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Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.
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Candida albicans as a pathogen of great clinical significance can widely colonize in many ecological niches of human body, especially in the immunocompromised population. Currently, antifungal drugs that can be used in clinical treatment are very limited. However, the genome of Candida albicans has a high rate of mutation, which can help it quickly develop resistance to antifungal drugs. Therefore, drug resistance in Candida albicans remains a great threat to clinical practice. This article focused on the frequent loss of heterozygosity (LOH) events in Candida albicans, summarized the association between LOH and other genomic variants and discussed the relationship of the frequency of de novo mutations, heterozygous status of key drug resistance genes and reproductive pattern with antifungal drug resistance.
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Objective:To investigate the risk factors for combined coronary microvascular dysfunction (CMD) in patients with ischemia and non-obstructive coronary artery disease (INOCA).Methods:From October 2020 to May 2022, 100 INOCA patients with myocardial ischemic symptoms who underwent coronary angiography (CAG) suggestive of <50% stenosis in all three coronary arteries at the Tenth People′s Hospital of Tongji University were prospectively recruited. Myocardial perfusion imaging (MPI), transthoracic echocardiography and cadmium-zinc-telluride (CZT) SPECT coronary flow quantification were performed in the same month, and 93 INOCA patients (36 males and 57 females, age (63.0±10.9) years) were finally included. CMD was defined as coronary flow reserve (CFR)<2.5. Independent-sample t test, Mann-Whitney U test and χ2 test were used to compare MPI results and left ventricular volume parameters between CMD and non-CMD groups. ROC curve analysis was used to analyze the efficacy of each index in predicting CMD, and independent risk factors for CMD were screened by multivariate logistic regression analysis. Results:Among 93 INOCA patients, 29 were in the CMD group and 64 were in the non-CMD group. The age, proportion of hypertension, left ventricular mass index (LVMI), summed stress score (SSS), summed difference score (SDS), left ventricular internal diameter systolic (LVIDS), interventricular septum thickness (IVST), and left ventricular posterior wall thickness (LVPWT) in the CMD group were higher than those in the non-CMD group ( t values: 2.42-3.76, χ2=8.94, z values: -3.31, -3.41, all P<0.05). ROC curve analysis showed that LVMI, SSS, SDS, LVPWT, IVST and age were significant in predicting CMD (AUCs: 0.67-0.72). Multivariate logistic regression analysis showed that LVMI (odds ratio ( OR)=1.08, 95% CI: 1.01-1.17), SDS ( OR=5.37, 95% CI: 1.95-14.78), hypertension ( OR=5.68, 95% CI: 1.34-24.18) and age ( OR=1.10, 95% CI: 1.03-1.18) were risk factors for CMD. Conclusion:LVMI, SDS, hypertension and age are strongly associated with combined CMD in INOCA patients, which can be used for early risk stratification of INOCA patients.
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Objective To analyze the equity and efficiency of resource allocation for management and treatment of severe mental disorders in Shanghai in 2020, and to provide a foundation for making relevant policies. Methods Data on resource allocation for the management and treatment of severe mental disorders in 17 district-level mental health institutions in 2020 were collected. The Gini coefficient was used to evaluate the equity of resource allocation by population and geographic area, and data envelopment analysis was carried out to analyze the equity of resource allocation. Results The Gini coefficients of special funds, psychiatric medical staff and actual open beds according to population were 0.24, 0.25 and 0.27, respectively. The Gini coefficients according to area were 0.54, 0.62 and 0.64, respectively. The average efficiency of resource allocation was 0.865. There were 5 institutions where DEA was effective, accounting for 29.41%. There were 12 institutions where DEA was non-effective, accounting for 70.59%. Conclusion The equity of resources allocation for the management and treatment of severe mental disorders according to population is good, but the equity of allocation based on geographic area is not high. The efficiency of resource allocation needs to be further improved. It is suggested that the resource allocation should be optimized to promote the fairness and efficiency of resource allocation for the management and treatment of severe mental disorders.
