improves cellular energy supply, scavenges excess oxygen radicals and calcium ions in brain tissue, and reduces the damage to brain tissue caused by vascular inflammatory factors and regulates aquaporins and vascular endothelial growth factor, thereby achieving therapeutic effects.
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Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD's ACE inhibitory ac-tivities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to un-cover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.
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Objective:To explore the application value of heparin-binding protein (HBP) in the early diagnosis and assessment of severe adenovirus pneumonia.Methods:A total of 90 children diagnosed with adenovirus pneumonia admitted in the Department 1 of Emergency and Pediatric Intensive Care Unit 1 in Hunan Children′s Hospital from January 2019 to March 2020 were recruited.HBP levels in children with adenovirus pneumonia were detected.The correlation between HBP with white blood cell count (WBC), neutrophil ratio (N), C-reactive protein (CRP), interleukin-6(IL-6) and erythrocyte sedimentation rate (ESR) were examined.Receiver operating characteristic(ROC) curve analysis was conducted to explore the value of HBP in the early diagnosis and assessment of severe adenovirus pneumonia.Children with adenovirus pneumonia were divided into severe adenovirus pneumonia group (severe group) and non-severe adenovirus pneumonia group (non-severe group) according to their severity.Those in the severe group were further divided into bronchiolitis obliterans(BO) group and non-BO group according to the occurrence of BO.Results:(1) The HBP level in children with adenovirus pneumonia was (49.47±34.19) μg/L, which was significantly higher in the severe group than that of non-severe group[(82.88±44.02) μg/L vs.(35.15±13.08) μg/L, t=15.349, P<0.05]. Children in the severe group were significantly younger, and they had a significantly longer length of stay, lower Pediatric Critical Illness Scores (PCIS), and higher inflammatory markers like HBP, WBC, N, CRP, IL-6, and ESR compared with those of the non-severe group (all P<0.05). No significant difference in the procalcitonin (PCT) level was detected between groups.(2) The HBP was positively correlated with inflammatory markers like WBC ( r=0.38, P<0.05), N ( r=0.26, P<0.05), CRP ( r=0.47, P<0.05), IL-6 ( r=0.76, P<0.05), and ESR ( r=0.35, P<0.05). However, HBP did not have a significant correlation with PCT ( r=0.097, P>0.05). (3) In the severe group, the HBP level of the children with invasive mechanical ventilation, oxygenation index(P/F index)≤ 200 mmHg (1 mmHg=0.133 kPa) and BO was significantly higher than that of the non-invasive mechanical ventilation, P/F index> 200 mmHg and non-BO (all P<0.05). (4) The area under the ROC curve of HBP, WBC, N, CRP, ESR and IL-6 in predicting the severity of adenovirus pneumonia were 0.915, 0.748, 0.770, 0.740, 0.820 and 0.798, respectively.When the cut-off value of HBP was 45 μg/L, the sensitivity and specificity of HBP were 81.48% and 85.71%, respectively. Conclusions:As an inflammatory mediator, HBP is involved in the inflammatory response of the body.It may be a useful new marker for the early diagnosis of severe adenovirus infection, which also has a certain value in the evaluation of the severity and prognosis of the disease.The findings provide a basis for early clinical intervention and treatment of adenovirus infection in children.
