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Objective Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and network pharmacology technology combined with pharmacodynamic experiments were used to analyze the quality markers(Q-markers)in Saorilao Qingfei Zhike Capsules.Methods Using UPLC-Q-TOF-MS technology,the chemical components in different polar extracts of Saorilao Qingfei Zhike Capsules was analyzed.Potential pharmacological components were screened by using antitussive and expectorant models.The"components-targets-diseases"network was constructed and potential Q-markers were screened by network pharmacology technology.Then we conducted pharmacodynamic validation to confirm the Q-markers,which have antitussive and expectorant effects in Saorilao Qingfei Zhike Capsules.Results A total of 120 compounds were obtained from the Saorilao Qingfei Zhike Capsules through qualitative analysis.Among the extracts of different polarity,44 compounds were derived from petroleum ether extract,85 compounds were derived from ethyl acetate extract,79 compounds were derived from n-butanol extract,and 71 compounds were derived from water extract.The results of pharmacological experiments showed that among extracts of different polarity,petroleum ether extract had the best antitussive effect,while n-butanol extract had the best expectorant effect.Three core components for eliminating phlegm and relieving cough were screened through network pharmacology techniques:farcalinol,farcalinediol,and rubimaillin.Pharmacodynamic studies verified that all core components mentioned above have certain antitussive and expectorant effects.Conclusion Based on the above research,farcalinol,farcalindiol,and rubimaillin can be used as Q-markers for the antitussive and expectorant effects of Saorilao Qingfei Zhike Capsules.This paper provides reference for the quality standard of Saorilao Qingfei Zhike Capsules.
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@#Abstract: KRAS protein, a small GTPase encoded by the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene, is involved in cell proliferation, differentiation, migration and cell survival, and is known as a regulatory switch for the cell life cycle. However, KRAS gene is prone to mutation, leading to hyperactivation of its downstream signaling pathways, and has a vital role in driving tumorigenesis. KRAS mutations predominantly take place at residue G12, G13 or Q61, and different mutants have varying effects on protein physiological functions and tumor types. Due to its smooth surface and high affinity for nucleotides, KRAS had been considered to be “undruggable” until the launch of selective KRAS G12C inhibitors sotorasib and adagrasib, which broke the dogma. This review introduces the structure and functions of KRAS, as well as the status and progress of inhibitors directly targeting KRAS mutants (G12C, G12D, G12R, G12S) and pan-KRAS inhibitors, aiming to provide some insightful reference for the development of KRAS inhibitors.
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Objectives@#. The necessity to develop a method for prognostication and to identify novel biomarkers for personalized medicine in patients with head and neck squamous cell carcinoma (HNSCC) cannot be overstated. Recently, pathomics, which relies on quantitative analysis of medical imaging, has come to the forefront. CXCL8, an essential inflammatory cytokine, has been shown to correlate with overall survival (OS). This study examined the relationship between CXCL8 mRNA expression and pathomics features and aimed to explore the biological underpinnings of CXCL8. @*Methods@#. Clinical information and transcripts per million mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA)-HNSCC dataset. We identified correlations between CXCL8 mRNA expression and patient survival rates using a Kaplan-Meier survival curve. A retrospective analysis of 313 samples diagnosed with HNSCC in the TCGA database was conducted. Pathomics features were extracted from hematoxylin and eosin–stained images, and then the minimum redundancy maximum relevance, with recursive feature elimination (mRMR-RFE) method was applied, followed by screening with the logistic regression algorithm. @*Results@#. Kaplan-Meier curves indicated that high expression of CXCL8 was significantly associated with decreased OS. The logistic regression pathomics model incorporated 16 radiomics features identified by the mRMR-RFE method in the training set and demonstrated strong performance in the testing set. Calibration plots showed that the probability of high gene expression predicted by the pathomics model was in good agreement with actual observations, suggesting the model’s high clinical applicability. @*Conclusion@#. The pathomics model of CXCL8 mRNA expression serves as an effective tool for predicting prognosis in patients with HNSCC and can aid in clinical decision-making. Elevated levels of CXCL8 expression may lead to reduced DNA damage and are associated with a pro-inflammatory tumor microenvironment, offering a potential therapeutic target.