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Objective@#To analyze the current status and equity of mental health resources allocation in Shanghai Municipality, so as to provide data supports to formulate mental health action plans and relevant policies. .@*Methods@#The data pertaining to mental health institutions, actual beds opened, certified or assistant psychiatrists and registered nurses was collected from the Survey of the Current Status on Mental Health Resources in Shanghai Municipality in 2020. The equity of mental health resources allocated by population and geographical area in Shanghai Municipality was evaluated with Lorenz curve and Gini coefficient@*Results@#There were 96 mental health institutions, 15 060 actual beds opened, 257 certified or assistant psychiatrists and 2 887 registered nurses in Shanghai Municipality in 2020, with a physician-to-nurse ratio of 1∶2.30. The greatest numbers of actual beds opened in the department of psychiatrics, the number of certified or assistant psychiatrists and the number of registered nurses per 10 000 residents and per km2 were all found the central urban areas. The numbers of actual beds opened in the department of psychiatrics, the number of certified or assistant psychiatrists and the number of registered nurses per 10 000 residents were 6.06 beds, 0.51 physicians and 1.16 nurses, with Gini coefficients of 0.36, 0.42 and 0.44, respectively, and the numbers of actual beds opened in the department of psychiatrics, the number of certified or assistant psychiatrists and the number of registered nurses per km2 were 2.38 beds, 0.20 physicians and 0.46 nurses, with Gini coefficients of 0.72, 0.76 and 0.75, respectively. @*Conclusions@#There was a gross equity in mental health resources allocated by population and geographical area in Shanghai Municipality in 2020, which showed an improvement as compared to 2015. The equity in mental health resources allocated by geographical area was lower than that by population in Shanghai Municipality.
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OBJECTIVES@#To study the serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in children with autism spectrum disorder (ASD) and their association with the core symptoms of ASD.@*METHODS@#A total of 150 ASD children aged 2-7 years (ASD group) and 165 healthy children matched for age and sex (control group) who were recruited at the outpatient service of Chongqing Health Center for Women and Children were enrolled as subjects. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the core symptoms of the ASD children. Chemiluminescence was used to measure the serum levels of IGF-1 and IGFBP-3 in both groups.@*RESULTS@#The ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). The children with severe ASD had significantly lower serum levels of IGF-1 and IGFBP-3 than those with mild-to-moderate ASD (P<0.001). For the children aged 2-3 years, the ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). Boys had a significantly lower serum level of IGF-1 than girls in both ASD and control groups (P<0.05). The serum levels of IGF-1 and IGFBP-3 were negatively correlated with the total score of CARS (r=-0.32 and -0.40 respectively, P<0.001).@*CONCLUSIONS@#The reduction in serum IGF-1 level in early childhood may be associated with the development of ASD, and the serum levels of IGF-1 and IGFBP-3 are associated with the core symptoms of ASD children.
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Child , Child, Preschool , Female , Humans , Male , Autism Spectrum Disorder , Autistic Disorder , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor IABSTRACT
Objective:To establish a program for the prevention and management of parastomal hernia in patients with ostomy.Methods:Based on literature analysis and clinical needs, combined with the individual and family self-management theory (IFSMT), a preliminary plan for prevention and management of parastomal hernia was developed with the framework of case management model. Sixteen experts were selected for two rounds of Delphi expert consultations to analyze and screen indicators at all levels to calculate the expert′s positive coefficient, authority coefficient and coordination coefficient to analyze the credibility of expert consultation results.Results:The effective recovery rates of the two rounds of expert letter inquiries were 88.89% and 100.00%, the authoritative coefficients were 0.825 and 0.844, and the two rounds of Kendall′s W values were 0.221 and 0.269, which were statistically significant( P<0.01). The concentration of indicators is high. Finally, a programe for parastomal hernia prevention and management based on the self-management theory of individual and family consisting of 6 first-level indicators,16 second-level indicators and 42 third-level indicators was obtained. Conclusion:The programe for prevention and management of parastomal hernia based on individual and family self-management theory has high reliability and scientificity, and can provide a basis for the study of parastomal hernia prevention and management.