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Objective:To investigate whether miRNA-296-5p can inhibit enterovirus 71 (EV71) virus replication in neural cells SK-N-SH by targeting the phosphatase and tensin homology deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinases (AKT) signaling pathway.Methods:Serum samples were collected from patients with EV71 virus-infected hand-foot-mouth disease and normal physical examination, and the expressions of serum inflammatory factors procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) , interleukin-6 (IL-6), IL-1β, and IL-13 were detected by enzymelinked immunosorbent assay (ELISA). Human neuroblastoma SK-N-SH cells infected by EV71 virus in logarithmic growth phase were set up as control group, miRNA-296-5p mimic group and miRNA-296-5p inhibitor group. The transfection was carried out according to the Lipofectamine 2000tm cell transfection reagent. The expression of EV71-VP1 gene mRNA and protein and PTEN/PI3K/Akt signal pathway related molecules in three groups of cells was observed by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blot.Results:ELISA test results showed that the levels of serum inflammatory factors PCT, CRP, TNF-α, IL-1β, IL-6 and IL-13 in patients with EV71 virus-infected hand, foot and mouth disease were significantly higher than those in normal physical examination ( P<0.05). The results of qRT-PCR and Western blot showed that the mRNA and protein levels of mirna-296-5p and PTEN in SK-N-SH were significantly decreased after EV71 virus infection, while the mRNA and protein levels of EV71-VP1 and molecules related to PI3K/AKT signaling pathway were significantly increased ( P<0.05). The expression of PTEN was significantly increased in the miRNA-296-5p mimic group, and the expression of EV71-VP1 and the activation of the PI3K/AKT signaling pathway were inhibited, while the effect was reversed in the miRNA-296-5p inhibitor group ( P<0.05). Conclusions:MiRNA-296-5p inhibits the replication of EV71 virus in neural cells SK-N-SH by targeting the PTEN/PI3K/AKT signaling pathway, while reducing the cellular inflammatory response, targeting miRNA-296-5p and downstream PTEN/PI3K/AKT The signal pathway is expected to provide therapeutic targets and theoretical basis for the treatment of hand-foot-mouth disease caused by clinical EV71 virus.
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Platelets,which are derived from the multifunctional hematopoietic stem cells in the hematopoietic system of bone marrow,are small pieces of cytoplasm which was partially exfoliated from the bone marrow megakaryotic cells,and play an important role in the physiological hemostasis and coagulation process.Tumor cells transfer biomolecules (such as RNA) to platelets by direct contact or exosomes release,resulting in changes in platelet precursor RNA.Through the effect of tumor cells and microenvironment,precursor RNA of platelet is spliced to mature RNA and then transformed into functional protein to responds to external stimulation,which is forming tumor-educated platelets.The detection of tumor-educated platelets of peripheral blood of patients is expected to be used in clinical tumor diagnosis.The novel liquid biopsy method can be a replacement or supplement for current tumor detection methods.Further study of the role of tumor-educated platelets in the diagnosis of tumors will provide a new theoretical basis for clinical diagnosis of tumors.
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OBJECTIVE@#To investigate the effect of Shenmai injection on myocardial cells with oxidative injury and the underlying mechanisms.@*METHODS@#Tert-butyl hydroperoxide (t-BHP) was used to induce the oxidative stress in H9c2 myocardial cells. The cell viability and ATP level were evaluated using MTT-colorimetric method and CellTiter-Glo luminescent cell viability assay. The oxygen respiration rate was examined by Clark oxygen electrode. Pyruvate and pyruvate dehydrogenase (PDH) levels were evaluated by ELISA kit. Western blot and quantitative real-time RT-PCR were employed to evaluate the expression of pyruvate dehydrogenase alpha 1(PDHA1) and pyruvate dehydrogenase kinase 1(PDK1).@*RESULTS@#Shenmai injection significantly improved viability and respiration of H9c2 myocardial cells after t-BHP injury (0.05).@*CONCLUSIONS@#Shenmai injection protects mitochondria from oxidative stress by increasing PDH level, which indicates that it may improve energy metabolism of myocardial cells.
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Animals , Rats , Cell Line , Cell Survival , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Gene Expression Regulation , Mitochondria , Myocytes, Cardiac , Oxidative Stress , Protein Serine-Threonine Kinases , Genetics , Pyruvate Dehydrogenase (Lipoamide) , GeneticsABSTRACT
Protein arginine methyltransferase (PRMT) can methylate a variety of proteins,including histones and non-histones,affecting a variety of cellular processes such as transcription,RNA splicing,DNA repair,and cell cycle control.The activity of PRMT is affected by a variety of regulatory mechanisms,and its abnormal expression plays an important role in the development of the diseases,especially in tumors such as breast cancer and leukemia.PRMT has a unique value in the diagnosis or treatment of tumors.With the further exploration of PRMT methylation mechanism,PRMT selective inhibitors have made some progress.PRMT-specific inhibitors are expected to be targeted drugs for the treatment of tumors.
