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Ossification of the spinal ligaments (OSL) is characterized by the appearance of pathologic bone tissue within the spinal ligamentous tissue. OSL tends to occur in the cervical and thoracic segments with important cause of spinal stenosis. Compression of the spinal cord or nerve roots by ossified masses can lead to severe neurological dysfunction, which has a tremendous impact on the quality of life of patients. However, the exact etiology and pathogenesis of OSL are still unclear. Epigenetic regulation is widespread in organisms and refers to the appearance of heritable changes in gene expression without alteration in genomic DNA sequence. As an important form of biodiversity regulation, epigenetic regulation plays an important role in development of several diseases. Epigenetic regulation has multiple manifestations in OSL, including DNA methylation, histone modifications, and non-coding RNA regulation. Sequencing tools, such as gene microarrays, have revealed significant differences in DNA methylation profiles and non-coding RNA expression between ossified and normal spinal ligaments. These differences can cause abnormal expression of osteogenesis-related target genes through direct or indirect pathways, thus affecting the ossification process of spinal ligaments. In addition, interactions between these epigenetic regulatory mechanisms constitute a large and complex regulatory network. Consequently, an in-depth understanding of the role of different epigenetic regulatory mechanisms and the linkages between them in the initiation and progression stages of OSL is expected to provide a valuable reference for the clinical diagnosis and treatment of OSL-related diseases.
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ObjectiveTo analyze changes of the chemical composition in Euodiae Fructus before and after processing with Coptidis Rhizoma decoction， so as to provide scientific basis for elucidating the processing mechanism of this decoction pieces. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS） was performed on a Titank C18 column （2.1 mm×100 mm， 1.8 μm）， the mobile phase was 0.1% formic acid aqueous solution-acetonitrile for gradient elution， the column temperature was set at 40 ℃， the flow rate was 0.25 mL·min-1. Electrospray ionization （ESI） was used to scan in positive and negative ion modes， and the scanning range was m/z 50-1 250. The chemical constituents in Euodiae Fructus were identified before and after processing by reference substance comparison， database matching and literature reference， and MarkerView™ 1.2.1 software was used to normalize the obtained data， SIMCA-P 14.1 software was employed to perform principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） on MS data of raw and processed products to screen the differential components before and after processing. ResultA total of 50 compounds were identified， including 48 kinds of stir-fried products with Coptidis Rhizoma decoction and 44 kinds of raw products. After processing， six compounds were added， including danshensu， noroxyhydrastinine， oxyberberine， 13-methylberberrubine， protopine and canadine. However， two kinds of compounds， including （S）-7-hydroxysecorutaecarpine and wuchuyuamide Ⅱ， were not detected after processing. In general， after processing， the overall contents of phenolic acids and flavonoids decreased significantly， the overall content of limonoids increased， and the overall content of alkaloids did not decrease insignificantly. The results of PCA and OPLS-DA showed that there were significant differences in the composition and content of the chemical components of Euodiae Fructus before and after processing， and a total of 12 variables such as quercetin， dihydrorutaecarpine and dehydroevodiamine were obtained by screening. ConclusionEuodiae Fructus stir-fried with Coptidis Rhizoma decoction mainly contains phenolic acids， flavonoids， limonoids and alkaloids. The composition and content of the chemical components have some changes before and after processing. The addition of processing excipients and hot water immersion are the main reasons for the difference， which can provide experimental basis for interpretation of the processing mechanism of this characteristic processed products of Euodiae Fructus.