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OBJECTIVE：To learn from pedia tric drug pricing and price incentive policy in Japan ，and to provide reference for the improvement of pediatric drug price system in China. METHODS ：The drug pricing strategy of Japan was analyzed ，and price incentive policy of pediatric drugs in Japan and its implementation status and effect were summarized. The suggestions of perfecting the price system of pediatric drugs in China were put forward . RESULTS & CONCLUSIONS ：The pricing strategy of medical insurance drugs in Japan included two types ，such as access pricing of medical insurance list and price adjustment of drugs in medical insurance list. Among them ，price incentive policy for pediatric drugs mainly included the premium for initial pricing of new pediatric drugs ，the premium for drugs with newly added pediatric indication included in medical insurance list and other measures（such as eligible drugs could obtain indirect price compensation ，and children ’s factors could be considered in health technology assessment ）. Overall ，these measures accelerated the R&D and marketing of Japanese pediatric drugs ，and effectively promoted the development of pediatric drugs in Japan. The author suggests that our country should carry out health technology assessment which reflects the particularity of pediatric drugs ，give appropriate direct price incentives to the payment price of pediatric drugs ，and reasonably set the price of drug specification suitable for children and give price incentives so as to promote the development of pediatric drugs in China.
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Radiomics has become an important means of medical imaging diagnosis. Cardiovascular diseases seriously threaten human life, and nuclear medicine has shown its unique advantages in the diagnosis of cardiovascular diseases. In this field, relevant studies on the combination of nuclear medicine and radiomics have achieved some results. The combination of two technologies has great application prospects, but there are also some challenges. This paper reviews the basic principles of radiomics, the advantages and clinical applications of nuclear medicine in the diagnosis of cardiovascular diseases, the current research status, challenges and foreground of radiomics combined with nuclear medicine in the diagnosis of cardiovascular diseases, in order to provide some useful thoughts for further research.
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OBJECTIVES@#A study was conducted to investigate the molecular mechanism of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) influencing the invasion and metastasis of tongue squamous cell carcinoma and to provide a new target for clinical inhibition of invasion and metastasis of tongue squamous cell carcinoma.@*METHODS@#Ualcan website was used to analyze the expression of CHD1L in normal epithelial tissue and primary head and neck squamous cell carcinoma and to analyze the effect of lymph node metastasis on the expression of CHD1L in tissues with head and neck squamous cell carcinoma. The relationship between CHD1L expression and the survival rate of patients with head and neck squamous cell carcinoma was tested by the GEPIA website. Western blot was used to quantify the levels of CHD1L protein in human tongue squamous cell carcinoma CAL27 and immortalized human skin keratinocyte cell HaCaT. After knocking down CAL27 in human tongue squamous cell carcinoma cells with an RNA interference plasmid, the cells were designated as SiCHD1L/CAL27 and Scr/CAL27. Western blot was utilized to detect the expression of CHD1L in each group of cells. The change in CAL27 cell proliferation ability was tested by EdU proliferation test after CHD1L knockdown. The change of cell migration ability of each group cells was tested through the wound healing assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) marker E-cadherin and Vimentin protein expression levels.@*RESULTS@#Ualcan database showed that the expression of CHD1L in primary head and neck squamous cell carcinoma tissues was higher than in normal epithelial tissues and in head and neck squamous cell carcinoma tissues with lymph node metastasis. GEPIA website analysis showed that the overall survival rate of patients with head and neck squamous cell carcinoma with high expression of CHD1L was significantly lower than that of patients with low expression. Western blot results showed that CHD1L expression in human tongue squamous carcinoma cells CAL27 was higher than that of human normal skin cells HaCaT. CHD1L expression in SiCHD1L/CAL27 cells was much lower than that in Scr/CAL27 cells. Results of EdU proliferation experiments showed the significant reduction in the cell proliferation ability of the SiCHD1L/CAL27 cells. Results of the wound healing experiments showed the reduction in the migration capacity of the SiCHD1L/CAL27 cells. The expression of E-cadherin increased, whereas that of Vimentin decreased, in SiCHD1L/CAL27 cells.@*CONCLUSIONS@#CHD1L promoted the EMT, proliferation, migration, and invasion ability of tongue squamous cell carcinoma cells.
