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Occupational exposure to diacetyl can lead to bronchiolitis obliterans. In this paper, two patients with severe obstructive ventilation disorder who were exposed to diacetyl at a fragrance and flavours factory were analyzed. The clinical manifestations were cough and shortness of breath. One of them showed Mosaic shadows and uneven perfusion in both lungs on CT, while the other was normal. Field investigation found that 4 of the 8 workers in the factory were found to have obstructive ventilation disorder, and 2 had small airway dysfunction. This paper summarizes the diagnostic process of patients in order to improve the understanding of airway dysfunction caused by occupational exposure to diacetyl and promote the development of relevant standards.
Subject(s)
Humans , Diacetyl/adverse effects , Occupational Diseases/diagnosis , Occupational Exposure/adverse effects , Lung , Bronchiolitis Obliterans/diagnosisABSTRACT
Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio<sup>®</sup> cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （<italic>P</italic><0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of <italic>γ-</italic>interferon （IFN-<italic>γ）</italic>， interleukin-10 （IL-10）， IL-4， and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group （<italic>P</italic><0.05）， which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.
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Objective:To analyze active components， its targets and signaling pathways of Shenlian formula based on network pharmacology， and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease （ASCVD）， in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine （TCMSP）， its target proteins were obtained by SymMap and ETCM Databases， and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions （PPI） network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds， 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 （PTGS2）， estrogen receptor 1 （ESR1） and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic， nitric oxide biosynthetic process， response to estradiol， angiogenesis， inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway， phosphatidylinositol-3 kinase （PI3K）/ protein kinase B （Akt） signaling pathway， hypoxia induction factor-1 （HIF-1） signaling pathway and apoptosis. Among them， the regulatory effect of Shenlian formula on apoptosis may act on not only TP53， but also different signaling pathways of apoptosis respectively， thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area， improve the myocardial histopathological changes， and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD， and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.
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Cerebral malaria (CM) is the deadliest complication of Plasmodium falciparum infection and even with effective anti-malarial treatment the mortality of children can be as high as 18%; up to one-third of CM survivors are left with neurological and cognitive deficits. The pathophysiology of CM is not completely understood, but mechanical obstruction and immunopathology are its mainstream theories. Adjuvant therapy aims to improve clinical outcomes and/or reduce mortality, as well as preventing long-term neurocognitive deficits. Improving survival and reducing neurological damage to survivors are new goals for new antimalarials and adjuvant therapies. Herein, we discussed what is known about the disease mechanism of CM and systematically summarize the progress of adjuvant therapy research in protecting the vascular endothelium, reducing adhesion formation, regulating immune balance, interfering with malarial metabolism, protecting nerves, improving nitric oxide bioavailability, improving energy metabolism and alleviating inflammation, with the aim of exploiting this understanding to reduce the neurological damage to children with CM. This work also highlights some preclinical studies which may be candidate strategies in future clinical trials.
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Plasmodium culture in vitro is often used as an antimalarial drug evaluation model, but the lifecycle of P. falciparum culture in vitro tends to be disordered, which affects the research and evaluation of antimalarial drug mechanism in vitro. By combining magnetic bead separation method with sorbitol synchronization method, a synchronization method was constructed to quickly acquire different lifecycles of P. falciparum and obtain large amounts of parasite with a narrow synchronization window in a short period. Furthermore, the dihydroartemisinin(DHA) was used to treat the early trophozoite phase of P. falciparum 3 D7 for 4 h. Then mRNA was extracted and RNA-seq was conducted to analyze the differential expression of mRNA after drug treatment and obtain the differential gene expression profile. Differential expression of up-regulated genes and down-regulated genes was analyzed according to the screening criteria of |log_2FC|>1 and P<0.05. There, 262 genes were up-regulated and 77 genes were down-regulated. GO functional enrichment analysis of all the differentially expressed genes showed that the enrichment items mainly included cell membrane components, transporter activity, serine/threonine kinase activity, Maurer's clefts(MCs), rhoptry, antigen variation and immune evasion. The enrichment of KEGG pathway included malaria, fatty acid metabolism and peroxisome. Protein-protein interaction(PPI) analysis showed that the down-regulated genes in the modules with high degree of association included rhoptry, myosin complex, transporter and other genes related to the important life activities of malaria invasion and immune escape; the up-regulated genes were mainly related to various toxic exportins of malaria, such as PfSBP1 of MCs. qRT-PCR was used to verify the expression level of some genes, and most of the results were the same as the sequencing results. SBP1 was significantly up-regulated, while some antigenic protein expression levels were down-regulated. Above all, key molecules of DHA therapy were mainly involved in the parasites' rhoptry, transporter, antigenic variation, plasmodium exportin. These results offer us many hints to guide the further studies on mechanism of artemisinin and provide a new way for development of new antimalarial drugs.