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ObjectiveBy comparing the composition and content changes of the volatile components in Atractylodis Rhizoma before and after processing with rice-washed water， the effect of rice-washed water processing on volatile components in Atractylodis Rhizoma was investigated. MethodHeadspace-gas chromatography-mass spectrometry （HS-GC-MS） was used to detect the volatile components in rhizomes of Atractylodes chinensis and A. lancea， and their processed products of rice-washed water. Chromatographic conditions were programmed temperature （starting temperature of 50 ℃ for 2 min， rising to 120 ℃ with the speed of 10 ℃·min-1， then rising to 170 ℃ at 2.5 ℃·min-1， and rising to 240 ℃ at 10 ℃·min-1 for 3 min）， the inlet temperature was 280 ℃， the split ratio was 10∶1， and the solvent delay time was 3 min. The conditions of mass spectrometry were electron bombardment ionization （EI） with ionization temperature at 230 ℃ and detection range of m/z 20-650. Then the relative content of each component was determined by the peak area normalization method. SIMCA 14.1 software was used to perform unsupervised principal component analysis （PCA） and supervised orthogonal partial least squares-discriminant analysis （OPLS-DA） on each sample data， the differential components of Atractylodis Rhizoma and its processed products were screened by the principle of variable importance in the projection （VIP） value>1. ResultA total of 60 components were identified， among which 40 were rhizomes of A. chinensis and 38 were its processed products， 46 were rhizomes of A. lancea and 47 were its processed products. PCA and OPLS-DA showed that the 4 kinds of Atractylodis Rhizoma samples were clustered into one category respectively， indicating that the volatile components of the two kinds of Atractylodis Rhizoma were significantly changed after processing with rice-washed water， and there were also significant differences in the volatile components of rhizomes of A. lancea and A. chinensis. The compound composition of Atractylodis Rhizoma and its processed products was basically the same， but the content of the compounds was significantly different. The differential components were mainly concentrated in monoterpenoids and sesquiterpenoids， and the content of monoterpenoids mostly showed a decreasing trend. ConclusionAfter processing with rice-washed water， the contents of volatile components in rhizomes of A. lancea and A. chinensis are significantly changed， and pinene， 3-carene， p-cymene， ocimene， terpinolene， atractylon， acetic acid and furfural can be used as difference markers before and after processing.
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ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution （A）-acetonitrile （B）as mobile phase for gradient elution （0-0.01 min， 20%B； 0.01-5 min， 20%-40%B； 5-40 min， 40%-95%B； 40-42 min， 95%B； 42-42.1 min， 95%-20%B； 42.1-45 min， 20%B）， electrospray ionization （ESI） was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3， the components were identified according to the primary and secondary MS data， and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1， the MS data were analyzed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode， including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water， and 10 differential components （alisol B 23-acetate， alisol I， alismol， 11-deoxy-alisol B 23-acetate， alisol B， alisol C， 11-deoxy-alisol B， alisol G， 11-deoxy-alisol C and alisol A） were screened， and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing， and the difference of substituents is the main reason for this differences， which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.
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ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution （A）-acetonitrile （B）as mobile phase for gradient elution （0-0.01 min， 20%B； 0.01-5 min， 20%-40%B； 5-40 min， 40%-95%B； 40-42 min， 95%B； 42-42.1 min， 95%-20%B； 42.1-45 min， 20%B）， electrospray ionization （ESI） was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3， the components were identified according to the primary and secondary MS data， and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1， the MS data were analyzed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode， including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water， and 10 differential components （alisol B 23-acetate， alisol I， alismol， 11-deoxy-alisol B 23-acetate， alisol B， alisol C， 11-deoxy-alisol B， alisol G， 11-deoxy-alisol C and alisol A） were screened， and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing， and the difference of substituents is the main reason for this differences， which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.