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Humans , Adenosine Triphosphatases , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , DNA Helicases , DNA-Binding Proteins , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Neoplasm Invasiveness/genetics , Tongue , Tongue Neoplasms/geneticsABSTRACT
OBJECTIVE@#To analyze the metabolic profile and genetic variants for newborns with primary carnitine deficiency (PCD) from Guangxi, China.@*METHODS@#From January 2014 to December 2019, 400 575 newborns from the jurisdiction of Guangxi Zhuang Autonomous Region Newborn Screening Center were subjected to tandem mass spectrometry (MS/MS) analysis. Newborns with positive results for PCD and their mothers were recalled for retesting. Those who were still positive were subjected to sequencing of the SLC22A5 gene.@*RESULTS@#Twenty-two newborns and 9 mothers were diagnosed with PCD, which gave a prevalence rate of 1/18 208. Sequencing of 18 newborns and 4 mothers have identified 14 types of SLC22A5 gene variants, with the common ones including c.51C>G (10/44, 22.7%), c.1195C>T (9/44, 20.5%) and c.1400C>G (7/44, 15.9%), The c.517delC(p.L173Cfs*3) and c.1031C>T(p.T344I) were unreported previously and predicted to be pathogenic (PVS1+PM2_supporting+PM3+PP4) and likely pathogenic (PM1+PM2_supporting+PM3+PP3+PP4) based on the American College of Medical Genetics and Genomics standards and guidelines.@*CONCLUSION@#c.51C>G, c.1195C>T and c.1400C>G are the most common variants underlying PCD in Guangxi.
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Humans , Infant, Newborn , Cardiomyopathies , Carnitine/deficiency , China , Hyperammonemia , Metabolome , Muscular Diseases , Mutation , Solute Carrier Family 22 Member 5/genetics , Tandem Mass SpectrometryABSTRACT
PURPOSE@#This meta-analysis compared the clinical outcome of three-dimensional (3D) printing combined with open reduction and internal fixation (ORIF) to traditional ORIF in the treatment of acetabular fractures.@*METHODS@#We searched the Cochrane Library, PubMed, Embase, VIP database, CNKI, and Wanfang database with keywords "acetabular fracture", "3D printing", "three-dimensional printing", "open reduction and internal fixation", "Acetabulum", "Acetabula" from January 2000 to March 2020. Two reviewers independently selected articles, extracted data, assessed the quality evidence and risk bias of included trials using the Cochrane Collaboration' s tools and/or Newcastle-Ottawa scale. When the two analysts had different opinions, they would ask the third analyst for opinion. Randomized controlled trials or retrospective comparative studies of 3D printing combined with ORIF (3D printing group) versus traditional ORIF (conventional group) in the treatment of acetabular fractures were selected. The data of operation time, intraoperative blood loss, intraoperative fluoroscopy times, incidence of complications, excellent and good rate of Matta score for reduction, and excellent and good rate of hip function score were extracted. Stata14.0 statistical software was used for data analysis.@*RESULTS@#Altogether 9 articles were selected, including 5 randomized controlled trials and 4 retrospective studies. A total of 467 patients were analyzed, 250 in the conventional group, and 217 in the 3D printing group. The operation time in the 3D printing group was less than that in the conventional group and the difference was statistically significant (standardized mean difference (SMD) = -1.19, 95% CI: -1.55 to -0.82, p 0.05). There was no significant difference in the excellent and good rate of hip function score at the end of postoperative follow-up between the two groups (OR = 0.84, 95% CI: 0.46-1.56, p > 0.05), but the follow-up time varies from 6 months to 40 months.@*CONCLUSION@#Compared with traditional ORIF, 3D printing combined with ORIF has certain advantages in terms that 3D printing not only helps surgeons to understand acetabular fractures more intuitively, but also effectively reduces operation time, intraoperative blood loss, intraoperative fluoroscopy times, and postoperative complications. However, there were no significant differences in the excellent and good rate of Matta score for reduction and the excellent and good rate of hip function score at the end of follow-up.