Subject(s)
Animals , Antimalarials , Artemisinins , Erythrocytes , Plasmodium falciparum , TranscriptomeABSTRACT
Corona virus disease 2019(COVID-19) has brought untold human sufferings and economic tragedy worldwide. It causes acute myocardial injury and chronic damage of cardiovascular system, which has attracted much attention from researchers. For the immediate strategy for COVID-19, "drug repurposing" is a new opportunity for developing drugs to fight COVID-19. Artemisinin and its derivatives have a wide range of pharmacological activities. Recent studies have shown that artemisinin has clear cardiovascular protective effects. This paper summarizes the research progress on the pathogenesis the pathogenesis of COVID-19 in cardiovascular damage by 2019 novel coronavirus(2019-nCoV) virus from myocardial cell injury directly by 2019-nCoV virus,viral ligands competitively bind to ACE2 and then reduce the protective effect of ACE2 on cardiovascular disease, "cytokine storm" related myocardial damage, arrhythmia and sudden cardiac death induced by the infection and stress, myocardial injury by hypoxemia, heart damage side effects from COVID-19 drugs and summarizing the cardiovascular protective effects of artemisinin and its derivatives have activities of anti-arrhythmia, anti-myocardial ischemia, anti-atherosclerosis and plaque stabilization. Then analyzed the possible multi-pathway intervention effects of artemisinin-based drugs on multiple complications of COVID-19 based on its specific immunomodulatory effects, protective effects of tissue and organ damage and broad-spectrum antiviral effect, to provide clues for the treatment of cardiovascular complications of COVID-19, and give a new basis for the therapy of COVID-19 through "drug repurposing".
Subject(s)
Humans , Artemisinins , COVID-19 , Cardiovascular Diseases , Heart Diseases , SARS-CoV-2ABSTRACT
Objective:By means of network pharmacology, the active ingredients, targets and molecular pathways of Shengmaiyin (Dangshen prescription) in the treatment of atherosclerotic cardiovascular disease (ASCVD) were studied, in order to reveal the molecular mechanism of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD, and provide the rational explanation of the compatibility of the combination. Method:The main chemical components of Shengmaiyin (Dangshen prescription) were obtained by means of SymMap database, traditional Chinese medicine systems pharmacology database and analysis platform（TCMSP）platform and BATMAN-TCM platform. Compound targets were retrieved by SymMap and the Encyclopedia of Traditional Chinese Medicine （ETCM）, and disease targets were retrieved by DisGeNET and GeneCards databases. The intersections of compound targets and disease targets were used to obtain the predicted targets of song-decoction on ASCVD. The Protein-Protein Interaction (PPI) network diagram was constructed through STRING database, and key compounds and targets of Shengmaiyin (Dangshen prescription) acting on ASCVD were obtained through Cytoscape. Finally, the enriched key targets were put for Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis through the Database for Annotation，Visualization and Integrated Discovery（DAVID）. Result:There were 33 key compounds and 25 key targets of Shengmaiyin (Dangshen prescription) for ASCVD. The GO analysis showed that the biological functions of Shengmaiyin (Dangshen prescription) in the treatment of key ASCVD targets mainly involved biological processes, such as the regulation of apoptosis, inflammatory response, regulation of nitric oxide synthesis and regulation of insulin secretion. The KEGG pathway was mainly enriched in 20 signaling pathways, including tumor necrosis factor(TNF) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, apoptosis signaling pathway and estrogen signaling pathway. Conclusion:Through network pharmacology, this study explored active ingredients and potential targets of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD at the molecular level, preliminarily verified the mechanism of action of Shengmaiyin (Dangshen prescription), and laid a theoretical foundation for further study on the mechanism of action.