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ObjectiveBy comparing the composition and content changes of the volatile components in Atractylodis Rhizoma before and after processing with rice-washed water， the effect of rice-washed water processing on volatile components in Atractylodis Rhizoma was investigated. MethodHeadspace-gas chromatography-mass spectrometry （HS-GC-MS） was used to detect the volatile components in rhizomes of Atractylodes chinensis and A. lancea， and their processed products of rice-washed water. Chromatographic conditions were programmed temperature （starting temperature of 50 ℃ for 2 min， rising to 120 ℃ with the speed of 10 ℃·min-1， then rising to 170 ℃ at 2.5 ℃·min-1， and rising to 240 ℃ at 10 ℃·min-1 for 3 min）， the inlet temperature was 280 ℃， the split ratio was 10∶1， and the solvent delay time was 3 min. The conditions of mass spectrometry were electron bombardment ionization （EI） with ionization temperature at 230 ℃ and detection range of m/z 20-650. Then the relative content of each component was determined by the peak area normalization method. SIMCA 14.1 software was used to perform unsupervised principal component analysis （PCA） and supervised orthogonal partial least squares-discriminant analysis （OPLS-DA） on each sample data， the differential components of Atractylodis Rhizoma and its processed products were screened by the principle of variable importance in the projection （VIP） value>1. ResultA total of 60 components were identified， among which 40 were rhizomes of A. chinensis and 38 were its processed products， 46 were rhizomes of A. lancea and 47 were its processed products. PCA and OPLS-DA showed that the 4 kinds of Atractylodis Rhizoma samples were clustered into one category respectively， indicating that the volatile components of the two kinds of Atractylodis Rhizoma were significantly changed after processing with rice-washed water， and there were also significant differences in the volatile components of rhizomes of A. lancea and A. chinensis. The compound composition of Atractylodis Rhizoma and its processed products was basically the same， but the content of the compounds was significantly different. The differential components were mainly concentrated in monoterpenoids and sesquiterpenoids， and the content of monoterpenoids mostly showed a decreasing trend. ConclusionAfter processing with rice-washed water， the contents of volatile components in rhizomes of A. lancea and A. chinensis are significantly changed， and pinene， 3-carene， p-cymene， ocimene， terpinolene， atractylon， acetic acid and furfural can be used as difference markers before and after processing.
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OBJECTIVE@#To investigate the antileukemia activity of phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 on human leukemia cell line U937.@*METHODS@#MTT, soft agar assay, flow cytometric analysis and western blot were used to detect the effect of ZSTK474 on U937 cell proliferation, tumorigenicity, cell cycle, cell apoptosis and phosphorylation levels of the key factor of PI3K/AKT pathway. Chou-Talalay method was used to evaluate the combination of ZSTK474 with Cytarabine or Homoharringtonine.@*RESULTS@#PI3K inhibitor ZSTK474 could inhibit the proliferation and tumorigenicity of U937 cell, induce G@*CONCLUSION@#ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Glycogen Synthase Kinase 3 beta , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Triazines , U937 CellsABSTRACT
Objective:To evaluate the effect of methane on acetaminophen-induced acute liver injury (ALI) in mice and the role of autophagy.Methods:Forty clean-grade SPF healthy adult male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), group ALI, methane-rich saline group (group MS) and methane-rich saline plus 3-methyladenine (3-MA) group (group MS+ 3-MA). Acetaminophen 300 mg/kg was injected intraperitoneally to establish ALI model.Group MS was injected intraperitoneally with methane-rich saline 10 ml/kg immediately after establishing the model and at 12 h after establishing the model.Group MS+ 3-MA was injected intraperitoneally with methane-rich saline 10 ml/kg and autophagy inhibitor 3-MA 30 mg/kg immediately after establishing the model and was injected intraperitoneally with methane-rich saline 10 ml/kg at 12 h after establishing the model.The equal volume of sterile saline was given intraperitoneally at the same time points in C and ALI groups.At 24 h after establishment of the model, blood samples from the eyeball were taken for measuring concentrations of alanine transaminase (ALT) and aspartate transaminase (AST) in serum (using biochemistry analyzer) and the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum (using enzyme-linked immunosorbent assay). The animals were then sacrificed and liver tissues were removed for determination of microtubule-associated protein 1 light chain 3 (LC3) and p62 (by Western blot) and for the examination of the number of autophagosomes (under a transmission electron microscope). Results:Compared with group C, the concentrations of ALT, AST, TNF-α and IL-6 in serum were significantly increased, LC3Ⅱ/LC3Ⅰ ratio was increased, expression of p62 was up-regulated, and the number of autophagosomes was increased in liver tissues in ALI, MS and MS+ 3-MA groups ( P<0.05). Compared with group ALI, the concentrations of ALT, AST, TNF-α and IL-6 in serum were significantly decreased, LC3Ⅱ/LC3Ⅰ ratio was increased, expression of p62 was down-regulated, and the number of autophagosomes in liver tissues was increased in group MS, and AST concentration in serum was decreased and LC3Ⅱ/LC3Ⅰ ratio was increased in group MS+ 3-MA ( P<0.05). Compared with group MS, the concentrations of ALT, AST, TNF-α and IL-6 were significantly increased, the LC3 II/LC3 I ratio and the number of autophagosomes were decreased in lung tissues in group MS+ 3-MA ( P<0.05). Conclusion:The mechanism by which methane can reduce acetaminophen-induced ALI is related to enhancement of the level of autophagy in liver cells in mice.