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To discover the nephroprotective substances from Huangkui capsule.The components of Huangkui capsule were isolated by preparative liquid chromatography, and the active components were screened by LC/MS and identified. The adriamycine-injured HK-2 cells were treated with various active components with different concentrations, and the malonaldehyde (MDA) content, adenosine triphosphate (ATP) level and mitochondrial oxygen consumption rate were measured to verify the protective activity of the compounds.Four active components in Huangkui capsule were identified to exert nephroprotective effects. Fifteen flavanoids from these four components were tentatively identified by LC/MS, and hyperin, myricetin, quercetin, rutin and isoquercetin were confirmed. Hyperin, myricetin quercetin and rutin showed dose-dependent protective effects on injured HK-2 cells. Espacially, hyperin significantly reduced MDA content, quercetin and rutin significantly increased ATP level, and myricetin significantly increased mitochondrial oxygen consumption rate.Hyperin, myricetin, querctein and rutin might be the potential nephroprotective compounds in Huangkui capsule, their effects may be related to the inhibition of lipid peroxidation and the alleviation of mitochondrial damage.
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Abelmoschus , Chemistry , Adenosine Triphosphate , Metabolism , Cell Line, Transformed , Chromatography, Liquid , Doxorubicin , Drugs, Chinese Herbal , Epithelial Cells , Flavonoids , Pharmacology , Kidney Diseases , Drug Therapy , Kidney Tubules, Proximal , Lipid Peroxidation , Malondialdehyde , Metabolism , Mass Spectrometry , Mitochondria , Oxygen Consumption , Protective Agents , Chemistry , Pharmacology , Quercetin , Pharmacology , Rutin , PharmacologyABSTRACT
Quality control of traditional Chinese medicine is of great importance to ensure its safety and effectiveness in clinic,and is also an obstacle impeding the modernization of traditional Chinese medicine.Though,the complexity of traditional Chinese medicine resulted in some relative weakness of quality standard researches.The critical point need addressing is to establish a sound quality standard system conforming to the characteristics of traditional Chinese medicine in the process of the modernization of Chinese medicine.In this paper,in regard to Dan Hong injection,discriminant strategy of Q-Markers from traditional Chinese medicine injection was clarified from three aspects:what ingredients,which to control and how to control,providing a new vision in the field of the quality standard researches of traditional Chinese medicine.
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Recently,increasing cancer researches focus on antibody-drug conjugates(ADCs) which can improve the anti-tumor potency with less adverse effect while benefiting patients in the future. However,safety evaluation of ADCs is a big challenge because of complex components as well as in experience in preclinical studies. In this review,the authors reviewed the mode of action,hazard risks,and toxicity observed in preclinical/clinical studies of ADCs,summarized the preclinical studies of Adcetris(brentuximab vedotin)and Kadcyla(ado-trastuzumab emtansine),and suggested a better strategy of ADCs in preclinical safety evaluation.
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Objective To investigate myostatin gene mRNA expression in the muscle tissue from patients with muscle weakness suffering from different illness.Methods The clinical data of our patients were all from the Muscular Disease Center,Department of Neurology,People' s Liberation Army General Hospital.A total of 75 patients suffered from muscular weakness were included consecutively.Skeletal muscle biopsies were obtained with informed consent from all 75 patients.The diagnosis was confirmed by two senior doctors for muscular disease according to the clinical feature,the results of electromyography,serum creatine kinase activity and histopathological examination.Among of them,21 cases were diagnosed as polymyositis,15 cases progressive muscular dystrophy,5 cases neurogenic amyotrophy,4 cases chronic muscle fiber damage,4 cases mitochondrial myopathy,4 cases lipid storage myopathy,4 cases myotonic dystrophy,3 cases muscular dystrophy in adults,2 cases dermatomyositis,and 2 cases inclusion body myositis.There were 2 cases characterized by pure high activity of creatine kinase.And the other 9 cases were diagnosed as non-neuromuscular disease.The expression of myostatin gene mRNA in muscle tissue was evaluated by reverse transcription polymerase chain reaction method,with glyceraldehyde-3-phosphate dehydrogenase as internal reference.Results The expression of myostatin gene mRNA was detected in 63 patients,but not in other 12 cases,and the percentage of positive expression was 84％.The expression index was with great variation,from 0 to 3.52.In positive cohort,the index was correlated positively with the duration of disease (r =0.236,P =0.041).The activities of creatine kinase in positive expression cohort were higher than that of negative one,but nonsignificantly.Conclusion The expression of myostatin gene mRNA in muscle tissue may not correlate to the entity of atrophic muscular disease because of its great variation.