ABSTRACT
In ischemic stroke, increased level of neuronal complex of nitric oxide synthase (nNOS)-postsynaptic density protein-95 (PSD-95) plays an important role in neuronal damage. We aimed to establish a screening model to identify compounds capable of uncoupling nNOS interaction with PSD-95. In this model, human embryonic kidney-293T (HEK-293T) cells were transfected with either pCDH-Flag-nNOS or pcDNA3.1-PSD-95 plasmid to obtain the protein of Flag-nNOS or PSD-95. Incubating Flag-nNOS with PSD-95 causes formation of the nNOS-PSD-95 complex. ZL006, a known uncoupler of nNOS-PSD-95 interaction, can disturb the interaction between Flag-nNOS and PSD-95, serving as a positive control. The method coupling antibodies to magnetic beads with glutaraldehyde was used to decrease the cost and increase the efficiency. To establish that our model is suitable for selecting nNOS-PSD-95 uncouplers, we evaluated the ability of IC87201, another reported uncoupler of nNOS-PSD-95 interaction, and structural analogs of ZL006. IC87201 and one structure analog of ZL006 showed uncoupling effect, supporting that our model can be used to select different types uncoupler blocking nNOS-PSD-95 interaction.
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Background@#Sleep disorders are one of the earliest non-motor symptoms of Parkinson’s disease (PD). Sleep disorders could, therefore, have value for recognition and diagnosis in PD. However, no unified classification and diagnostic criteria exist to evaluate sleep disorders by polysomnography (PSG). Utilizing PSG to monitor sleep processes of patients with PD and analyze sleep disorder characteristics and their relationship with demographic parameters could aid in bridging this gap. This preliminary study aimed to evaluate the clinical characteristic of sleep disorders in PD using PSG.@*Methods@#PSG was used to evaluate sleep disorders in 27 patients with PD and 20 healthy volunteers between August 2015 and July 2018 in Fujian Medical University Union Hospital. Total sleep time (TST), sleep efficiency (SE), total wake time, and other parameters were compared between the two groups. Finally, the correlation between sleep disorders and age, disease duration, Unified Parkinson’s Disease Rating Scale-III scores, Hoehn-Yahr stage, and levodopa dose were analyzed. The main statistical methods included Chi-square test, two independent samples t test, Fisher exact test, and Pearson correlation.@*Results@#Sleep fragmentation in the PD group was significantly increased (74.1%) while difficulty falling asleep and early awakening were not, as compared to healthy controls. No significant differences were found in time in bed, sleep latency (SL), non-rapid eye movement (NREM) stage 1 (N1), N1%, N2, N2%, N3%, and NREM% between PD and control groups; but TST (327.96 ± 105.26 min vs. 414.67 ± 78.31 min, P = 0.003), SE (63.26% ± 14.83% vs. 76.8% ± 11.57%, P = 0.001), R N3 (20.00 [39.00] min vs. 61.50 [48.87] min, P = 0.001), NREM (262.59 ± 91.20 min vs. 337.17 ± 63.47 min, P = 0.003), rapid-eyemovement (REM) (32.50 [33.00] min vs. 85.25 [32.12] min, P < 0.001), REM% (9.56 ± 6.01 vs. 15.50 ± 4.81, P = 0.001), REM sleep latency (157.89 ± 99.04 min vs. 103.47 ± 71.70 min, P = 0.034) were significantly reduced in PD group.@*Conclusion@#This preliminary study supported that sleep fragmentation was an important clinical characteristic of sleep disorders in PD. Whether sleep fragmentation is a potential quantifiable marker in PD needs to be further investigated in the future study.