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Objective:To elucidate the potential molecular markers and drug-compound-target mechanism of Epimedii Folium intervention on breast cancer stem cells（BCSCs） through chip analysis combined with network pharmacology and experimental validation. Method:Relevant drug information was retrieved in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） to obtain the active components and potential targets of Epimedii Folium. "Breast Cancer Stem Cells" were searched in Gene Expression Omnibus（GEO）database，and GSE98239 chip data were obtained through analysis and screening. Then GEO2R online analysis tool was used to obtain the differential genes to draw differential gene heat map and volcano map. The differential gene network map of Epimedii Folium intervention for breast cancer stem cells was constructed by Cytoscape 3.8.0，and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）enrichment analysis of drug and disease genes were performed. Human breast cancer MDA-MB-231 cells were divided into 20%，40%，60% Epimedii Folium drug-containing serum group and control group. Cell counting kit-8（CCK-8），and Western blot were used to detect the effect of Epimedii Folium drug-containing serum intervention on cell activity and target protein expression in breast cancer cells. Result:Twenty-three active components including flavones，sterols，alkaloids and sesquiterpenoids were obtained from Epimedii Folium. It was found that Epimedii Folium interacted with B-cell lymphoma-2-like protein 1（BCL2L1），matrix metallopeptidase 2（MMP2），prostaglandin-endoperoxide synthase 2（PTGS2），vascular endothelial growth factor A（VEGFA），transforming growth factor beta receptor 1（TGFBR1） and other pivotal genes in breast cancer stem cells，participated in the induction of new angiogenesis and cell migration，enabled the continuous self-renewal of BCSCs，decreased apoptosis and cell migration，thus promoting the recurrence and metastasis of breast cancer. KEGG results showed that Epimedii Folium intervened in multiple differential expressed genes（DEGs）of transforming growth factor-<italic>β</italic>（TGF-<italic>β</italic>），vascular endothelial growth factor（VEGF），phosphoinositide 3kinase/protein kenase B（PI3K/Akt），mitogen-activated protein kinese（MAPK）and mammalian target of rapamycin（mTOR）subpathways in cancer signaling pathways to exert its efficacy in intervening breast cancer stem cells. Experiments showed that the survival rate of breast cancer cells was significantly reduced and the expression levels of TGFBR1 and Smad2 in breast cancer cells significantly decreased after the intervention of Epimedii Folium drug-containing serum（<italic>P</italic><0.01）. Conclusion:Several components in different concentrations of drug-containing serum of Epimedii Folium can synergistically act on target differentially expressed genes of breast cancer stem cells，and inhibit the proliferation of breast cancer cells by down-regulating the expression levels of TGFBR1，a key molecule in the TGF-<italic>β</italic> pathway，and Smad2，a downstream signal.
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Objective:To establish the high performance liquid chromatography （HPLC） fingerprint of Citri Sarcodactylis Fructus， and to search for makers to characterize the quality difference of Citri Sarcodactylis Fructus from different origins coupled with chemometrics. Method:The analysis was performed on a Thermo Hypersil GOLD C<sub>18</sub> column （4.6 mm×250 mm， 5 μm） with mobile phase consisted of acetonitrile-0.05% phosphoric acid solution for gradient elution， and the detection wavelength was set at 254 nm. A total of 31 batches of samples were analyzed to establish the HPLC fingerprint of Citri Sarcodactylis Fructus. Similarity evaluation was performed by Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System （2012 edition） to confirm the common peaks， which were identified by comparison of reference substances. On the basis， chemometrics methods were used to analyze and evaluate the quality of Citri Sarcodactylis Fructus from different origins. At the same time， 3 batches of 5 species of decoction pieces from the genus <italic>Citrus</italic> in the family Rutaceae， including Citri Sarcodactylis Fructus， Aurantii Fructus Immaturus， Aurantii Fructus， Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium， were randomly collected for evaluating the effectiveness and reliability of the established HPLC fingerprint of Citri Sarcodactylis Fructus. Result:HPLC fingerprint of Citri Sarcodactylis Fructus was established and 22 common peaks were identified. And seven common peaks among them were identified as 6，7-dimethoxycoumarin， diosmin， hesperidin， byakangelicin， 5，7-dimethoxycoumarin， bergapten and oxypeucedanin. Except for 2 batches of samples， the similarities of fingerprints between other 29 batches of samples were >0.9. The 31 batches of Citri Sarcodactylis Fructus were basically divided into 3 groups by cluster analysis and principal component analysis， which were consistent with the classification of three different producing areas. Eight differential markers were screened by orthogonal partial least squares discriminant analysis and four of them （5，7-dimethoxycoumarin， bergapten， 6，7-dimethoxycoumarin and diosmin） were identified by reference substances. Similarity evaluation of 5 species of decoction pieces from genus <italic>Citrus</italic> in the family Rutaceae was carried out by taking the reference fingerprint of Citri Sarcodactylis Fructus as treference chromatogram， similarity of Citri Sarcodactylis Fructus decoction pieces was 0.892-0.977， and the similarities of the other 4 kinds of decoction pieces were 0.215-0.517. Conclusion:The established fingerprint method is reasonable， effective and accurate for quality control of Citri Sarcodactylis Fructus， the characterization information is more comprehensive combined with chemometrics.