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<p><b>OBJECTIVE</b>To establish a new rapid method to screen potential hepatoprotective compounds from traditional Chinese medicine, and identify the hepatoprotective compounds in Paeoniae Radix Rubra.</p><p><b>METHOD</b>Fluorescein diacetate labelled and MTT assay were applied for screening the hepatoprotective fractions on HepG2 cells exposed to galactosamine. The active fractions were analyzed by chromatography coupled with mass spectrometry. Finally, the hepatoprotective effects of the identified compounds were validated by hepatoprotective assay.</p><p><b>RESULT</b>Three hepatoprotective fractions were founded, in which three compounds were identified as paeoniflorin, ethyl palmitate and ethyl linoleate. Validation results indicated that all the three compounds can attenuate the galactosamine induced injury on HepG2 cells.</p><p><b>CONCLUSION</b>Paeoniflorin, ethyl palmitate and ethyl linoleate from paeoniae radix rubra showed potential hepatoprotective activity.</p>
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Humans , Benzoates , Pharmacology , Bridged-Ring Compounds , Pharmacology , Glucosides , Pharmacology , Hep G2 Cells , Linoleic Acids , Pharmacology , Liver , Monoterpenes , Paeonia , Chemistry , Palmitic Acids , Pharmacology , Protective AgentsABSTRACT
<p><b>OBJECTIVE</b>To sift and identify the nephrotoxic components in Zexie for controlling the quality of the herb.</p><p><b>METHOD</b>The fractions of zexie were prepared by Pre-HPLC, then the nephrotoxicity of the fraction was sifted using LLC-PK1 labelled with fluorescein diacetate and MTT assay. Finally, the compounds in the most obvious nephrotoxic fraction were identified with LC-MS.</p><p><b>RESULT</b>Using MTT and FDA assay, similar results were obtained. Fraction C13 was found to be the most toxic with FDA assay, in which three compounds, alisol C, 16, 23-oxido-alisol B and alisol O, were detected and characterized by multi -stage mass spectrometric analysis.</p><p><b>CONCLUSION</b>Alisol C, 16, 23-oxido-alisol B and alisol O in Zexie may cause nephrotoxicity.</p>
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Animals , Alisma , Chemistry , Toxicity , Chromatography, High Pressure Liquid , Kidney , LLC-PK1 Cells , Mass Spectrometry , SwineABSTRACT
The concept and framework of network toxicology and network toxicology of traditional Chinese medicine has been proposed in this paper. The related tools and technologies have been briefly introduced, and the prospects for network toxicology of traditional Chinese medicine are forecasted.
Subject(s)
Animals , Humans , Drug Interactions , Drugs, Chinese Herbal , Toxicity , Medicine, Chinese TraditionalABSTRACT
Objective To explore the expression of myostatin mRNA,a negative regulator of muscle growth,in the skeletal muscle of Duchenne muscular dystrophy(DMD)patients.Methods A semi-quantitative reverse transcription polymerase chain reaction was performed to evaluate the expression of myostatin in the skeletal muscle of 7 DMD patients and 4 healthy controls.Results The level of myostatin gene expression in the skeletal muscle of DMD patients was higher than that of healthy controls(0.56 ± 0.16 vs 0.34 ± 0.15,Z =-2.268,P =0.023).Conclusions The myostatin gene expression was increased in the DMD patients compared to the healthy controls.Enhanced expression of myostatin in the skeletal muscle might be involved in the pathogenesis of DMD.
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In the present study, A fluorescent imaging-based high-throughput screening method was developed for identifying anti-migratory compounds with 96-well Transwell plates. The correlation, precision and stability of this method were examined and the incubation time of dye Hoechst 33342 in addition to migration time was optimized. In addition, The inhibitory activity of anti-cancer drug paclitaxel on tumor cell migration was assayed and an IC50 value of 0.717 micromol x L(-1) was obtained. Using this method, 24 components from Rhizoma Alismatis were screened and one component with anti-migration activity was found. These results show that the new proposed method with good precision, stability and linear range has the potential to assay the inhibitory activity of anticancer compounds.
