Network pharmacology and molecular docking reveal the mechanism of resveratrol in oral squamous cell carcinoma treatment / 口腔疾病防治

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

Caries prevention mechanism of the Xinjiang Mori Cortex based on network pharmacology and its effect on the main cariogenic bacteria / 口腔疾病防治

Objective@#To investigate the potential caries prevention mechanism of the Xinjiang Mori cortex and to analyze its effect on the main cariogenic bacteria.@*Methods@#The active components of the Xinjiang Mori cortex and the main targets were predicted and screened using the TCMSP database. The GeneCards, DisGENET and TTD databases were used to obtain caries-related targets. The common targets were derived, and core genes were screened. The enrichment analysis was performed using the DAVID data platform. Molecular docking was performed using AutoDock software. In in vitro antibacterial experiments, first, the 50% minimum inhibitory concentration (MIC50) and the minimum bactericidal concentration (MBC) of the Xinjiang Mori Cortex extract against Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus were determined and the growth curves were measured. The effects of the Xinjiang Mori Cortex extract on acid production, polysaccharide production and adhesion ability of Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus in the planktonic state were determined. The 50% minimum biofilm inhibition concentration (MBIC50) and 50% minimum biofilm reduction concentration (MBRC50) were determined by crystal violet staining, and biofilm morphology was visualized using scanning electron microscopy (SEM).@*Results@#The main active components of the Xinjiang Mori cortex included quercetin, kaempferol, and β-sitosterol. Tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) could be the most important targets of the Xinjiang Mori cortex for the prevention of dental caries. The enrichment analysis results showed that Mori cortex extract may have effects on the AGE-RAGE signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. The antibacterial experiment results showed that the MIC50 values of Xinjiang Mori Cortex extract against Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus were 0.5, 0.5 and 0.25 mg/mL, respectively, and the MBCs were 4.0, 2.0 and 1.0 mg/mL, respectively. The inhibitory effect of Xinjiang Mori Cortex extract on the acid production, polysaccharide production and adhesion ability of three major cariogenic bacteria in the planktonic state was stronger than that of the control group, and the differences were statistically significant (P<0.05). The MBIC50 was 1.0, 1.0, and 0.5 mg/mL, and the MBRC50 was 4.0, 4.0, and 2.0 mg/mL. SEM observation showed that the amount of biofilm formation decreased with the drug concentration compared with the control group.@*Conclusion@#Xinjiang Mori cortex extract can prevent caries through quercetin, kaempferol, and β-sitosterol active ingredients, TNF、IL-6、IL-1β key targets and multiple pathways and inhibit the growth, acid production, polysaccharide production, and adhesion ability of three major cariogenic bacteria in the planktonic state and has some inhibitory effect on corticogenic biofilm formation.

Mechanism of Tumor T Cell Exhaustion from Perspective of ''Sanjiao-Yingwei'' Qi Transformation Malfunction / 中国实验方剂学杂志

In order to promote the innovative application of Sanjiao theory and Yingwei theory， this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases， integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body， and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi， and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion， which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis， which contributes to T cell exhaustion and is correlated with nutrient deprivation， lipid accumulation， and high lactate levels in the immunosuppressed tumor microenvironment， as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction， Shengming decoction， and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation， and hypoxia inducible factor-1α （HIF-1α） may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.

Mechanism of Astragaloside Ⅳ on db/db Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Based on AMPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg-1 by gavage， and the metformin group was given 0.067 g·kg-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.

Determination and Mechanism Prediction of Potential Active Ingredients in Erdongtang Based on UHPLC-QqQ-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L-1）， baicalin（1 078.37-1 411.52 mg·L-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L-1）， timosaponin BⅡ（245.10-604.89 mg·L-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L-1）， rutin（46.91-1 553.61 mg·L-1）， glycyrrhizic acid（55.97-391.47 mg·L-1）， neomangiferin（37.45-127.03 mg·L-1）， nuciferine（0.89-63.48 mg·L-1）， hyperoside（6.96-136.78 mg·L-1）， liquiritin（30.89-122.78 mg·L-1）， liquiritigenin（26.64-110.67 mg·L-1）， protodioscin（58.57-284.26 mg·L-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L-1）， pseudoprotodioscin（5.49-22.96 mg·L-1）， ginsenoside Rb1（7.31-23.87 mg·L-1）， ginsenoside Rg1（10.78-28.33 mg·L-1）， ginsenoside Re（7.78-24.76 mg·L-1）， ophiopogonin D（2.08-4.29 mg·L-1）， methylophiopogonanone A（0.74-1.67 mg·L-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