ABSTRACT
BACKGROUND@#Sleep disorders are one of the earliest non-motor symptoms of Parkinson's disease (PD). Sleep disorders could, therefore, have value for recognition and diagnosis in PD. However, no unified classification and diagnostic criteria exist to evaluate sleep disorders by polysomnography (PSG). Utilizing PSG to monitor sleep processes of patients with PD and analyze sleep disorder characteristics and their relationship with demographic parameters could aid in bridging this gap. This preliminary study aimed to evaluate the clinical characteristic of sleep disorders in PD using PSG.@*METHODS@#PSG was used to evaluate sleep disorders in 27 patients with PD and 20 healthy volunteers between August 2015 and July 2018 in Fujian Medical University Union Hospital. Total sleep time (TST), sleep efficiency (SE), total wake time, and other parameters were compared between the two groups. Finally, the correlation between sleep disorders and age, disease duration, Unified Parkinson's Disease Rating Scale-III scores, Hoehn-Yahr stage, and levodopa dose were analyzed. The main statistical methods included Chi-square test, two independent samples t test, Fisher exact test, and Pearson correlation.@*RESULTS@#Sleep fragmentation in the PD group was significantly increased (74.1%) while difficulty falling asleep and early awakening were not, as compared to healthy controls. No significant differences were found in time in bed, sleep latency (SL), non-rapid eye movement (NREM) stage 1 (N1), N1%, N2, N2%, N3%, and NREM% between PD and control groups; but TST (327.96 ± 105.26 min vs. 414.67 ± 78.31 min, P = 0.003), SE (63.26% ± 14.83% vs. 76.8% ± 11.57%, P = 0.001), R N3 (20.00 [39.00] min vs. 61.50 [48.87] min, P = 0.001), NREM (262.59 ± 91.20 min vs. 337.17 ± 63.47 min, P = 0.003), rapid-eye-movement (REM) (32.50 [33.00] min vs. 85.25 [32.12] min, P < 0.001), REM% (9.56 ± 6.01 vs. 15.50 ± 4.81, P = 0.001), REM sleep latency (157.89 ± 99.04 min vs. 103.47 ± 71.70 min, P = 0.034) were significantly reduced in PD group.@*CONCLUSION@#This preliminary study supported that sleep fragmentation was an important clinical characteristic of sleep disorders in PD. Whether sleep fragmentation is a potential quantifiable marker in PD needs to be further investigated in the future study.
ABSTRACT
Polycystic ovary syndrome(PCOS)is one ofthe most common endocrine disorders in women,whichis associated with metabolic abnormalities and long-term complications including diabetes and cardiovas-cular diseases.When diagnosed with PCOS,patientsneed to undergo screening tests on glycolipid metab-olism in time,in order to conduct early intervention toreduce the cardiovascular and diabetic risk.Manage-ments of glycolipid metabolic disorders in PCOS shouldbe based on the characteristics of different phenotypesand patients' needs in order to perform individualtreatments.
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Magnetic molecularly imprinted polymers(MMIPs) were prepared with ZL006 as template, acrylamide(AA) as the functional monomer, and acetonitrile as pore-forming agent; then Fourier transform infrared spectroscopy(FT-IR) and scanning electron microscopy(SEM) were used to characterize their forms and structures. Simultaneously, the MMIPs prepared previously were used as sorbents for dispersive magnetic solid phase extraction(DSPE) to capture and identify potential nNOS-PSD-95 uncouplers from extracts of Trifolium pratense and the the activities of the screened compounds were evaluated by the neuroprotective effect and co-immunoprecipitation test. The experiment revealed that the successfully synthesized MMIPs showed good dispersiveness, suitable particle size and good adsorption properties. Formononetin, prunetin and biochanin A were separated and enriched from Trifolium pratense by using the MMIPs as artificial antibodies and finally biochanin A was found to have higher cytoprotective action and uncoupling action according to the neuroprotective effect and co-immunoprecipitation test.
Subject(s)
Adsorption , Genistein , Chemistry , Molecular Imprinting , Phytochemicals , Chemistry , Polymers , Chemistry , Solid Phase Extraction , Spectroscopy, Fourier Transform Infrared , Trifolium , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes.</p><p><b>METHODS</b>C57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined.</p><p><b>RESULTS</b>Compared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue.</p><p><b>CONCLUSION</b>Nicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by increasing GIP and GLP-1 contents in the hippocampus and promoting antioxidation to relieve hippocampal injury.</p>
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Malaria is still the most severe strain of the human malaria parasites, and malaria disease is life-threatening which can result in severe anemia and cerebral malaria, especially in children in tropical Africa. Previous studies have shown that artemisinin and its derivatives could selectively kill erythrocytic stage of malaria and have a greater impact on the ring period. In recent years, there have been new findings of its mechanism continually. However, the concentration of artemisinin and its derivatives used in these studies can reach 50 to 80 times the half-inhibitory concentration in vitro. In this study, the international standard strain 3D7 of Plasmodium falciparum was used to culture in vitro. After half-inhibitory concentration of dihydroartemisinin was treated, the morphological changes of P. falciparum intraerythrocytic stage were observed, and then the 3D7 life cycle and effects of different developmental stages after dosing was explored. The 3D7 strain of P. falciparum was continuously synchronised more than 3 times. And dihydroartemisinin (DHA) at half maximal inhibitory concentration (10 nmol·L⁻¹) was administered for 6 hours after the last synchronization, and 3 life cycles were continuously observed (132 h). The results showed that compared with the parasites untreated by DHA, there was a noticeable delay in the life cycle of at least 36 h, indicating that the growth of 3D7 was significantly inhibited by DHA (<0.001), and the rate of ring formation was significantly reduced (<0.05). The trophozoites were abnormal in shape, such as shrink in size, and the number of merozoites in schizonts was significantly decreased (<0.05). These results suggested that non-killing concentrations of DHA (meaning parasites can be inhibited but not killed) can significantly inhibit the growth of P. falciparum, which may not only affect the ring stage, but also have an impact on other stages of the P. falciparum.