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Department operation analysis is the basis of delicacy management of hospitals. This paper briefly presented the problems existing in conventional department operation analysis, and proposed solutions to overcome such problems, using department operation analysis based on the perspective of business-finance integration. Taking the image center of a large general hospital as an example, based on the concept of business-finance integration, the paper used process analysis and benchmarking comparison method to explore operation analysis and put forward suggestions for department operation improvement. The establishment of a department operation management system combined with business can improve the level of delicacy management and promote the long-term and stable development of the hospital.
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The aim of this study was to investigate the regulatory role of retinoid X receptor (RXR)-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury (PIRI) and the underlying mechanism. Seventy-seven male Sprague-Dawley (SD) rats were randomly divided into 7 groups (n = 11): control group, sham group, sham+9-cis-retinoid acid (9-cRA, RXR agonist) group, sham+HX531 (RXR inhibitor) group, ischemia/reperfusion (I/R) group, I/R+9-cRA group, and I/R+HX531 group. The unilateral lung I/R model was established by obstruction of left lung hilus for 30 min and reperfusion for 180 min in vivo. The rats in I/R+9-cRA and I/R+HX531 groups were given intraperitoneal injection of 9-cRA and HX531 before thoracotomy. After reperfusion, the left lung tissue was taken to evaluate the lung tissue injury, and the oxidative stress-related indexes of the lung tissue were detected by the corresponding kits. The lung tissue morphology and the ultrastructure of the alveolar epithelial cells were observed by HE staining and transmission electron microscope, respectively. The protein expression of RXR in lung tissue was observed by immunofluorescence labeling method, and the expression level of nuclear factor E2-related factor (Nrf2) protein was detected by Western blot. The results showed that, compared with the sham group, the I/R group exhibited obviously injured lung tissue, decreased SOD activity, increased MDA content and MPO activity, and down-regulated expression level of Nrf2 protein. Compared with the I/R group, the I/R+9-cRA group showed alleviated lung tissue injury, increased activity of SOD, decreased MDA content and MPO activity, and up-regulated expression levels of RXR and Nrf2 protein. The above-mentioned improvement effects of 9-cRA were reversed by HX531 treatment. These results suggest that RXR activation can effectively protect the lung tissue against I/R injury, and the mechanism may involve the activation of Nrf2 signaling pathway, the enhancement of antioxidant level and the reduction of oxidative stress response.
Subject(s)
Animals , Male , Rats , Lung , NF-E2-Related Factor 2 , Physiology , Oxidative Stress , Random Allocation , Rats, Sprague-Dawley , Reperfusion Injury , Retinoid X Receptors , Physiology , Signal TransductionABSTRACT
The neuropeptide orexin is widely distributed in the nervous system. Previous studies showed that orexin is involved in the feeding behavior regulation by binding to its receptor 1 (OX1R) and receptor 2 (OX2R) to activate the downstream signaling pathway. Recent studies have demonstrated that the system of orexin and its receptors are also involved in important physiological processes such as sleep-wake, learning and memory, and pathological processes of various neurological diseases. In this review, we summarized the research progress on the function of the orexin and its receptor system in physiological and pathological processes, and revealed the correlation between orexin and nervous system diseases, in order to provide the theoretical guidance for the diagnosis and treatment of the related diseases in the future.