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ObjectiveTo examine the inhibitory effects of berberine compounds, including columbamine, on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier (BBB) permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration (IC50) of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters (Koff) of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds (including medicinal herbs and compound formulas) was conducted using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). ResultBerberine compounds, including columbamine, exhibited strong inhibition of acetylcholinesterase, with IC50 values in the nanomolar range. Moreover, they displayed better drug-target binding kinetics characteristics (with smaller Koff values) than the positive control of donepezil hydrochloride (P<0.01), indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer, as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance, this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease, providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.
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ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus(SCF) based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism, intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration, and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC Q-Exactive Orbitrap MS) was used to analyze and compare the differences in the spectra of SCF extract, blank plasma, administered plasma, blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column(2.1 mm×100 mm, 1.7 µm), the mobile phase was acetonitrile(A)-0.1% formic acid aqueous solution(B) for gradient elution(0-7 min, 95%B; 7-12 min, 95%-35%B; 12-17 min, 35%-15%B; 17-20 min, 15%-12%B; 20-22 min, 12%-5%B; 22-23 min, 5%B; 23-25 min, 5%-95%B; 25-28 min, 95%B). And heated electrospray ionization(HESI) was used with positive and negative ion modes, the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time, characteristic fragments, molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF, including lignans, flavonoids, amino acids, tannins, and others, of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation, methylation, demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats, it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.
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ObjectiveTo study the metabolism of chemical components from Citri Reticulatae Pericarpium(CRP)in different parts of rats by sequential metabolism and ultra performance liquid chromatography-high resolution mass spectrometry(UPLC-HRMS). MethodSD male rats were employed as experimental subjects, and blood samples of intestinal metabolism and hepatic metabolism were prepared after administration of CRP ethanol extract by in situ intestinal perfusion, and comprehensive metabolic samples were collected after intragastric administration. UPLC-HRMS was used to analyze the samples with acetonitrile(A)-0.1% formic acid aqueous solution(B)as the mobile phase for gradient elution(0-10 min, 10%-30%A; 10-30 min, 30%-95%A; 30-31 min, 95%-10%A; 31-35 min, 10%A)at a flow rate of 0.35 mL·min-1, using a heated electrospray ionization with positive and negative ion mode scanning in the range of m/z 100-1 500. Under these conditions, the differences in the profiles of CRP ethanol extract, blank plasma and drug-containing plasma under different treatment groups were compared, and the chemical components of each sample were analyzed and identified based on the retention time, accurate relative molecular mass, primary and secondary ion fragments, and the information of reference substances. ResultA total of 44 chemical components were identified in the CRP ethanol extract, including flavone-O-glycosides, flavone-C-glycosides and polymethoxyflavonoids, etc. The results of sequential metabolism showed that 22 chemical components in CRP were detected in the intestinal metabolic sample, 18 chemical components were detected in the hepatic metabolic sample, and 9 identical chemical components(narirutin, hesperidin, meranzin, 5,7,8,3ʹ,4ʹ,5ʹ-hexamethoxy-flavone, isosinensetin, sinensetin, 3,5,6,7,8,3ʹ,4ʹ-heptamethoxyflavone, nobiletin and tangeretin)could be detected in all three metabolic samples, with a total of 22 compounds entering the blood in prototype form. ConclusionThe identified 21 components with well-defined structures entering the blood as prototypes may be potential active components of CRP, and differences in the components at different metabolic parts can provide an experimental basis for elucidating the in vivo biotransformation process of the metabolic components of CRP.
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Constructing photocatalyst with both high efficiency and selectivity is highly desired in water treatment process. However, it is difficult to realize the selectivity of photocatalysis due to the non-selective oxidative species produced in this process. Herein, for the first time, the photocatalytic selectivity was achieved on g-C3N4 (CN) through N vacancy introduction for effective removal of organic pollutants, and the mechanism of vacancy induced selectivity enhancement was studied. The nitrogen vacancy modified CN (VCN) showed enhanced photocatalytic activity and unique selectivity towards phenolic compounds with electron-donating group, whose kinetic constant for p-aminophenol (p-NH2) degradation was 5.95 times higher than that over CN. Moreover, VCN photocatalytic system also displayed similar selectivity in binary pollutant systems. Characteristics and theoretical calculation results confirmed the enhanced photocatalytic performance and selectivity of VCN was mainly attributed to the effect of N vacancy. On one hand, electron-deficient N vacancy enhanced the adsorption of the O2 and phenolic compounds, which promoted the production of O2â¢- and strengthened the photocatalytic surface reaction. On the other hand, the N vacancy preferred to adsorb the electron-donating groups of phenolic compounds, which resulted in their selective removal.