Establishment of Comprehensive Protection System for Intellectual Property of Single Herbs by Taking Callicarpa nudiflora of Jiuzhitang as An Example / 中国实验方剂学杂志

The development of single Chinese materia medica is an important direction of technological innovation in the field of Chinese materia medica at present， and the study of its comprehensive intellectual property protection system is of great significance to the intellectual property protection of the whole chain of innovative enterprises of single Chinese materia medica. Based on this， this paper takes the comprehensive protection system of intellectual property of Callicarpa nudiflora constructed by Jiuzhitang Pharmaceutical as a model to conduct empirical research， analyzes the protection forms applicable to intellectual property of Chinese materia medica， such as patents， administrative protection， trademarks， designs and intangible cultural heritages， and discusses the valuable and insufficient aspects of the protection system currently constructed by Jiuzhitang Pharmaceutical and puts forward the following suggestions：①paying attention to patent applications for planting/processing methods of raw medicinal materials， ②emphasizing the protection of geographical indications， authentic medicinal herbs， and new plant varieties， ③actively promoting product and technology upgrades， ④applying for data protection during product iteration， ⑤emphasizing the layout timing of patent and administrative protection， ⑥focusing on improving goodwill， ⑦enhancing awareness of intellectual property protection and promoting deep integration of industry， academia， and research. We hope that innovative enterprises engaged in the development of single Chinese materia medica can learn from the experience of the case， and optimize the strategy to better protect related products.

Mechanism of Qizhenziyin mixture in the treatment of hypogonadism based on network pharmacology analysis and molecular docking / 药学实践杂志

Objective To investigate the mechanism of Qizhenziyin mixture in the treatment of hypogonadism by using the network pharmacology approach. Methods The active components of Qizhenziyin mixture were obtained by searching TCMSP ，TCMID and HIT databases.The related targets of candidate compounds were obtained by searching STITCH databases. The potential targets of Qizhenziyin mixture in the treatment of hypogonadism were obtained by mapping the disease genes of hypogonadism with Genecards and DisGeNet databases. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction （PPI） network was constructed by introducing Cytoscape software. The mechanism of Qizhenziyin mixture in the treatment of hypogonadism was explained through the enrichment analysis of GO, KEGG and molecular docking technology. Results A total of 148 drug-disease chemical compounds, 96 drug-disease intersection targets, 1085 disease targets were obtained；the components for treating diseases are: quercetin，kaempferol, luteolin, etc; enrichment analysis of GO revealed 1792 biological processes （BP）, 31 cellular components (CC) and 79 molecular functions (MF)；the results of KEGG pathway enrichment analysis indicated such as FOXO signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, etc.The results of molecular docking showed that kaempferol and LEP had the best and stable binding energy. Conclusion The active components of Qizhenziyin mixture may play a role of the treatment of hypogonadism by improving insulin resistance and the expression of testosterone synthetase of Leydig cells.

Screening and bioinformatics analysis of key autophagy-related genes in alcoholic hepatitis / 器官移植

Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

Pharmacotherapy plan for metastatic hormone-sensitive prostate cancer：a network meta-analysis / 中国药房