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In view of the fact that the antimalarial effects of artemisinins are significant but the mechanism has not yet been clarified and there are many different opinions, it is possible that artemisinins can produce high anti-malarial efficacy through various mechanisms and multiple pathways. In addition, the researches on the pathogenesis of malaria "erythrocyte membrane plasmodial surface anion channel (PSAC)" in the past few years have provided more positive findings, which may confirm and discover the new antimalarial mechanism of artemisinins. This paper was as to study the effect of dihydroartemisinin (DHA) in vitro on erythrocyte membrane permeability of HB3 plasmodium infection, with using the mechanism of 5% sorbitol can be used to kill the Plasmodium falciparum in red blood cell membrane selectively, the effectual difference of sorbitol on the killing of P. falciparum with adding DHA or not was detected, so as to investigate whether DHA can affect the permeability of the erythrocyte membrane. Result showed that, Pre-stimulation with 10 nmol·L⁻¹ DHA (the final concentration of plasmodium in vitro culture system) for 30 min could significantly decrease the killing effect of sorbitol on the HB3 plasmodium in the P. falciparum erythrocytic cycle, and DHA may inhibit the permeability of the erythrocyte membrane for preventing sorbitol through the red blood cell membrane, thereby reducing the killing effect of sorbitol on the P. falciparum.
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Cerebral malaria (CM) is the leading cause of death in children under 5 years in Africa, severe neurological sequelae may occur in surviving children. Although artesunate has made breakthrough progress in the clinical treatment of CM, the clinical problems of high mortality and high morbidity have not yet been completely resolved. In this study, an experimental cerebral malaria (ECM) model was established by infecting C57BL/6 mice with Pb ANKA (Plasmodium berghei ANKA) to compare parasitemia level, survival rates, and rapid murine coma behavior scale scores, cerebral microvascular obstruction, haemozoin deposition in the liver, body temperature and weight to investigate the anti-cerebral malaria effect of the artesunate compound combination. The results showed that the artesunate compound combination could improve the survival rate of Pb ANKA-infected mice, reduce the level of parasitemia, effectively improve the symptoms of ECM neurological injury, reduce cerebrovascular obstruction and haemozoin deposition in the liver, and also significantly improve body temperature, weight and other basic indicators. The results showed that the artesunate compound combination improved the pathological changes and neurological damage caused by CM. It is expected to provide a theoretical basis for human cerebral malaria patients in clinical adjuvant therapy.
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Objective To explore the application value of sedation-agitation scale (SAS) in broncoscopy in children by observing sedative drug dosage, adverse reactions and operator's satisfaction. Methods Children were divided into two groups, control group and SAS group, before broncoscopy. Midazolam was given a dose 0.10 ~ 0.30 mg/kg according to doctor's experience, without any assessment, while the SAS group were given an initial doses of Midazolam 0.10 mg/kg and then continued giving Midazolam until the SAS score reached 3 points to 4 points, but the maxium does less than 10 mg. The maxium dosage of Midazolam in both groups was less than 10 mg. Then compare the dosage and adverse reactions of Midazolam and operator's satisfaction between the two groups. Results 606 children were enrolled in the study, 364 were boys and 242 were girls. The age ranged from 1 month to 17 years, while the mean age was (3.97 ± 3.94) years. The body weights were from 2.4 kg to 56.0 kg, and the mean weight was (16.18 ± 10.65) kg. 301 children were included into control group and 305 children were included into SAS group. The gender composition, age range, department source and composition of the diseases of the two groups were compared, and the differences were not statistically significant. Compared with the control group, there was no severe adverse reaction such as respiratory depression or excessive sedation in the SAS group, and the average amount of Midazolam was lower than the dosage in control group [(0.21 ± 0.06) vs (0.26 ± 0.05) mg/kg];the intraoperative agitation, delirium, other adverse drug reactions and the number of involved in the operation, and operation time were reduced, while the differences were statistically significant. The operator's satisfaction is higher, but the difference was not statistically significant. Conclusions SAS can be used in assessment of conscious sedation level in children's bronchoscopy, and SAS can guide the individual use of Midazolam, reduce its dosage and adverse reactions,also can improve the operator's satisfaction during the operation. SAS is worthy of application in children's conscious sedation in bronchoscopy.