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Nitrogen , Water Purification , Catalysis , Light , Phenols , Water Purification/methodsABSTRACT
To explore pharyngeal sensory function by current perception threshold (CPT) measurement in paresthetic pharynx. In total, 58 healthy participants and 66 patients with pharyngeal paresthetic symptoms underwent CPT evaluation. Pharyngeal paresthesia (n = 66) was classified into three categories based on aetiologies: six cases with pain in pharynx; 34 neuropathic patients with glossopharyngeal nerve and/or vagus nerve or recurrent laryngeal nerve injury; and 26 patients with globus pharyngeus. CPT measurements were obtained from bilateral palatoglossal arch and tongue base at 2000, 250 and 5 Hz stimulation frequencies. Ranked from high to low, the CPT values for the bilateral palatoglossal arches and tongue bases were: lower cranial neuropathic patients, globus pharyngeus, healthy participants and patients with pain. The CPT values for neuropathic patients on the injured side were significantly higher than those on the healthy side (P < 0.05). The CPT values for patients with pain in pharynx were significantly lower than those of healthy participants (P < 0.05) when the bilateral tongue bases were stimulated. The CPT measurement is a reliable method for quantitatively assessing pharyngeal sensory function and able to differentiate pharyngeal paresthesia between lower cranial neuropathic and subjective discomfort. Pharyngeal sensory function is more sensitive in patients with pain in pharynx. Pharyngeal sensory function is significantly reduced in lower cranial neuropathic patients, especially on the injured side. Patients with globus pharyngeus have pharyngeal hyposensitivity.
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Paresthesia , Pharynx , Humans , Paresthesia/etiology , Pharynx/innervation , Sensation , Perception , PainABSTRACT
Confusional arousal (CA) is a rare non-rapid eye movement sleep-related parasomnia and rarely reported in China, leading to misdiagnosis and mistreatment in clinic. A detailed collection of clinical symptoms and simultaneous video polysomnography is very important for diagnosis and differential diagnosis of CA. A elderly patient with CA was diagnosed according to the International classification of sleep disorders, third edition diagnostic criteria. The summary and analysis of the patient is conducted to improve the understanding of CA, meanwhile to avoid misdiagnosis and mistreatment.
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Objective:To investigate the clinical efficacy of azithromycin combined with methylprednisolone in the treatment of severe mycoplasma pneumonia in children.Methods:A total of 200 children patients with severe mycoplasma pneumonia who received treatment in Putuo District People's Hospital of Zhoushan, China from January 2015 to December 2018 were included in this study. They were randomly assigned to receive treatment with azithromycin (control group, n = 100) or azithromycin combined with methylprednisolone (observation group, n = 100) for 7 successive days. Time to improvement of signs and symptoms, total effective rate, inflammatory factors, incidence of adverse reactions, and length of hospital stay were compared between the control and observation groups. Results:Fever subsidence time, cough disappearance time, lung rale disappearance time and length of hospital stay in the observation group were (6.30 ± 2.16) d, (10.05 ± 2.36) d, (7.06 ± 1.95) d, (11.06 ± 2.07) d, which were significantly shorter than those in the control group [(7.75 ± 2.84) d, (12.37 ± 3.10) d, (12.30 ± 2.2) d, (14.78 ± 2.61) d, t = 4.064, 5.955, 17.734, 11.167, all P < 0.05). Total effective rate in the observation group was significantly higher than that in the control group [97.0% (97/100) vs. 85.0% (85/100), χ2 = 8.791, P < 0.05]. After treatment, C-reactive protein, interleukin-6, interleukin-10 and tumor necrosis factor levels in the observation group were (8.72 ± 2.19) mg/L, (13.50 ± 3.65) ng/L, (6.06 ± 1.25) ng/L, (16.28 ± 5.09) ng/L, which were significantly lower than those in the control group [(16.11 ± 3.73) mg/L, (25.13 ± 4.86) ng/L, (8.42 ± 1.74) ng/L, (36.20 ± 6.41) ng/L, t = 17.085, 19.135, 11.015, 24.337, all P < 0.05]. There was no significant difference in the incidence of adverse reactions between the observation and control groups ( P > 0.05). Conclusion:Azithromycin combined with methylprednisolone is highly effective and safe for the treatment of severe mycoplasma pneumonia in children. This treatment method can improve clinical symptoms and reduce inflammatory reactions in children with severe mycoplasma pneumonia.