OBJECTIVE To determine the optimal therapeutic plan for metastatic hormone-sensitive prostate cancer （mHSPC）， and to provide reference for clinical decision-making. METHODS Retrieved from Medline， Embase， BIOSIS preview， the Cochrane Library and ClinicalTrials. gov systematically， randomized controlled trials about mHSPC therapy， with overall survival （OS） and radiographic progression-free survival （rPFS） as efficacy outcomes and the incidence of serious adverse events （SAEs） as safety outcome， were collected during the inception-Mar. 2022. Two researchers independently screened the literature， extracted data， and evaluated the risk of bias for the included study before conducting a Bayesian network meta-analysis. RESULTS Eight studies with 9 437 patients were finally included. The effectiveness and safety of 7 therapy plans were compared [abiraterone acetate， apalutamide， darolutamide+docetaxel， docetaxel， enzalutamide， standard non-steroidal antiandrogen （SNA） in addition to ADT， and ADT alone]. In terms of efficacy index， the most beneficial regimen （except for ADT+SNA） for OS was ADT+darolutamide+docetaxel （HR＝0.54， 95%CI of 0.44-0.66）， followed by ADT+abiraterone acetate （HR＝0.64，95%CI of 0.57- 0.71）， apalutamide （HR＝0.65， 95%CI of 0.53-0.79）， enzalutamide （HR＝0.66， 95%CI of 0.53-0.82）； the least beneficial regimen for OS was ADT+docetaxel （HR＝0.79， 95%CI of 0.71-0.88）. The most beneficial regimen （except for ADT+SNA） for rPFS was ADT+enzalutamide （HR＝0.39， 95%CI of 0.30-0.50）， followed by ADT+apalutamide （HR＝0.48， 95%CI of 0.39- 0.60）， abiraterone acetate （HR＝0.57， 95%CI of 0.51-0.64）， docetaxel （HR＝0.62， 95%CI of 0.56-0.69）. The results of the tumor- loading subgroup analysis were the same. In terms of safety， ADT+darolutamide+docetaxel （OR＝25.86， 95%CI of 14.08-51.33）， and ADT+docetaxel （OR＝23.35， 95%CI of 13.26-44.81） were associated with markedly increased SAEs； the incidence of SAEs caused by ADT+abiraterone acetate （OR＝1.42，95%CI of 1.10-1.82） was slightly increased， and those of other therapy plans had no significant difference. CONCLUSIONS Compared with ADT alone， ADT+ darolutamide+docetaxel may provide the most significant OS benefit， but the incidence of SAEs is increased greatly； compared with ADT+docetaxel， ADT+abiraterone acetate， apalutamide or enzalutamide provide more OS benefits. ADT+enzalutamide provide optimal rPFS benefits with no increased SAEs.

Optimization of water extraction technology of Xiangqin jiere granules by orthogonal design based on G1-entropy weight compared with BP neural network / 中国药房

OBJECTIVE Optimizing the water extraction technology of Xiangqin jiere granules. METHODS The orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters. RESULTS The water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test. CONCLUSIONS The water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.

Traditional Chinese Medicine Syndromes in Depressive Episodes of Bipolar Disorder Based on Cluster Analysis and Bayesian Network：A Cross-sectional Study / 中医杂志

ObjectiveTo explore the elements， distribution and characteristics of traditional Chinese medicine （TCM） syndromes in depressive episodes of bipolar disorder （BD）. MethodsBasic information， along with the four examination information， the Hamilton Depression Scale and Young Mania Rating Scale scores， were collected from 293 outpatients with BD at Beijing Anding Hospital， Capital Medical University. The four examination information with an occurrence rate greater than 12% were retained. The R language “dist” function was used to calculate the distances between samples using the Euclidean distance method. The hierarchical clustering of the four examination information was performed using the “hclust” function and the squared Euclidean distance method. A team of five researchers was formed to determine the nature and location of the essential elements of TCM syndrome in BD based on the clustering results. The PC algorithm was used to construct a Bayesian network model of the essential elements. The working group combined the essential elements of TCM syndromes in the Bayesian network according to the reference model results， and then extracted common TCM syndromes. The score of each patient based on the essential elements was matched with the common TCM syndromes to determine the syndrome type of each patient. The working group then performs conformity and revision based on this， obtaining the final distribution of TCM syndromes for the patients. ResultsThere were 77 common TCM symptoms in BD with a frequency greater than 12%. The top 15 symptoms with higher frequencies were slippery pulse， mental fatigue and lack of strength， wiry pulse， excessive rumination， preference for solitude， vexation， agitation and irritability， dry mouth， palpitations， profuse dreaming， unwarranted worries， chest oppression， thin white coating， amnesia， frequent sighing， and poor appetite. TCM syndrome elements of BD can be grouped into 11 categories. The nature of disease-related essential elements included fire， qi deficiency， blood deficiency， qi counterflow， yin deficiency， dampness， heat， fire from constraint， and phlegm. The location of disease-related essential elements included heart， liver， spleen， stomach， kidney， bladder channel， and gallbladder. By constructing a Bayesian network model and considering the opinions from the experts， six common syndromes of BD were identified， among which the highest proportion was heart-stomach heat accumulation， accounting for 27.99% （82 cases）， followed by heart-spleen deficiency （55 cases， 18.77%）， non-interaction between the heart and the kidney （49 cases， 16.72%）， liver constraint and blood deficiency （42 cases， 14.33%）， heart qi deficiency （37 cases， 12.63%）， and damp-heat in the liver and gallbladder （28 cases， 9.56%）. ConclusionsThe nature of disease-related elements of BD are predominantly fire and heat， while the location of disease-related essential elements are primarily associated with the heart， liver， and spleen. The most common TCM syndromes are heart-stomach heat accumulation and heart-spleen deficiency.