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Objective This study investigated the differences between axillary temperature monitored for 5min and 10min with mercury in glass thermometers. Methods A sample of 365 patients had axillary temperatures monitored for five minutes and ten minutes, Relevant research data were analyzed by meta analysis. Results At α=0.05 level, the result of paired t test between 5 minutes and 10 minutes temperature indicated that there was statistical difference, Meta analysis had the same result, Temperaturedata of 365 patients were expressed in the Bland-Altman plot which displayed that their consistency can not be accepted in the professional. Conclusions The optimal axillary mercury thermometer placement time for recording human body temperature is 10 minutes.
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Objective To observe the changes of carotid intima-media thickness(CIMT) and vascular endothelia function in patients with geriatric carotid plaque before and after intensive lipid lowering was performed.Methods 102 patients diagnosed with carotid plaque were ramdomly divided into common group (atorvastatin 10 mg/d,n=48) and intensive lipid lowering group (atorvastatin 20 mg/d,n=54).After one year of treatment,the fasting venous blood total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),high density lipeprotein cholesterol (HDL-C) and triglyceride (TG) were assayed,and the thickest and thinnest CIMT and brachial arterial.endothelium dependent diastolic function (FMD) and carotid artery plaque index(PI) were measured by ultrasound.Results Two groups in the thickest CIMT and PI had no significant difference before and after treatment (P＞0.05).The levels of FMD,TC,LDL-C,TG and the thinnest CIMT had significant difference before and after therapy [common group:GIMT(0.85±0.20)mm,(0.83±0.22) mm,FMD(3.85±1.41)%,(7.91±1.05)%,TC(6.46±1.05) mmol/L,(4.82±1.26) mmol/L,LDL-C (4.71±1.00) mmol/L,(3.16±1.00) mmol/L,TG (1.55±0.45) mmol/L,(1.49±0.44) mmol/L;intensive lipid lowering group:CIMT(0.84±0.20) mm,(0.63±0.17) mm,FMD (3.74±1.38) %,(0.25±1.58)%,TC (6.36±1.06) mmol/L,(4.10±1.00) mmol/L,LDL-C (4.73±1.01) mmol/L、(2.28±1.26) mmol/L,TG (1.56±0.53) mmol/L,(1.50±0.49) mmol/L,P＜0.05].After one year's therapy,the difference in intensive lipid lowering group was more obvious than in common group (P＜0.05).Conclusions Intensive lipid lowering therapy is more effective to decrease TC,LDL-C and CIMT and to improve the vascular endothelia function.Atorvastatin is effective to stabilize the plaque and to retard the atheroscleresis development.
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Objective To explore the demands of nursing staff on nursing repository and provide reference for the develop-ment of nursing repository. Methods In-depth interview was conducted on 21 nursing staff by qualitative research. The themes were formed by category analysis. Results There were four themes about the demands of nursing staff on nursing repository:necessity to develop nursing repository ,contents of the repository ,forms of the repository and prospect of the reposi-tory. Conclusions Nursing staff need a nursing repository. They hope that the repository can provide comprehensive,concrete and practical knowledge,and provide a good interface with digitization. The design of repository should be consistent with in-ternational standards.
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Objective The incidence rate of complication during central venous catheterization through internal jugular vein (IJV) and subclavian vein (SV) puncture. Methods Clinical controlled trials about IJV and SV puncture were collected and related literatures were screened according to the criteria of inclusion. The literatures underwent Meta analysis and subsequent analysis of sensitivity. Results A total of 18 literatures were included. Meta analysis indicated that statistical difference existed in the related infection rate [RR=1.74, 95%CI (1.32, 2.30)] and arterial puncture [RR=3.19, 95%CI (1.70, 5.99)], but not in the one-time-puncture success rate [RR=1.06, 95%CI (0.90, 1.24)] between IJV and SV puncture. Conclusions The rate of related infection and arterial puncture was higher by IJV than by SV puncture. But we could not confirm if any difference existed in the one-time-puncture success rate between the two methods. The results still needs evaluation by high-quality randomly controlled experiments.