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Objective:To explore the clinical significance of different metabolic parameters measured by 18F-fluorodeoxyglucose (FDG) PET/CT in predicting the effectiveness of chemotherapy in advanced lung adenocarcinoma patients. Methods:A set of metabolic parameters of PET/CT and clinical characteristics which were detected from 127 patients (70 males, 57 females, age (56.8±10.1) years) with advanced lung adenocarcinoma treated with at least two cycles of chemotherapy in Hainan Cancer Hospital between August 2017 and June 2019 were retrospectively analyzed. The effects of those parameters on patients′ survival were analyzed by receiver operating characteristic (ROC) curve, Kaplan-Meier method (log-rank test) and Cox proportional hazards model.Results:Maximum standardized uptake value (SUV max), metabolic tumor volume 30% (MTV 30), and total lesion glycolysis 30% (TLG 30) had larger areas under the curve (0.581, 0.606 and 0.693 respectively) compared with other imaging parameters, and the optimal cut-off values were 10.12, 20.21 cm 3 and 81.25 g respectively. Kaplan-Meier univariate and Cox analyses synergistically showed that clinical stage (hazard ratio ( HR)=0.293(95% CI: 0.190-0.451), P<0.001), smoking ( HR=0.732(95% CI: 0.605-0.885), P=0.001), and MTV 30 ( HR=1.555(95% CI: 1.078-2.242), P=0.018) had significant predictive value for progression-free survival (PFS). Stratified analysis showed that smoking and MTV 30>20.21 cm 3 were independent prognostic factors for poor PFS in patients with advanced lung adenocarcinoma receiving chemotherapy ( HR=0.738(95% CI: 0.611-0.893), P=0.002; HR=1.502(95% CI: 1.037-2.177), P=0.032). Conclusions:Clinical stage, smoking and MTV 30 are independent prognostic factors of PFS in patients with advanced lung adenocarcinoma receiving chemotherapy. MTV 30≤20.21 cm 3 is expected to be an image biomarker for predicting survival and selecting patients with advanced lung adenocarcinoma who are more likely to benefit from chemotherapy.
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Myeloid-derived suppressor cells (MDSCs) are a group of immature bone marrow cells with an immunosuppressive effect, and they are abundant in tumor patients and can induce tumor cells to escape the killing of immune cells and thus promote the development, progression, and metastasis of tumor. In recent years, its role in hepatocellular carcinoma microenvironment has attracted more and more attention, but the mechanisms of its recruitment and differentiation in hepatocellular carcinoma microenvironment have not been clearly elucidated. This article mainly summarizes the mechanism of action of tumor cells and tumor stromal cells in hepatocellular carcinoma microenvironment (such as hepatic stellate cells, tumor-associated fibroblasts, and tumor-associated endothelial cells) in the recruitment and differentiation of MDSCs, and it is proposed to target MDSCs as an adjuvant therapy to enhance the potential value of immunotherapy for liver cancer.
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OBJECTIVE@#To investigate the accuracy of automatic segmentation of organs at risk (OARs) in radiotherapy for nasopharyngeal carcinoma (NPC).@*METHODS@#The CT image data of 147 NPC patients with manual segmentation of the OARs were randomized into the training set (115 cases), validation set (12 cases), and the test set (20 cases). An improved network based on three-dimensional (3D) Unet was established (named as AUnet) and its efficiency was improved through end-to-end training. Organ size was introduced as a priori knowledge to improve the performance of the model in convolution kernel size design, which enabled the network to better extract the features of different organs of different sizes. The adaptive histogram equalization algorithm was used to preprocess the input CT images to facilitate contour recognition. The similarity evaluation indexes, including Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD), were calculated to verify the validity of segmentation.@*RESULTS@#DSC and HD of the test dataset were 0.86±0.02 and 4.0±2.0 mm, respectively. No significant difference was found between the results of AUnet and manual segmentation of the OARs (@*CONCLUSIONS@#AUnet, an improved deep learning neural network, is capable of automatic segmentation of the OARs in radiotherapy for NPC based on CT images, and for most organs, the results are comparable to those of manual segmentation.