Analysis of Antidepressant Quality Markers of Bupleuri Radix Before and After Vinegar-processing Based on UPLC-Q-TOF-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the antidepressant quality markers（Q-Marker） of Bupleuri Radix（BP） before and after vinegar-processing by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， multivariate statistical analysis and network pharmacology. MethodUPLC-Q-TOF-MS was used to analyze the chemical basis of raw and vinegar-processed products of BP， and principal component analysis（PCA） orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to identify the differential components in BP that changed significantly before and after vinegar-processing， which were regarded as candidate quality markers（Q-Marker）. Then the disease-drug-component-target network related to antidepressant effect of BP was constructed by network pharmacology， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined. Rats were randomly divided into blank group， model group， fluoxetine group（2.67 mg·kg-1） and total saponin group（0.72 mg·kg-1）， except the blank group， rats in the other groups were subjected to chronic unpredictable mild stress（CUMS）. Three weeks after the start of modeling， rats in each administration group were given the corresponding dose of drugs once a day for 4 weeks， and rats in the blank and model groups were given normal saline with dose of 10 mL·kg-1. At 1 day before modeling， 21 days and 28 days after administration， body mass weighing， sucrose preference test and open field test were performed on each group . After 28 days of administration， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression levels of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（Akt）， mammalian target of rapamycin（mTOR）， glycogen synthase kinase-3β（GSK-3β）， forkhead box transcription factor O3a（FoxO3a） and β-catenin in hippocampal tissues of rats in each group， while protein expression levels of PI3K， Akt， mTOR and FoxO3a in hippocampal tissues of rats in each group were detected by Western blot. ResultThere were 19 components in BP showed significant changes before and after vinegar-processing， and 9 components such as saikosaponin A， saikosaponin B1， saikosaponin B2， saikosaponin C and saikosaponin D were identified as potential Q-Marker through S-plot differential marker screening. Combined with the disease-drug-component-target network， saikosaponin A， saikosaponin B1， saikosaponin B2 and saikosaponin D were identified as antidepressant Q-Marker of raw and vinegar-processed products of BP. According to the results of pharmacodynamic tests， after 28 d of administration， compared with the blank group， the body mass， sucrose preference index and open field total score of rats in model group， fluoxetine group and total saponin group decreased significantly（P<0.01）. Compared with the model group， the body mass， sucrose preference index and open field total score in total saponin group increased significantly（P<0.01）. Compared with the blank group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the model group decreased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a increased significantly（P<0.05）. Compared with the model group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the total saponin group were increased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a decreased significantly（P<0.05）. Compared with the blank group， the protein expression levels of Akt and mTOR in hippocampus of the model group decreased significantly（P<0.01）， while the protein expression levels of PI3K and FoxO3a increased significantly（P<0.01）. Compared with the model group， the expression level of Akt in hippocampus of the total saponin group increased significantly（P<0.01）， the mTOR expression level was increased but not statistically significant， while the protein expression levels of PI3K and FoxO3a decreased significantly（P<0.01）. ConclusionThe chemical constituents of BP changed greatly after vinegar-processing， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined by chemical basis， pharmacodynamics， network pharmacology and signaling pathway， which provided a reference for further research on quality control， pharmacodynamic substance basis and processing mechanism of BP.