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OBJECTIVE：To evaluate the application effects of wh ole process intelligent dispensing mode in the inpatient pharmacy of our hospital ，and to provide reference for the intelligent construction of pharmacy department. METHODS ：Combined with the working situation of inpatient pharmacy in our hospital ，the application of automated drug unit-dose dispensing machine （ADDM），intelligent tablet dispensing table （ITDT），medication detection machine （MDM）were introduced. The improvement of work efficiency and the error rate were compared with before and after the implementation of intelligent dispensing mode. The satisfaction survey of intelligent mode was carried out. RESULTS ：Under the dispensing linkage mode of ADDM+ITDT+MDM ， the time of oral drug dispensing was shortened by about 1.5 h per person ；pharmacists reduced by 2 persons；with the help of ADDM image database and image printing technology of drug bag ，the visual inspection method and the efficiency of drug check could be improved ；the introduction of ITDT standardized the management of dismounted drug ，and the work efficiency of dispensing dismounted drug by ITDT （daily dispensing back-up time as index ）were improved 23.29％-38.93％，compared with manual dispensing. The introduction of MDM improved the efficiency of intelligent check ，all drug information could be traced ， and the work efficiency [daily （total）check time as index] were 65.64％-74.78％ higher than that of manual check ；the error rate of three machine dispensing linkage mode was 70.32％ lower than that of ADDM+manual check and dispensing mode ，52.44％ lower than that of ADDM+MDM linkage mode ，and the overall satisfaction of nu rsing staff was 97.97％. CONCLUSIONS ： ADDM+ITDT+MDM linkage mode shortens dispensing time ， ＊副主任药师 。研究方向 ：医院药学 。电话：0571-56007192。 E-mail：61012796@qq.com improves work efficiency and decreases error rate. # 通信作者 ：副主任药师 。研究方向 ：医院药学 。电话：0571-
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Objective: To investigate the mechanism of Farfarae Flos (FF) in Qingfei Paidu Decoction against coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking. Methods: Based on our previous study, the main compounds in FF were selected. The potential targets of FF were searched by Swiss Target Prediction and BATMAN-TCM database. GenCLiP 3 and GeneCard were used to predict and screen the therapeutic targets of COVID-19, and then Cytoscape 3.7.1 was used to build the compound-target-disease network. The String database was used to build the target PPI network. Gene ontology (GO) function enrichment analysis and KEGG pathway enrichment analysis were performed in the DAVID database. Molecular docking was performed based on the above compounds and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL hydrolase and angiotensin converting enzyme II (ACE2). Results: The compound-target-disease network contained 14 compounds, 104 targets and four diseases. GO function enrichment analysis revealed 444 GO items (P < 0.05), including 325 biological process (BP) items, 44 cell composition (CC) items and 75 molecular function (MF) items. A total of 94 signal pathways (P < 0.05) were screened out by KEGG pathway enrichment analysis. The results of molecular docking showed that the affinity of 3,4-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid with proteins were better than Remdesivir. Conclusion: The compounds in FF can bind with SARS-CoV-2 3CL hydrolase and ACE2, and then act on many targets to regulate multiple signaling pathways, thus exerting the therapeutic effect on COVID-19.