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Cerebral malaria (CM), a severe neurological syndrome caused by Plasmodium falciparum infection, is a serious life-threatening disease with a high mortality. Survivors' persistent brain injury is manifested as long-term neurocognitive disorders. The main neuropathological feature of CM is the sequestration of parasited red blood cells (pRBCs) in cerebral microvessels. Other neuropathological features of CM include petechial hemorrhage in the brain parenchyma, annular hemorrhage, extensive brain endothelial cell activation, and focal endothelial cell injury and necrosis. However, its pathogenesis is still not clear. Currently, some studies have suggested that the pathogenesis of cerebral malaria mainly include pRBC adhesion, inflammatory reaction cascade, vascular leakage damage and brain hypoxia. Studies have shown that the biomarkers currently used as diagnostic and prognostic markers for CM include C-X-C motif chemokine ligand 10 (CXCL10), CXC chemokine ligand 4 (CXCL4), angiopoietin (Ang). In this paper, we systematically summarize the basic and clinical research for cerebral malaria in recent years and the latest literatures for drug studies, and focused on the advance of studies on cerebral malaria and its immunologic mechanism in the recent three years in the aspects of cytokines, immune cells, regulatory factors and biomarkers, so as to provide references for relevant studies.
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Taking mesoporous molecular sieve MCM-41 as a substrate, baicalin (BA) as template, acrylamide (AM) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linking agent, ethanol as solvent, under thermal polymerization initiator of azobis isobutyronitrilo (AIBN) , a kind of selective recognition of baicalin surface molecularly imprinted polymer was synthesized. The surface morphologies and characteristics of the MIPs were characterized by infrared spectroscopy (IR) and transmission electron microscope (TEM). The adsorption properties of polymer microsphere for the template were tested by the dynamic adsorption equilibrium experiments and static adsorption equilibrium experiments. The experiment showed that the imprinting process was successfully and the well-ordered one-dimensional pore structure of MCM-41 was still preserved. Furthermore, molecularly imprinted polymers had higher selective ability for BA, then provided a new method for the efficient separation and enrichment of baicalin active ingredients from medicinal plants Scutellaria baicalensis.
Subject(s)
Adsorption , Drugs, Chinese Herbal , Chemistry , Flavonoids , Chemistry , Molecular Imprinting , Polymerization , Polymers , Chemistry , Porosity , Scutellaria baicalensis , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To study the changes of Hes-1, the target gene of Notch signaling pathway, and its relationship with airway inflammation and remodeling in a rat model of asthma.</p><p><b>METHODS</b>Forty-eight rats were randomly divided into an asthma group and a control group. The rats in the asthma group were sensitized and challenged by ovalbumin (OVA), and normal saline was used in the control group. Two groups were further divided into 3 subgroups according to time points after challenging, i.e. 4 weeks, 8 weeks and 12 weeks (n=8 rats each). Pathological changes of lungs were observed by light microscopy and the thickness of bronchial smooth muscle layer (Wam) was measured. The levels of IL-4 and INF-γ in rat serum and bronchoalveolar lavage fluids (BALF) were measured using ELISA. Expression levels of Hes-1 protein and mRNA were determined by immunohistochemistry and quantitative real-time PCR respectively.</p><p><b>RESULTS</b>Together with the extension of challenging, the Wam of rats in the asthma group increased, a decrease of INF-γ level and an increase of IL-4 level in serum and BALF were also observed, and the differences were statistically significant compared with those in the corresponding control group (P<0.05). Hes-1 protein and mRNA levels also increased gradually after OVA challenging and were higher than those in the control group (P<0.05). The levels of Hes-1 protein and mRNA were positively correlated with Wam and IL-4 in serum and BALF, but were inversely correlated with INF-γ in serum and BALF (P<0.05).</p><p><b>CONCLUSIONS</b>Levels of Hes-1 protein and mRNA increased, which were closely related with the levels of airway inflammatory factors and remodeling of airway smooth muscle. Hes-1 may play an important role in the pathogenesis of asthma.</p>