MobileNetV3 network-based diagnosis of caries and periapical periodontitis from periapical films / 口腔疾病防治

Objective@#To research the effectiveness of deep learning techniques in intelligently diagnosing dental caries and periapical periodontitis and to explore the preliminary application value of deep learning in the diagnosis of oral diseases@*Methods@#A dataset containing 2 298 periapical films, including healthy teeth, dental caries, and periapical periodontitis, was used for the study. The dataset was randomly divided into 1 573 training images, 233 validation images, and 492 test images. By comparing various neural network models, the MobileNetV3 network model with better performance was selected for dental disease diagnosis, and the model was optimized by tuning the network hyperparameters. The accuracy, precision, recall, and F1 score were used to evaluate the model's ability to recognize dental caries and periapical periodontitis. Class activation map was used to visualization analyze the performance of the network model@*Results@#The algorithm achieved a relatively ideal intelligent diagnostic effect with precision, recall, and accuracy of 99.42%, 99.73%, and 99.60%, respectively, and the F1 score was 99.57% for classifying healthy teeth, dental caries, and periapical periodontitis. The visualization of the class activation maps also showed that the network model can accurately extract features of dental diseases.@*Conclusion@#The tooth lesion detection algorithm based on the MobileNetV3 network model can eliminate interference from image quality and human factors and has high diagnostic accuracy, which can meet the needs of dental medicine teaching and clinical applications.

Liver Injury Caused by Psoraleae Fructus： A Review / 中国实验方剂学杂志

Psoraleae Fructus （PF） is a non-toxic Chinese herbal medicine， while the liver injury caused by PF has aroused wide concern in recent years. At present， animal experiments and in vitro studies have been carried out to explore the mechanism， targets， and toxic components of PF in inducing liver injury， which， however， have differences compared with the actual conditions in clinical practice， and there are still some potential hepatotoxic components and targets of PF that have not been discovered. With the continuous progress in systems biology， establishing the drug-induced liver injury model and the liver injury prediction model based on network toxicology can reduce the cost of animal experiments， improve the toxicity prediction efficiency， and provide new tools for predicting toxic components and targets. To systematically explain the characteristics of liver injury in the application of PF and explore the potential hepatotoxic components and targets of PF， we reviewed the related articles published by China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， and PubMed from 1962 to 2021 and analyzed the characteristics and influencing factors of liver injury caused by PF in the patients. Furthermore， we summarized the chemical components of PF and the components entering blood. By reviewing the mechanism， targets， and components of PF in inducing liver injury that were discovered by in vivo and in vitro experiments， we summarized the known compounds in PF that may cause liver injury. Finally， the current methods for building the prediction model of PF-induced liver injury were summarized， and the predicted toxic components and targets were introduced. The possible factors of PF in causing liver injury were explained from three aspects： clinical characteristics， preclinical studies， and computer-assisted network prediction， which provide a reference for predicting the risk of PF-induced liver injury.

Transcriptome Sequencing on Treatment of Kidney Deficiency and Blood Stasis-thin Endometrium in Rats with Bushen Huoxue Prescription Through Enema / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Bushen Huoxue enema in treating the rat model of kidney deficiency and blood stasis-thin endometrium （KDBS-TE） by transcriptome sequencing. MethodThe rat model of KDBS-TE was established by administration of tripterygium polyglycosides tablets combined with subcutaneous injection of adrenaline. The pathological changes of rat endometrium in each group were then observed. Three uterine tissue specimens from each of the blank group， model group， and Bushen Huoxue enema group were randomly selected for transcriptome sequencing. The differentially expressed circRNAs， lncRNAs， and miRNAs were screened， and the disease-related specific competitive endogenous RNA （ceRNA） regulatory network was constructed. Furthermore， the gene ontology （GO） functional annotation and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the mRNAs in the network. ResultCompared with the blank group， the model group showed endometrial dysplasia， decreased endometrial thickness and endometrial/total uterine wall thickness ratio （P<0.01）， and differential expression of 18 circRNAs， 410 lncRNAs， and 7 miRNAs. Compared with the model group， the enema and estradiol valerate groups showed improved endometrial morphology and increased endometrial thickness and ratio of endometrial to total uterine wall thickness （P<0.05）. In addition， 21 circRNAs， 518 lncRNAs， and 17 miRNAs were differentially expressed in the enema group. The disease-related specific circRNA-miRNA-mRNA regulatory network composed of 629 nodes and 664 edges contained 2 circRNAs， 34 miRNAs， and 593 mRNAs. The lncRNA-miRNA-mRNA regulatory network composed of 180 nodes and 212 edges contained 5 lncRNAs， 10 miRNAs， and 164 mRNAs. The mNRAs were mainly enriched in Hippo signaling pathway， autophagy-animal， axon guidance， etc. ConclusionBushen Huoxue enema can treat KDBS-TE in rats by regulating specific circRNAs， lncRNAs， and miRNAs in the uterus and the ceRNA network.