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Humans , Nervous System Diseases , Orexin Receptors , Physiology , Orexins , Physiology , Signal TransductionABSTRACT
OBJECTIVE@#To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice.@*METHODS@#Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot.@*RESULTS@#Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA.@*CONCLUSIONS@#The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.
Subject(s)
Animals , Male , Mice , Apoptosis , Caspase 12 , Caspase 3 , Metabolism , Creatine Kinase, MB Form , Blood , Endoplasmic Reticulum Stress , Heart Injuries , Heat-Shock Proteins , Metabolism , L-Lactate Dehydrogenase , Blood , Lung , Pathology , MAP Kinase Kinase 4 , Metabolism , Mice, Inbred C57BL , Myocardium , Pathology , Random Allocation , Reperfusion Injury , Transcription Factor CHOP , MetabolismABSTRACT
OBJECTIVES@#To investigate the effects of dexmedetomidine (Dex) on injury of A549 cells induced by hypoxia/reoxygenation(H/R)and the influence of C/EBP homologous protein (CHOP) expression.@*METHODS@#Logarithmic growth phase A549 cells(it originated from alveolar type Ⅱ epithelial cell line) were randomly divided into 4 groups (=10):normoxic control group (N), Dex group (D), hypoxia/reoxygenation group (H), hypoxia/reoxygenation + Dex group(HD). At the beginning of modeling, 1 nmol/L Dex was puted into D and HD groups. N and D groups were cultured in the normoxic incubator for 30 h. H and HD group were incubated in the anoxic cultivation for 6 h, fo llowed by normoxic culture for 24 h. Then A549 cells were observed under the inverted microscope to observe the morphological changes. Cell activity was detected by cell counting Kit-8(CCK-8) and the apoptosis index(AI) was detected by in situ end labeling (TUNEL) method. The expression of CHOP、glucose-regulated protein of molecular weight 78 kDa (Grp78)、cysteinyl aspirate-specificprotease-3 (caspase-3) protein and CHOP、Grp78 mRNA were detected by Western blot and RT-PCR.@*RESULTS@#Compared with N group, the number of adherent cells in H group decreased significantly, and cell morphology changed. The absorbance value in H group decreased obviously (<0. 01). The AI value and expression of CHOP, Grp78, caspase-3 proteins and CHOP, Grp78 mRNA were significantly increased (<0.01). Compared with H group, the cell damage in HD group was decreased, the absorbance value increased (<0.01), the number of apoptosis cells decreased relatively (<0.01), the expression of CHOP, caspase-3 protein and CHOP mRNA decreased (<0. 01).@*CONCLUSIONS@#Dex has notable effects against H/R injury, which may be related to effective inhibition of apoptosis mediated by the CHOP's signal path.
Subject(s)
Humans , A549 Cells , Apoptosis , Cell Hypoxia , Dexmedetomidine , Pharmacology , Transcription Factor CHOP , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg•bw•day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined.</p><p><b>RESULTS</b>There were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.</p><p><b>CONCLUSION</b>Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.</p>
Subject(s)
Animals , Female , Male , Rats , Administration, Oral , Dose-Response Relationship, Drug , Nanoparticles , Toxicity , Particle Size , Rats, Sprague-Dawley , Silicon Dioxide , Toxicity , Toxicity Tests, SubchronicABSTRACT
OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.