Subject(s)
Humans , Databases, Factual , Image Processing, Computer-Assisted , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/radiotherapy , Organs at Risk , Tomography, X-Ray ComputedABSTRACT
Objective@#To explore serum levels of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF), and whether changes of BDNF and GDNF are correlated with sleep quality and cognitive function in patients with chronic insomnia disorder (CID).@*Methods@#Fifty-seven CID patients in the Department of Sleep Disorders, Chaohu Hospital of Anhui Medical University and 30 healthy controls were enrolled from May 2017 to July 2018. Pittsburgh Sleep Quality Index (PSQI) was used to assess the degree of insomnia severity (some CID patients were monitored by overnight polysomnography). Montreal Cognitive Assessment (MoCA) scale and Nine-Box Maze were used to assess general cognitive function and specific memory function, respectively. The serum levels of BDNF and GDNF were detected using ELISA.@*Results@#Compared to the controls, CID patients had significantly higher PSQI scores (CID patients: 14.0±2.2, healthy controls: 3.9±1.1; t=28.093, P<0.01), lower MoCA scores (CID patients: 24.5±3.6, healthy controls: 26.5±0.9; t=-2.985, P<0.01), more errors in object working memory (CID patients: 1.0 (0, 1.0), healthy controls: 0 (0, 0.3)), spatial working memory (CID patients: 3.0 (2.0, 4.0), healthy controls: 1.0 (1.0, 2.0)) and object recognition memory (CID patients: 0 (0, 0), healthy controls: 0 (0, 0); Z=-2.896、-5.007、-2.306, P<0.05), and lower serum BDNF (CID patients: (19.48±7.50) ng/ml, healthy controls: (46.49±13.33) ng/ml; t=-10.274, P<0.01) and GDNF (CID patients: (32.76±14.04) pg/ml, healthy controls: (59.63±20.30) pg/ml; t=-7.240, P<0.01). The partial correlation analysis showed that in the CID patients, the levels of BDNF and GDNF were correlated with PSQI scores negatively (r=-0.293, -0.320, P<0.05) and MoCA scores positively (r=0.331, 0.295, P<0.05). The BDNF level was also correlated with the duration of disease and the errors in the spatial working memory test negatively (r=-0.319, -0.393, P<0.05), and the GDNF level was correlated with the total sleep time detected with polysomnogram positively (r=0.520, P<0.05).@*Conclusion@#Serum BDNF and GDNF levels in CID patients were lower than those in healthy controls, and correlated with sleep quality and cognitive impairment.
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Objective@#To explore serum levels of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF), and whether changes of BDNF and GDNF are correlated with sleep quality and cognitive function in patients with chronic insomnia disorder (CID).@*Methods@#Fifty-seven CID patients in the Department of Sleep Disorders, Chaohu Hospital of Anhui Medical University and 30 healthy controls were enrolled from May 2017 to July 2018. Pittsburgh Sleep Quality Index (PSQI) was used to assess the degree of insomnia severity (some CID patients were monitored by overnight polysomnography). Montreal Cognitive Assessment (MoCA) scale and Nine-Box Maze were used to assess general cognitive function and specific memory function, respectively. The serum levels of BDNF and GDNF were detected using ELISA.@*Results@#Compared to the controls, CID patients had significantly higher PSQI scores (CID patients: 14.0±2.2, healthy controls: 3.9±1.1; t=28.093, P<0.01), lower MoCA scores (CID patients: 24.5±3.6, healthy controls: 26.5±0.9; t=-2.985, P<0.01), more errors in object working memory (CID patients: 1.0 (0, 1.0), healthy controls: 0 (0, 0.3)), spatial working memory (CID patients: 3.0 (2.0, 4.0), healthy controls: 1.0 (1.0, 2.0)) and object recognition memory (CID patients: 0 (0, 0), healthy controls: 0 (0, 0); Z=-2.896、-5.007、-2.306, P<0.05), and lower serum BDNF (CID patients: (19.48±7.50) ng/ml, healthy controls: (46.49±13.33) ng/ml; t=-10.274, P<0.01) and GDNF (CID patients: (32.76±14.04) pg/ml, healthy controls: (59.63±20.30) pg/ml; t=-7.240, P<0.01). The partial correlation analysis showed that in the CID patients, the levels of BDNF and GDNF were correlated with PSQI scores negatively (r=-0.293, -0.320, P<0.05) and MoCA scores positively (r=0.331, 0.295, P<0.05). The BDNF level was also correlated with the duration of disease and the errors in the spatial working memory test negatively (r=-0.319, -0.393, P<0.05), and the GDNF level was correlated with the total sleep time detected with polysomnogram positively (r=0.520, P<0.05).@*Conclusion@#Serum BDNF and GDNF levels in CID patients were lower than those in healthy controls, and correlated with sleep quality and cognitive impairment.