Network Pharmacology in Research on Efficacy of Traditional Chinese Medicine and Compound Prescriptions / 中国实验方剂学杂志

The efficacy of traditional Chinese medicine （TCM） and compound prescriptions is confirmed based on practical experience. It is a highly generalized expression of the clinical characteristics and scope of prescriptions and a unique expression of the medical effects of TCM. Network pharmacology， as a cross-disciplinary field based on the theory of systems biology and multi-level analysis of biological systems， has become a common virtual screening tool in TCM research and gradually developed with the progress in big data and artificial intelligence. In the context of modern medicine， the efficacy of TCM compound prescriptions has a vague concept and lacks scientific evidence. Elucidating the connotation of TCM efficacy and guiding TCM theoretical research has become one of the hotspots and difficulties in TCM research. This article explores the feasibility of using network pharmacology for the research on the efficacy of TCM compound prescriptions and investigates whether the research results can represent part of the efficacy of prescriptions. Furthermore， the research platforms and algorithms in this field are summarized. The research ideas and existing problems in this field are proposed from the aspects of efficacy concept embodiment， target screening， result verification， efficacy network building， and homogenization avoiding of network pharmacology research results. Finally， the future development directions are prospected. This article is expected to provide a reference for exploring the modern biological basis of the efficacy of TCM and compound prescriptions and for the clinical application and theoretical research of TCM.

A enfermeira que virou ilustração e os quilombolas contra a covid-19 no Pará / The nurse who became an illustration and the quilombolas against covid-19 in Pará / La enfermera que se convirtió en ilustración y los quilombolas contra el covid-19 en Pará

Este artigo tem como objetivo descrever as experiências de comunicação sobre saúde, desenvolvidas com comunidades quilombolas na Amazônia, através de mídias sociais durante a pandemia de covid-19. A disseminação de mensagens educativas foi uma das alternativas utilizadas pelas organizações quilombolas e por seus parceiros, para proporcionar informação e orientação sobre saúde. São apresentadas experiências acumuladas a partir das ações desenvolvidas por voluntários, no período de 2020 a 2022. Entre as mídias digitais e as estratégias utilizadas, destacam-se os cards digitais produzidos e distribuídos, principalmente, por meio do aplicativo de mensagens WhatsApp. Refletimos sobre a importância do uso das mídias sociais como instrumentos de comunicação educacional para a promoção da saúde e prevenção da covid-19, em uma era tecnológica que potencializa trocas intensas de informações e conhecimentos. No caso abordado, a educação sobre saúde, através de mídias sociais/digitais, mostrou-se um instrumento essencial para a minimização dos impactos da covid-19 na população quilombola

This article aims to describe the health communication experiences developed with quilombola commu-nities in the Amazonia through social media in the covid-19 pandemic. The dissemination of educational messages was one of the alternatives used by quilombola organizations and their partners to provide health information and guidance. Accumulated experiences are presented based on the actions carried out by volunteers in the period from 2020 to 2022. Among the digital media and strategies used, most important are the digital cards produced and distributed mainly through the WhatsApp Messenger. We reflect on the importance of using social media as educational communication tools for health promotion and prevention of covid-19, in a technological era that intensifies intense exchanges of information and knowledge. In the case approached here, health education through social/digital media proved to be an essential tool for minimizing the impacts of covid-19 on the quilombola population

Este artículo tiene como objetivo describir las experiencias de comunicación en salud desarrolladas con comunidades quilombolas de la Amazonia a través de las redes sociales durante la pandemia de covid-19. La difusión de mensajes educativos fue una de las alternativas utilizadas por las organizaciones quilombolas y por sus aliados para proporcionar información y orientación sobre salud. Se presentam experiencias acumuladas a partir de las acciones desarrolladas por voluntarios en el periodo de 2020 a 2022. Entre los medios digitales y estrategias utilizados, se destacan las tarjetas digitales producidas y distribuidas principalmente a través de la aplicación de mensajería WhatsApp. Reflexionamos sobre la importancia de utilizar los medios sociales como herramientas de comunicación educativa para la promoción de la salud y la prevención de la covid-19, en una era tecnológica que potencia intensos intercambios de información y conocimiento. En el caso relatado, la educación para la salud a través de medios sociales/digitales demostró ser una herramienta esencial para minimizar los impactos de la covid-19 en la población quilombola