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OBJECTIVE@#This study aimed to investigate the molecular mechanism of RAB1A in the proliferation, invasion, and metastasis of human tongue squamous cell carcinoma.@*METHODS@#Western blot was used to detect the expression of RAB1A protein in human normal tongue epithelial cells (Hacat) and tongue squamous cell carcinoma Tca8113. The changes in RAB1A after plasmid transfection were also studied. The Tca8113 cells were named SiRAB1A/Tca8113 after RAB1A plasmid transfection. The expression of the epithelial-mesenchymal transition (EMT)-related markers of SiRAB1A/Tca8113 cells was also detected. CCK-8 assay was used to detect the proliferation of SiRAB1A/Tca8113 cells. Transwell and wound healing assays were used to detect the invasive and metastatic abilities of SiRAB1A/Tca8113 cells, respectively.@*RESULTS@#Western blot results showed that the expression of RAB1A in tongue squamous cell carcinoma cells was significantly higher than that in Hacat. RAB1A decreased significantly after SiRAB1A plasmid transfection. CCK-8 proliferation assay showed that the proliferation of SiRAB1A/Tca8113 cells also decreased significantly. Transwell and wound healing assays demonstrated that the invasive and metastatic abilities of SiRAB1A/Tca8113 cells decreased significantly, respectively. In addition, Western blot results demonstrated that RAB1A deletion significantly increased the expression of E-cadherin and inhibited the expression of Vimentin.@*CONCLUSIONS@#RAB1A could promote the proliferation, invasion, and metastasis of tongue squamous cell carcinoma cells.
Subject(s)
Humans , Carcinoma, Squamous Cell , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Head and Neck Neoplasms , Tongue NeoplasmsABSTRACT
OBJECTIVE： To study the imp rovement effects of Ganoderma lucidum polysaccharides crude extract on estradiol-induced thymus atrophy in mice. METHODS ：Totally 60 female ICR mice were randomly divided into normal control group（normal saline ），model group （normal saline ），G. lucidum polysaccharides crude extract high-dose and low-dose groups （400，100 mg/kg，by crude drug ），with 15 mice in each group. Except for normal control group ，other groups were given estradiol intraperitoneally （0.1 mg/mice，6 times）every other day to establish thymic atrophy model. The next day after modeling finished，they were given relevant medicine intragastrically ，once a day ，for consecutive 14 d. Twenty-four hours after last medication，organ（thymus，spleen）index，MDA content and GST activity in plasma were determined. HE staining was adopted to observe the pathological changes of thymus and spleen tissue in mice. The thymus cell apoptosis was examined by TUNEL assay ， and the T cell subsets in peripheral blood were detected by flow cytometry. RESULTS ：Compared with normal control group ，the thymus index ，proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were decreased significantly in model group （P＜0.01）；spleen index ，MDA content in plasma and thymocyte apoptosis level as well as the proportion of CD 3+CD8+T cell in peripheral blood were all increased significantly （P＜0.05 or P＜0.01）. Thymic cortex and medullary boundary of mice was blurred；the intercellular space was enlarged ；some cells were damaged and apoptotic in cortex ；no pathological changes were found in the spleen. Compared with model group ，thymus index and GST activity in plasma as well as proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were all increased significantly in G. lucidum polysaccharides crude extract high-dose group（P＜0.05 or P＜0.01）；while MDA content in plasma ，the apoptosis level of thymocytes were all decreased significantly （P＜0.01 or P＜0.05）；and the pathological changes of thymus were improved significantly. MDA content in plasma was decreased significantly in G. lucidum polysaccharides crude extract low-dose group （P＜0.01），and other indexes/pathological changes were not obvious. CONCLUSIONS ：High dose （400 mg/kg）of G. lucidum polysaccharides crude extract can improve the thymus atrophy induced by estradiol in mice.
