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AIM: To analyze the chemical ingredients of Qingxin-zishen prescription decoction (QZPD) and predict its main pharmacodynamic substances and mechanism in the prevention and treatment of menopause syndrome (MPS) with the help of high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS) combined with network pharmacology. METHODS: The chemical ingredients of QZPD were identified after analyzing the retention time, exact mass, secondary mass spectrometry fragmentation and other information obtained from HPLC-Q-TOF/MS and comparing them with the established chemical ingredients database and the literatures. The targets of ingredients in QZPD were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction database. The disease targets of MPS were obtained through Online Mendelian Inheritance in Man (OMIM) and GeneCards Database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of potential targets were analyzed with the Metascape database. Cytoscape 3.7.2 software was used to construct the network of active components-key targets-pathways. AutoDockTools 4.2.5 software was applied in the molecular docking verification between the key active components and key targets. RESULTS: A total of 83 components were identified in QZPD and 847 drug targets were predicted. After intersection them with 3 050 disease targets, 395 common targets were obtained. After network topology analysis, 74 key targets were obtained, involving mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), transforming growth factor-β (TGF-β) and other signaling pathways. Molecular docking analysis results indicated that 23 key active components, such as berberine, epiberberine, coptisine, geissoschizine methyl ether, liensinine, norcoclaurine, palmatine, quercetin, and luteolin, had good binding activity with several of the key targets. CONCLUSION: This study preliminarily identifies the potential effective chemical ingredients of QZPD, predicts its targets in the prevention and treatment of MPS, which provides supporting information for the further study of the pharmacodynamic substances and mechanisms of QZPD.
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The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to more than 100 countries posing as a serious threat to the public health on a global scale. Patients with comorbidity such as hypertension suffer more severe infection with elevated case fatality rate. Development of effective anti-viral drug is in urgent need to treat COVID-19 patients. Here we report that calcium channel blockers (CCBs), a type of anti-hypertension drugs that are widely used in the clinics, can significantly inhibit the post-entry replication events of SARS-CoV-2 in vitro. Comparison with two other major types of anti-hypertension drugs, the angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), showed that only CCBs display significant anti-SARS-CoV-2 efficacy. Combined treatment with chloroquine and CCBs significantly enhanced the anti-SARS-CoV-2 efficacy. Retrospective clinical investigation of COVID-19 patients revealed that the CCB amlodipine besylate administration was associated with reduced case fatality rate of patients with hypertension. Results from this study suggest that CCB administration for COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.
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BackgroundData regarding critical care for patients with severe COVID-19 are limited. We aimed to describe the clinical course, multi-strategy management, and respiratory support usage for the severe COVID-19 at the provincial level. MethodsUsing data from Sichuan Provincial Department of Health and the multicentre cohort study, all microbiologically confirmed COVID-19 patients in Sichuan who met the national severe criteria were included and followed-up from the day of inclusion (D1), until discharge, death, or the end of the study. FindingsOut of 539 COVID-19 patients, 81 severe cases (15.0%) were identified. The median (IQR) age was 50 (39-65) years, 37% were female, and 53.1% had chronic comorbidities. All severe cases were identified before requiring mechanical ventilation and treated in the intensive care units (ICUs), among whom 51 (63.0%) were treated in provisional ICUs and 77 patients (95.1%) were admitted by D1. On D1, 76 (93.8%) were administered by respiratory support, including 55 (67.9%) by conventional oxygen therapy (COT), 8 (9.9%) by high-flow nasal cannula (HFNC) and 13 (16.0%) by non-invasive ventilation (NIV). By D28, 53 (65.4%) were discharged, three (3.7%) were deceased, and 25 (30.9%) were still hospitalized. COT, administered to 95.1% of the patients, was the most commonly used respiratory support and met 62.7% of the respiratory support needed, followed by HFNC (19.3%), NIV ventilation (9.4%) and IV 8.5%. InterpretationThe multi-strategy management for severe COVID-19 patients including early identification and timely critical care may contribute to the low case-fatailty. Preparation of sufficient conventional oxygen equipment should be prioritized. Trial registration numberChiCTR2000029758.
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Objective To observe the T cells immune response to Enolase (Eno),an immunodominant antigen of Candida albicans.Methods Determined the frequencies of positive spot-forming cells (SFCs) of Eno antigen-specific T cells secreting IFN-γ,IL-4 and IL-17A in the PBMCs of 25 healthy individuals by ELISPOT assay.Results After Eno stimulation,the SFCs of IFN-γ,IL-4 and IL 17A in 25 healthy persons were 14.00(8.50,39.00),0(0,0) and 2(1,4.50),respectively.Either the SFCs of IFN-γ or those of IL-17A were significantly higher than those of IL-4 (P＜0.05).The difference between SFCs of IFN-γ and those of IL-17A was also significant (P=0).The response rates of IFN-γ,IL-4 and IL-17A were 100％ (25/25),4.00％ (1/25) and 88.00％ (22/25),respectively.The difference between either IFN-γor IL 17A and IL-4 was significant (values all P＜0.05).Eno induced strong response (SCFs≥20) for IFN-γ in 10 healthy individuals (40.00％,10/25),but failed to induce strong response for IL-17A and IL-4 in all the volunteers.Major healthy individuals (84.00％,21/25)showed both Th1 and Th17 cells response against Eno,12.00％ (3/25) showing Th1 cells response in isolation,and none showed Th2 or Th17 cells response individually.Conclusion Eno of Candida albicans could induce immunodominant responses of Th1 and Th17 cells,which was considered to provide protection to IC.Eno might be a potential protective vaccine against IC.
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To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.
Subject(s)
Humans , Antioxidants , Chemistry , Apoptosis , Hep G2 Cells , Nitrates , Chemistry , Pharmacology , Nitric Oxide , Metabolism , Nitric Oxide Donors , Chemistry , Oleanolic Acid , Chemistry , Pharmacology , Structure-Activity Relationship , Ursodeoxycholic Acid , PharmacologyABSTRACT
To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.
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OBJECTIVE@#To explore the criminological characteristics of mental retardation (MR) in forensic psychiatry.@*METHODS@#The record scale of forensic psychiatric assessment designed by ourselves was used to analyse the criminological characteristics of 83 offenders with MR, and to compare the criminological characteristics of mild MR with that of moderate and severe MR.@*RESULTS@#The mild MR accounted for 62.7%, moderate and severe MR was 22.9%. The percentage of sex offenders in MR was 37.3%, manslaughter 34.7%, property offences 28.0%, respectively. Additionally, 96.1% cases with MR have definite criminal motives, and the criminal history was established in 34.7% cases. Significant differences of criminal premeditation (X2chi-squared l11,P=0.001), criminal aim(x2chi-squared 7.531, P=0.006), criminal motive(X 2chi-squared . 920, P= 0.019) and criminal types(s 2chi-squared .855, P=0.02) were found between the mild MR and the moderate, severe MR.@*CONCLUSIONS@#The criminal offenders were mostly found in mild MR. The sex offenders and manslaughter were in outright majority, and most of them had definite criminal motives. The proportion of offenders in mild MR who had criminal premeditation and criminal aim was higher significantly than which in the moderate, severe MR. The proportion of offenders in moderate, severe MR whose criminal motive was for sex was higher than that in mild MR.