Práticas educacionais colaborativas em saúde mediadas pelas tecnologias da informação e comunicação: uma revisão de literatura / Collaborative educational practices in health mediated by information and communication technologies: a literature review / Prácticas educativas colaborativas en salud mediadas por las tecnologías de la información y comunicación: una revisión de literatura

O objetivo do presente estudo foi identificar elementos estruturantes do processo de trabalho das redes educacionais colaborativas em saúde mediadas por tecnologias de informação e comunicação, assinalando suas características-chave e sua dinâmica de funcionamento. Trata-se de uma revisão de escopo, realiza-da nas bases de dados: Medline, Lilacs e no portal Oasisbr. Foram encontrados 1.499 estudos, dos quais, oito atenderam aos critérios de inclusão. Os resultados da investigação apontam as práticas educacionais colaborativas em saúde mediados por essas tecnologias como processos amplos e complexos, envolvendo a associação de diversos fatores. Destacam-se a dimensão técnico-pedagógica, a gestão estratégica, o gerenciamento do fluxo de informações, os aspectos relacionais, as competências de cada membro e a mediação do processo colaborativo. A integração dos diferentes aspectos da rede traduz um conjunto de desafios para a estruturação dos processos colaborativos que não se limita à pura acumulação cognitiva, mas vincula-se a processos de aprendizagem e desenvolvimento dos sujeitos

The aim of the present study was to identify structural elements of the work process of collaborative educational networks in health, mediated by information and communication technologies, by pointing out its key characteristics and its operating dynamics. This is a scope review, accomplished in the following databases Medline and Lilacs and in the Oasisbr portal. A total of 1.499 studies were found, and eight of them met the inclusion criteria. The search results indicate the collaborative educational practices in health mediated by these technologies as broad and complex processes, involving the association of several factors. The technical-pedagogical dimension, the strategic management, the management of the information flow, the relational aspects, the competencies of each member, and the mediation of the collaborative process are highlighted. The integration of the different aspects of the network translates a set of challenges for the structuring of collaborative processes, which is not limited to pure cognitive accumulation, but is bound to learning processes and to the subjects' development.

El objetivo del presente estudio es identificar elementos estructurantes del proceso de trabajo de las redes educativas colaborativas en salud mediadas por tecnologías de la información y comunicación, señalando sus características claves y su dinámica de funcionamiento. El trabajo presenta una revisión de escopo, realizada en las bases de datos: Medline, Lilacs y en el portal Oasisbr. Fueron encontrados 1.499 estudios, de los cuales ocho cumplieron los criterios de inclusión. Los resultados de la investigación apuntan a las prácticas educativas colaborativas en salud mediadas por estas tecnologías como procesos amplios y com-plejos, que abarcan la asociación de diversos factores. Se destacan la dimensión técnico-pedagógica, la gestión estratégica, el gerenciamiento del flujo de información, los aspectos relacionales, las competencias de cada miembro y la mediación del proceso colaborativo. La integración de los diferentes aspectos de la red traduce un conjunto de desafíos para la estructuración de los procesos colaborativos, que no se limitan a la acumulación cognitiva, sino que se vinculan a los procesos de aprendizaje y desarrollo de los sujetos

Tensiones en cotidianidad de jóvenes universitarios: estudio en tres universidades del Quindío

(analítico) Con el tiempo, el acceso de los jóvenes a la universidad ha sido mayor; sin embargo, una serie de factores puede hacer que, en este tránsito, los estudiantes experimenten tensiones que influyen en su salud integral. Por ello, conocer cuáles son las tensiones que viven los estudiantes en el contexto universitario constituye un punto de partida para su bienestar. Se realizó una investigación cualitativa con diseño fenomenológico, mediante grupos focales y entrevistas se-miestructuradas. La categorización se realizó con el Software IRaMuTeQ y su análisis mediante la técnica de análisis de contenido. Se encontró que las redes de apoyo pueden convertirse en agentes de tensión: red familiar, expectativas frente al desempeño académico; red social, necesidad de encajar y establecer relaciones, y red universitaria, metodologías de algunos profesores y desconocimiento de infraestructura.