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Objective:To investigate the risk factors of Crohn′s disease (CD)-related gastrointestinal stenosis, and to summarize and analyze the corresponding treatments.Methods:From January 2010 to December 2018, 122 patients diagnosed with CD and hospitalized in the Seventh Medical Center, PLA General Hospital were selected including 72 patients in gastrointestinal stenosis group and 50 patients in non-gastrointestinal stenosis group. The gender, age of onset, course of disease, location of lesions involved (Montreal classification), disease activity, extraintestinal manifestations, application of therapeutic drugs, and complications were compared between the two groups. The treatment of CD patients with gastrointestinal stenosis was analyzed. Multivariate logistic regression was used to analyze the risk factors of CD patients with gastrointestinal stenosis. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The age of onset of patients in gastrointestinal stenosis group was older than that in non-gastrointestinal stenosis group ((37.6±15.1) years old vs. (30.8±14.7) years old), and course of disease was longer than that of non-gastrointestinal stenosis group (72 months, 11 to 492 months vs. 45 months, 3 to 240 months); and the differences were statistically significant ( t=-2.044, Z=-2.770; P=0.018, 0.006). The proportion of patients with ileum involvement of the gastrointestinal stenosis group was lower than that of the non-gastrointestinal stenosis group (69.4%, 50/72 vs. 86.0%, 43/50), and the proportion of severe patients was higher than that of the non-gastrointestinal stenosis group (15.3%, 11/72 vs. 4.0%, 2/50); and the differences were statistically significant ( χ2=4.463 and 3.942, P=0.035 and 0.047). There were no significant differences in gender, use of therapeutic drugs, extraintestinal manifestations, application of therapeutic drugs or the incidence of complications between the patients of two groups (all P>0.05). The results of multivariate logistic regression showed that the age of onset and course of disease were risk factors of CD-related gastrointestinal stenosis ( β=0.028, odds ratio ( OR)=1.028, 95% confidence interval ( CI) 1.000 to 1.056, P=0.046; β=0.008, OR=1.008, 95% CI 1.002 to 1.015, P=0.013). Further stratified analysis revealed that the incidence rates of CD-related gastrointestinal stenosis in patients with age of onset over 40 years old and course of disease more than five years were higher than those of patients with age of onset less than 40 years old and course of disease less than five years (76.3%, 29/38 vs. 51.2%, 43/84; 68.4%, 39/57 vs. 50.8%, 33/65), and the differences were statistically significant ( OR=3.072, 95% CI 1.298 to 7.272, P=0.009; OR=2.101, 95% CI 1.002 to 4.406, P=0.048). Among the 72 CD patients with gastrointestinal stenosis, 15 cases (20.8%) were treated with medicine and nutrition, without endoscopic or surgical treatment. Fifty-two patients (72.2%) underwent surgical treatment, among them six patients (11.5%) received twice surgery, the interval between the two operations was 46 months (1 to 204 months), and eight patients (15.4%) had postoperative complications. Twenty-one patients (29.2%) were treated with endoscopic dilatation, and no complications occurred after surgery. Five patients (23.8%) underwent surgical treatment during the follow-up period. Conclusions:The age of onset over 40 years old and the course of disease more than five years are the risk factors of CD-related gastrointestinal stenosis. Individualized medical treatment is the basis for the treatment of CD-related gastrointestinal stenosis. Surgery is still the main treatment. The endoscopic treatment is safety and can delay or avoid surgery to a certain extent.
ABSTRACT
Objective: To compare the prognosis of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) stenosis. Methods: This was a retrospective study. Patients with symptomatic severe aortic stenosis, who underwent TAVR with follow-up time more than one year in Guangdong Provincial People's Hospital from April 2016 to August 2018, were included. According to aortic CT angiography, the patients were divided into BAV group and TAV group. The primary endpoint was the composite event of all-cause death and stroke, and the secondary endpoints were TAVR-related complications. Incidence of clinical endpoints and parameters derived from echocardiography were compared between the groups, and Kaplan-Meier survival analysis was used to compare the composite event between the two groups. Results: A total of 49 patients were included. The age was (73.6±6.3) years, and 25(51.0%) were male. There were 32 patients in BAV group and 17 in TAV group, the follow-up time was 466 (390, 664) days. The incidence of composite endpoint of death and stroke at one year were comparable in BAV and TAV groups (6.3% (2/32) vs. 5.9% (1/17), P=1.00). Kaplan-Meier curves also showed a similar risk of the composite endpoint(HR=1.03，95%CI 0.09-11.24，Log-rank P=0.98) between two groups. The incidence of all-cause death, stroke, myocardial infarction, severe bleeding, major vascular complications, new-onset atrial fibrillation or atrial flutter, and permanent pacemaker implantation were all similar between the two groups(all P>0.05), and there was no acute kidney injury (stage 2 or 3) in both groups. Echocardiographic parameters at one year were similar between the two groups (all P>0.05). Conclusions: The midterm prognosis of TAVR in patients with BAV and TAV stenosis is similar. Clinical trials of large sample size with long-term follow-up are warranted to verify our findings.