Automatic detection and classification of disease in citrus fruit and leaves using a customized CNN based model / Detección y clasificación automática de enfermedades en frutas y hojas de cítricos utilizando un modelo basado en CNN personalizado

India's commercial advancement and development depend heavily on agriculture. A common fruit grown in tropical settings is citrus. A professional judgment is required while analyzing an illness because different diseases have slight variati ons in their symptoms. In order to recognize and classify diseases in citrus fruits and leaves, a customized CNN - based approach that links CNN with LSTM was developed in this research. By using a CNN - based method, it is possible to automatically differenti ate from healthier fruits and leaves and those that have diseases such fruit blight, fruit greening, fruit scab, and melanoses. In terms of performance, the proposed approach achieves 96% accuracy, 98% sensitivity, 96% Recall, and an F1 - score of 92% for ci trus fruit and leave identification and classification and the proposed method was compared with KNN, SVM, and CNN and concluded that the proposed CNN - based model is more accurate and effective at identifying illnesses in citrus fruits and leaves.

El avance y desarrollo comercial de India dependen en gran medida de la agricultura. Un tipo de fruta comunmente cultivada en en tornos tropicales es el cítrico. Se requiere un juicio profesional al analizar una enfermedad porque diferentes enfermedades tienen ligeras variaciones en sus síntomas. Para reconocer y clasificar enfermedades en frutas y hojas de cítricos, se desarrolló e n esta investigación un enfoque personalizado basado en CNN que vincula CNN con LSTM. Al utilizar un método basado en CNN, es posible diferenciar automáticamente entre frutas y hojas más saludables y aquellas que tienen enfermedades como la plaga de frutas , el verdor de frutas, la sarna de frutas y las melanosis. En términos de desempeño, el enfoque propuesto alcanza una precisión del 96%, una sensibilidad del 98%, una recuperación del 96% y una puntuación F1 del 92% para la identificación y clasificación d e frutas y hojas de cítricos, y el método propuesto se comparó con KNN, SVM y CNN y se concluyó que el modelo basado en CNN propuesto es más preciso y efectivo para identificar enfermedades en frutas y hojas de cítricos.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.@*METHODS@#A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.@*RESULTS@#Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.@*CONCLUSION@#Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Study on the treatment of cerebral infarction with Chinese medicine Shenmajingfu granule by network pharmacology / 药学实践杂志

Objective To explore the material basis and mechanism of the Chinese medicine Shenmajingfu granules in the treatment of cerebral infarction. Methods The potential active ingredients and targets of Shenmajingfu granules were retrieved through TCMSP, ETCM database and TCM Database. The related target genes of cerebral infarction were searched from OMIM database. The common targets of Shenmajingfu granules and cerebral infarction were obtained by the intersection method. Cytoscape was used to construct active components of Shenmajingfu granules-targets network. Protein-protein interaction network was constructed by STRING software. DAVID database was used for GO and KEGG enrichment analysis. Results The 183 potential active ingredients of Shenmajingfu granules were screened out. 1785 potential targets were screened in the TCMSP database, including 30 targets related to cerebral infarction. These target genes were mainly involved in the inflammatory response and apoptosis process, involving the TNF signaling pathway, HIF-1 signaling pathway and NF-κB signaling pathway. Conclusion The therapeutic effect of Shenmajingfu granules on cerebral infarction may be related to the regulation of inflammatory response, improvement of impaired neurological function and protection of cerebral ischemia-reperfusion injury.

Optimization of ethanol extraction process for Yihuang powder by orthogonal experiment combined with AHP and GA-BP neural network / 中国药房

OBJECTIVE To optimize ethanol extraction process of Yihuang powder. METHODS An orthogonal experiment was designed by reflux extraction with ethanol volume fraction， liquid-to-material ratio， and extraction time as investigation factors. The parameters used were the contents of hesperidin， nobiletin， tangeretin， gallic acid， chebulagic acid， chebulinic acid， liquiritin， glycyrrhizin， eugenol， and the paste-forming rate. The analytic hierarchy process （AHP） was used to calculate the comprehensive score. The optimal ethanol extraction process parameters of Yihuang powder were determined by verifying the results predicted by orthogonal experiment and genetic algorithm （GA）-back propagation neural network （BP neural network）. RESULTS The optimal ethanol extraction process parameters， as optimized by orthogonal experiment， were as follows: ethanol volume fraction of 60%， liquid-solid ratio of 14∶1 （mL/g)， extraction time of 90 min， and extraction for 2 times. The comprehensive score obtained by verification was 79.19. Meanwhile， the optimal ethanol extraction process parameters， optimized by GA-BP neural network， were ethanol volume fraction of 65%， liquid-solid ratio of 14∶1 （mL/g )， extraction time of 60 min， and extraction for 2 times. The comprehensive score obtained by verification was 85.30， higher than the results obtained from orthogonal experiment. CONCLUSIONS The optimization method of orthogonal experiment combined with GA-BP neural network is superior to the traditional orthogonal experiment optimization method. The optimized ethanol extraction process of Yihuang powder is stable and reliable.

Mechanism of Cuscutae Semen to Control Premature Ovarian Failure Based on Lipid and Atherosclerosis Pathways / 中国实验方剂学杂志

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg-1·d-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg-1·d-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E2）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E2， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.

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.