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Objective To explore the prospective monitoring and control methods for missing reporting of health-care-associated infection(HAI)cases,analyze its implementation efficacy,provide basis for formulating targeted strategy for monitoring missing report of HAI.Methods From January 2016 to June 2017,the quality control circle (QCC)method was used to prospectively monitor HAI cases in hospitalized patients,missing reporting of HAI was controlled.Results "Information system intelligence screening+mobile messaging alerts+ HAI supervision"trinity monitoring model for avoid missing reporting of HAI cases was established,after the first round of PDCA(plan, do,check,action)cycle,missing reporting rate of HAI decreased from 79.16% before QCC to 59.75% after QCC, difference was statistically significant (χ2＝208.821,P＝0.000).Compared with missing reporting rate of HAI af-ter the first round of PDCA,missing reporting rate of HAI after the second round of PDCA dropped to 26.18%, difference was statistically significant (χ2＝200.075,P＝0.002).Conclusion Active prospective prevention and control before missing reporting of HAI can effectively avoid missing reporting of HAI cases.
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Objective To investigate the effect of full nutrition management on cancer patients with chemotherapy, and to support theory bases for the standardized clinical nutrition of cancer patients. Methods From January 2016 to December 2017, a total of 88 patients with the first chemotherapy were recruited and randomly divided into experimental group and control group, with 44 patients in each group. These patients all complied with the inclusion and exclusion criteria, and volunteered for the study. The two groups all received the same of anti-tumor treatment and the same conventional nutritional support (according to the results of nutrition screening and nutrition assessment, the nutritional support was formulated and patients′dietary guidance was given), while only patients of the experimental group were given full nutritional management, including regularly following up the patient′s condition changes, gastrointestinal reactions, and the feed. According to the five-step treatment model of malnutrition, nutritional support was improved in a timely manner, and appropriate nutritional support was provided. At the end of chemotherapy, the change of weight, albumin, prealbumin, hemoglobin was compared with that before treatment in the two groups. Results After chemotherapy, albumin, prealbumin, hemoglobin had no obvious drop compared with that before treatment in two groups (P>0.05). The patients of experimental group showed stable weight after chemotherapy: (53.39 ± 9.24) kg vs. (54.66 ± 9.41) kg, P>0.05. Weight loss in the control group after chemotherapy was statistically significant:(54.61 ± 10.76) kg vs. (56.52 ± 10.46) kg, P<0.05. Conclusions The full nutritional management can help maintain nutrition status during chemotherapy, especially can prevent the weight loss.
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Objective@#To retrospectively analyze the serum calcium level in sepsis patients, understand the influencing factors of abnormality calcium metabolism, and analyze the effect of serum calcium level on sepsis prognosis.@*Methods@#From January 1, 2017 to January 31, 2018, clinical data about sepsis patients admitted hospital were collected. The patients were divided into 2 groups according the levels of serum calcium measured in patients admitted in 24 h: normal serum calcium group (serum calcium 2.03-2.67 mmol/L), and low serum calcium group (serum calcium<2.03 mmol/L). And this study did not find hypercalcemia patients. The data about laboratory test index were compared between two groups.@*Results@#Fifty-two cases were included in this study, including 14 cases of normal serum calcium and 38 cases of hypocalcemia, and the incidence rate of hypocalcemia was 73.1%(38/52). The level of serum calcium in hypocalcemia group was (1.78 ± 0.17) mmol/L, and was (2.16 ± 0.14) mmol/L in normal serum calcium group. The main position of infections in patients with sepsis were digestive system, respiratory system and urinary system. Compared with that in the normal serum calcium group, the number of malnutrition patients in the hypocalcemia group was more. The total protein (TP), albumin (ALB), prealbumin (PAB) and total cholesterol (TCH) in the nutritional status of the patients were lower, the sequential organ failure assessment (SOFA) scores was higher, the prothrombin activity (PTA) was lower, the prothrombin time (PT) was prolonged, and international normalized ratio (INR) was increased. The differences were statistically significant (P<0.05 or <0.01). Pearson correlation test was used to screen the tests and scores related to the concentration of serum calcium. The results showed that the serum calcium concentration was negatively correlated with the level of SOFA scores, procalcitonin (PCT), PTA, thrombin time (PT), activated partial thromboplastin time (APTT) and INR (r=- 0.431, - 0.361, - 0.441, - 0.431, - 0.427, - 0.420, P<0.01 or<0.05), and the serum calcium concentration was positively correlated with TCH, TP, ALB and PAB (r=0.442, 0.475, 0.463, 0.419, P<0.01).@*Conclusions@#Hypocalcemia is related to the nutritional status of the body, and is related to coagulation function, serum protein level, PCT concentration and SOFA scores. The decrease of serum calcium indicates that multiple organ dysfunction syndrome may occur, and should be paid more attention to.