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Objective@#By adopting network pharmacology to study the mechanism of the two classical Chinese herbs Danggui-Baishao in treating cardiovascular diseases.@*Methods@#By searching from TCMSP and related literature, together with the databases of TCMSP, SWISS and STITCH, potential active compounds of Danggui-Baishao were collected, while the targets for cardiovascular diseases were obtained from TTD, OMIM and DrugBank databases. Then the PPI network was screened for the major targets. The KEGG Pathway annotation analyses of major targets were performed by using the DAVID database. The ingredient-major target-key pathway network was constructed by Cytoscape.@*Results@#There were 17 compounds and 54 major targets in the ingredient-target-pathway network, as well as 10 key pathways, including inflammation-related pathway (TNF signaling pathway), pathways related to cardiovascular system (such as PI3K-Akt signaling pathway, FoxO signaling pathway, VEGF signaling pathway, Rap1 signaling pathway), prolactin signaling pathway and estrogen signaling pathway.@*Conclusions@#The study verified the characteristics of multi-components, multi-targets and integral regulation for Danggui-Baishao with the application of network pharmacology. It predicted that Dangui-Baishao couldtreat cardiovascular diseases mainly by regulating angiogenesis, inflammatory response and apoptosis.
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Objective:By adopting network pharmacology to study the mechanism of the two classical Chinese herbs Danggui-Baishao in treating cardiovascular diseases. Methods:By searching from TCMSP and related literature, together with the databases of TCMSP, SWISS and STITCH, potential active compounds of Danggui-Baishao were collected, while the targets for cardiovascular diseases were obtained from TTD, OMIM and DrugBank databases. Then the PPI network was screened for the major targets. The KEGG Pathway annotation analyses of major targets were performed by using the DAVID database. The ingredient-major target-key pathway network was constructed by Cytoscape. Results:There were 17 compounds and 54 major targets in the ingredient-target-pathway network, as well as 10 key pathways, including inflammation-related pathway (TNF signaling pathway), pathways related to cardiovascular system (such as PI3K-Akt signaling pathway, FoxO signaling pathway, VEGF signaling pathway, Rap1 signaling pathway), prolactin signaling pathway and estrogen signaling pathway.Conclusions:The study verified the characteristics of multi-components, multi-targets and integral regulation for Danggui-Baishao with the application of network pharmacology. It predicted that Dangui-Baishao couldtreat cardiovascular diseases mainly by regulating angiogenesis, inflammatory response and apoptosis.
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Objective To explore serum levels of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF),and whether changes of BDNF and GDNF are correlated with sleep quality and cognitive function in patients with chronic insomnia disorder (CID).Methods Fifty-seven CID patients in the Department of Sleep Disorders,Chaohu Hospital of Anhui Medical University and 30 healthy controls were enrolled from May 2017 to July 2018.Pittsburgh Sleep Quality Index (PSQI) was used to assess the degree of insomnia severity (some CID patients were monitored by overnight polysomnography).Montreal Cognitive Assessment (MoCA) scale and Nine-Box Maze were used to assess general cognitive function and specific memory function,respectively.The serum levels of BDNF and GDNF were detected using ELISA.Results Compared to the controls,CID patients had significantly higher PSQI scores (CID patients:14.0±2.2,healthy controls:3.9± 1.1;t=28.093,P<0.01),lower MoCA scores (CID patients:24.5±3.6,healthy controls:26.5±0.9;t=-2.985,P<0.01),more errors in object working memory(CID patients:1.0 (0,1.0),healthy controls:0 (0,0.3)),spatial working memory (CID patients:3.0 (2.0,4.0),healthy controls:1.0 (1.0,2.0)) and object recognition memory (CID patients:0 (0,0),healthy controls:0 (0,0);Z=-2.896、-5.007、-2.306,P<0.05),and lower serum BDNF (CID patients:(19.48 ± 7.50) ng/ml,healthy controls:(46.49± 13.33) ng/ml;t=-10.274,P<0.01) and GDNF (CID patients:(32.76± 14.04) pg/ml,healthy controls:(59.63±20.30) pg/ml;t=-7.240,P<0.01).The partial correlation analysis showed that in the CID patients,the levels of BDNF and GDNF were correlated with PSQI scores negatively (r=-0.293,-0.320,P<0.05) and MoCA scores positively (r=0.331,0.295,P<0.05).The BDNF level was also correlated with the duration of disease and the errors in the spatial working memory test negatively (r=-0.319,-0.393,P<0.05),and the GDNF level was correlated with the total sleep time detected with polysomnogram positively (r=0.520,P<0.05).Conclusion Serum BDNF and GDNF levels in CID patients were lower than those in healthy controls,and correlated with sleep quality and cognitive impairment.