(analytical) Over time, the access of young people to the university has been greater; however, a series of factors can cause students to experience tensions during this transit that influence their overall health. Therefore, knowing what are the tensions that students experience in the university context constitutes a starting point for their well-being. A qualitative research with a phenomenological design was carried out, through focus groups and semi-structured interviews. The categorization was carried out with the IRaMuTeQ Software and its analysis using the content analysis technique. It was found that support networks can become agents of tension: family network, expectations regarding academic performance; social network, need to fit in and establish relationships, and university network, methodologies of some professors and lack of knowledge of infrastructure.

(analítico) Com o passar do tempo, o acesso dos jovens à universidade foi maior; no entanto, uma série de fatores pode fazer com que os alunos experimentem tensões durante esse trânsito que influenciam sua saúde geral. Portanto, saber quais são as tensões que os alunos vivenciam no contexto universitário constitui um ponto de partida para o seu bem-estar. Realizou-se uma pesquisa qualitativa de delineamento fenomenológico, por meio de grupos focais e entrevistas semiestruturadas. A categorização foi realizada com o Software IRaMuTeQ e sua análise por meio da técnica de análise de conteúdo. Constatou-se que as redes de apoio podem se tornar agentes de tensão: rede familiar, expectativas em relação ao desempenho acadêmico; rede social, necessidade de se enquadrar e estabelecer relacionamentos, e rede universitária, metodologias de alguns professores e desconhecimento de infraestrutura.

Maternidade distante do país de origem: "aqui a gente não tem uma aldeia" / Maternity far from the country of origin: "here we do not have a village" / Maternidad lejos del país de origen: "aquí no tenemos pueblo"

O presente estudo é um recorte de uma pesquisa mais ampla sobre a experiência da maternidade de mulheres brasileiras migrantes. Ele tem como objetivo investigar o apoio recebido por elas no processo de tornar-se mãe. Trata-se de uma pesquisa qualitativa na qual foram realizadas, em 2022, sete entrevistas com mulheres brasileiras que vivenciaram gestação, parto e primeiro ano de vida do filho (a) em Portugal, Reino Unido, Itália, Espanha e França. Os resultados apontam para a relevância da presença de pessoas que compartilham da mesma cultura de origem na construção da maternidade e na rede de apoio durante a perinatalidade. Conclui-se que o distanciamento da rede familiar, de amigos e de referenciais da cultura de origem da mulher migrante gerou o aumento das sobrecargas psíquica e física inerentes à maternidade. Ao mesmo tempo, de acordo com as participantes, o distanciamento da família e da cultura de origem proporcionou maior liberdade e abertura para a construção da maternidade, provendo novas representações culturais que contribuíram para a construção de sua forma de ser mãe.(AU)

This study is a segment of a broader research project on the maternity experience of Brazilian migrant women. It aims to investigate the support received by these women in the process of becoming mothers. It encompasses a qualitative research study involving seven interviews conducted in 2022 with Brazilian women who experienced pregnancy, childbirth, and the first year of their child's life in Portugal, the United Kingdom, Italy, Spain, and France. The findings highlight the importance of having individuals sharing the same cultural background in the construction of motherhood and in the support network during the perinatal period. The distance from the family network, friends, and references of the migrant woman's culture of origin generated an increase in the psychic and physical burdens inherent to motherhood. Simultaneously, according to the participants, distancing from family and their cultural origins provided greater freedom and openness in constructing motherhood, offering new cultural representations that contributed to shaping their way of being mothers. (AU)

El presente estudio es parte de una investigación más amplia acerca de la experiencia de la maternidad de las mujeres migrantes brasileñas. Tiene como objetivo investigar el soporte recibido por ellas en el proceso de convertirse en madre. Se trata de una investigación cualitativa en la que, en 2022, se realizaron siete entrevistas con mujeres brasileñas que vivieron el embarazo, el parto y el primer año de vida de su hijo en Portugal, Reino Unido, Italia, España y Francia. Los resultados apuntan para la relevancia de la presencia de personas que comparten la misma cultura de origen en la construcción de la maternidad y en la red de apoyo durante la perinatalidad. Se concluye que el alejamiento de la red familiar, amigos y puntos de referencia de su cultura de origen de la mujer migrante ha generado un aumento de las sobrecargas psíquicas y físicas inherentes a la maternidad. Al mismo tiempo, según las participantes, el alejamiento de la familia y de la cultura de origen les ha proporcionado una mayor libertad y apertura para la construcción de la maternidad, brindando nuevas representaciones culturales que contribuyeron para la construcción de su forma de ser madre. (AU)