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AIM:To investigate the protein expression of mitogen-activated protein kinase-interacting kinase-2 (Mnk2) and its prognostic effect in the patients with resected esophageal squamous cell carcinoma (ESCC).METHODS:A total of 86 informative patients with surgically resected ESCC and 54 normal esophageal tissues were enrolled .Western blot and immunohistochemistry (IHC) were utilized to assess the protein expression of Mnk 2, and its correlation with prog-nosis was statistically analyzed by the methods of Kaplan-Meier curve and Cox proportional hazard mode .RESULTS:The protein expression of Mnk 2 was elevated in most of tumor tissues compared with the adjacent tissues .Clinicopathologic analysis showed that Mnk2 expression was significantly correlated with the TNM stage (P<0.05).Both disease-free sur-vival ( DFS) and overall survival ( OS) of Mnk2 over-expression patients were shorter than those in Mnk 2 negative expres-sion group.Multivariate analysis confirmed that Mnk2 expression, as an independent and significant factor for both DFS and OS, predicted a poor prognosis of the patients with resected ESCC (P<0.05).CONCLUSION: The expression of Mnk2 was significantly related to the TNM stages , and might be a novel predictor for prognosis in ESCC .
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The purpose of the present study was to investigate the effect of excessive endoplasmic reticulum stress (ERS) on the brain damage in hypoxia hypercapnia induced pulmonary hypertension (HHPH) rats. Forty healthy SPF male SD rats were randomly divided into four groups (n = 10 for each): control group, hypoxia hypercapnia group, ERS pathway agonist tunicamycin (TM) group and ERS pathway inhibitor 4-phenylbutyric acid (4-PBA) group. The rats of control group lived in normal environment, while the rats of other three groups were raised for four weeks in the tank with 8.5%-11% Oand 5%-6% CO. TM (0.08 mg/kg, twice a week) and 4-PBA (80 mg/kg, daily) were respectively intraperitoneally injected into the rats of TM and 4-PBA groups, and the hypoxia hypercapnia group was given the same volume of normal saline. The mean pulmonary artery pressure and heart perfusion of the rats were determined and recorded after four-week raising. Then the brain tissue of the rats were quickly taken out for the brain water content measuring and morphological changes observing. The Caspase-3 activity and the apoptotic index of the brain cells were also determined. The protein and mRNA expressions of p-JNK, Caspase-12, CHOP and GRP78 in brain tissues were detected by Western blot and RT-PCR. The results showed that compared with the control group, the mean pulmonary artery pressure, brain water content and brain cells apoptotic index, Caspase-3 activity, the protein and mRNA levels of p-JNK, Caspase-12, CHOP and GRP78 were increased (P < 0.05), and the brain tissues of the rats were obviously damaged in the rats raised in the hypoxia hypercapnia environment; compared with hypoxia hypercapnia group, the mean pulmonary artery pressure, brain water content, brain apoptotic index and Caspase-3 activity, p-JNK, Caspase-12, CHOP, GRP78 protein and mRNA expressions in TM group were increased (P < 0.05), and the brain tissues of the rats were obviously damaged, while all above changes were relieved in 4-PBA group (P < 0.05). These results suggest that excessive ERS may participate in the brain injury induced by HHPH in rats and inhibition of excessive ERS can relieve the brain injury in the rats with HHPH.