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Objective:To explore the changes of serum levels of copeptin and α-amylase and their correlations with sleep and cognition in patients with chronic insomnia (CI).Methods:From September 1, 2018 to May 31, 2019, fifty CI outpatients or inpatients from the Department of Sleep Disorder, Affiliated Chaohu Hospital of Anhui Medical University, were enrolled continuously, and thirty good sleepers from the Physical Examination Center of the hospital, were also enrolled to serve as controls. Pittsburgh Sleep Quality Index (PSQI), polysomnography (PSG) and Pre-Sleep Arousal Scale (PSAS) were used to assess the insomnia severity and sleep disorder susceptibility. Montreal Cognitive Assessment scale (MoCA) and Nine-Box Maze were used to respectively assess general cognition and memories. The serum levels of copeptin and α-amylase were detected using enzyme linked immunosorbent assay.Results:Compared to the controls, the CI patients had increased PSQI score (16.0 (15.0, 17.0) vs 4.0 (2.8, 6.0); Z=-7.678, P<0.001) and PSAS score (33.0 (30.0, 37.5) vs 17.0 (16.0, 18.5); Z=-7.350, P<0.001), decreased MoCA score (24.1±2.5 vs 26.7±1.9, t=-4.625, P<0.001), increased numbers of errors in the object working (1.0 (0, 1.0) vs 0 (0, 1.0), Z=-2.099, P=0.036), spatial working (2.0 (1.0, 4.0) vs 1.0 (0, 2.0), Z=-3.935, P<0.001) and object recognition (1.0 (0, 2.0) vs 0 (0, 0), Z=-2.266, P=0.023) memories, and elevated serum levels of copeptin ((35.1±19.9) pg/ml vs (14.8±6.9) pg/ml, t=5.414, P<0.001) and α-amylase ((990.1±193.7) U/L vs (728.9±230.5) U/L, t=5.597, P<0.001). In the CI patients, the level of copeptin was positively correlated with PSQI score ( r=0.338, P=0.013), PSAS score ( r=0.316, P=0.021), sleep latency ( r=0.324, P=0.018), number of awake ( r=0.325, P=0.017) and stage 1 percent of non-rapid eye movement sleep ( r=0.278, P=0.044), and negatively correlated with stage 2 percent of non-rapid eye movement sleep ( r=-0.279, P=0.043); α-amylase was positively correlated with numbers of awake in PSG ( r=0.293, P=0.033). Multiple linear regression analysis showed that copeptin level affected PSQI score (β=0.255, P=0.043) and sleep latency (β=0.254, P=0.043). Conclusion:The levels of copeptin and α-amylase in CI patients elevate, and copeptin may be associated with initial sleep difficulties, but not with cognitive ability, in patients with CI.
ABSTRACT
OBJECTIVE: To establish a method for simultaneous determination of isoquercitrin, astragalin and salvianolic acid B in Moringa oleifera leaves granules. METHODS: HPLC method was adopted. The determination was performed on Cosmosil-C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution (gradient elution) at flow rate of 1.3 mL/min. The column temperature was 40 ℃ and detection wavelength was set at 260 nm. The sample size was 10 μL. RESULTS: The linear ranges of isoquercitrin, astragalin and salvianolic acid B were 0.017-0.341, 0.010-0.194, 0.010-0.195 mg/mL, respectively (all r>0.999 0). The detection limits were 0.085, 0.143, 0.117 μg/mL, and the limits of quantitation were 0.283, 0.476, 0.392 μg/mL, respectively. RSDs of precision, stability (24 h) and reproducibility tests were all lower than 2.0% (n=6). Average recoveries were 101.22%, 98.76% and 98.72%, and RSDs were 0.66%,0.30%,0.30% (n=6), respectively. CONCLUSIONS: The established method is simple, accurate and reproducible. It can be used for simultaneous determination of isoquercitrin, astragalin and salvianolic acid B in M. oleifera leaves granules.