1.Bioinformatics analysis on key genes related to prognosis,diagnosis,and immune cell infiltration of hepatocellular carcinoma and their potential therapeutic drugs
Jinlian LI ; Lanzhen HUANG ; Xishi HUANG ; Kangzhi LI ; Jiali JIANG ; Miaomiao ZHANG ; Qunying WU
Journal of Jilin University(Medicine Edition) 2024;50(4):1062-1075
Objective:To screen the key genes related to the prognosis,diagnosis,and immune infiltration of the hepatocellular carcinoma(HCC)patients by bioinformatics analysis methods,and to analyze their potential therapeutic drugs.Methods:The HCC gene expression profile data and corresponding clinical informations of the HCC patients were downloaded from the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database.The R software package limma was used to screen the differentially expressed genes(DEGs)in HCC.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the DEGs.The STRING database was used to construct the protein-protein interaction(PPI)network;the Cytoscape software was used to visualize the PPI network and screen the key genes;Kaplan-Meier survival curve and LASSO regression algorithm were used to identify the key genes related to the HCC prognosis;external data sets were used to validate their expressions and analyze the diagnostic efficacy;CIBERSORT algorithm was used to detect the relationship between the expression of prognosis-related key genes and HCC immune cell infiltration.The MiRNet and Network Analyst databases were used to construct the microRNA(miRNA)-key gene mRNA and transcription factors(TFs)-key gene mRNA molecular regulatory networks;CMap database was used to screen the potential small molecule drugs for HCC treatment.Results:A total of 146 DEGs were screened,including 30 upregulated genes and 116 downregulated genes.The GO functional enrichment analysis and KEGG pathway enrichment analysis results showed that the DEGs were significantly enriched in biological processes(BP)such as steroid,alkene compound,and hormone metabolism,as well as signaling pathways such as retinol metabolism,drug metabolism-cytochrome P450(CYP450),complement and coagulation cascades.The PPI network analysis identified 14 key genes,among which formimidoyltransferase cyclodeaminase(FTCD),secreted phosphoprotein 2(SPP2),thrombin-antithrombin complex(TAT),complement C6(C6),and cytochrome CYP450 family member 2C9(CYP2C9)were significantly associated with the prognosis,clinical pathological stage,and histological grade of the HCC patients and also had high diagnostic efficacy for HCC and were closely related to immune cell infiltration in HCC.Hsa-mir-182-5p,CUT-like homeobox 1(CUX1),early growth response 1(EGR1),SMAD family member 4(SMAD4),and tumor protein P53(TP53)were identified as the important regulators targeting the above-mentioned prognosis-related key genes.DL-thiorphan,promethazine,and apigenin may have the therapeutic effects on HCC.Conclusion:FTCD,SPP2,TAT,C6,and CYP2C9 may be the potential targets for the diagnosis,prognosis,and treatment of HCC.Three predicted small molecule drugs,DL-thiorphan,promethazine,and apigenin,may provide the references for the development of therapeutic drugs for HCC.
2.Comparison of two kinds of cervical ripening balloons in promoting full-term pregnancy cervical mature and inducing labor
Na LIU ; Yi ZHU ; Lanzhen ZHANG
The Journal of Practical Medicine 2018;34(8):1301-1304
Objective To explore the clinical effects of single-cavity and COOK cervical ripening balloon in promoting full-term pregnancy cervical mature and inducing labour. Methods 126 puerpera who were expect-ant in the obstetrics department of our hospital were selected from January 2016 to June 2017,and all of the puer-pera were induced labor by cervical ripening balloon.In 61 of them,single-cavity balloon was used,and 65 cases were induced labor by COOK balloon. Determining the cervical ripening situation,the time needed for inducing efficient uterine contraction,the first stage of labor time,the total labor time,vaginal delivery rate,natural labor situation,postpartum hemorrhage,amniotic fluid turbidity,puerperal infection and newborn asphyxia of the two groups.Results the time needed for inducing efficient uterine contraction of the two groups were(16.39±2.68)h, (14.54 ± 3.30)h,and the two groups were statistically different(P<0.05).There were no statistically significant differences in other items of two groups(P>0.05).Conclusion single-cavity balloon and COOK balloon are sim-ilar in promoting full-term pregnancy cervical ripening.The difference is that the time needed for inducing efficient uterine contraction of the single-cavity balloon is longer than COOK balloon,but have no adverse effect to the puer-pera and the newborn.Both types of balloons are recommended to be used in promoting full-term pregnancy cervical ripening and inducing labor.
3.Research Process of Chemical Constituents and Pharmacological Effects of Tibetan Medicine Triphala
Kun ZHOU ; Ping JIAN ; Wenyi LIANG ; Linjin LIANG ; Yaping CUI ; Ting YE ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(9):1608-1614
Triphala consists of Terminalia chebula Retz, Terminalia bellirica (Gaertn.) Roxb. and Phyllanthus emblica L, which are made into Dasanguo Powder. Triphala is rich in a variety of chemical components, including tannins, phenolic acids, triterpenoids and flavonoids. The content of tannin is abundant in Triphala, which are often used as the main indicators of analysis. Modern research found that Triphala has a variety of pharmacological activities such as prevention of gastrointestinal diseases, antibacterial, anti-inflammatory, anti-oxidation, anti-tumor and so on. This paper briefly summarized the chemical constituents and pharmacological effects of Triphala, combining the relevant national and international literature in recent years to provide reference for the development and further study of Triphala.
4.Comprehensive Evaluation of the Quality of Tibetan Medicine Triphala's Tannin Parts Based on There Characteristic Components and the Total Tannin Content
Ting YE ; Yaping CUI ; Linjin LIANG ; Wenyi LIANG ; Ping JIAN ; Kun ZHOU ; LIngfang WU ; Shi LI ; Qi QI ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(9):1615-1621
To determine there characteristic components content of Tibetan Medicine Triphala through establishing a HPLC method and its total tannin content through spectrophotometry. The chromatographic column of Agilent ZORBAX SB-Aq (250 × 4.6 mm, 5 μm) with methanol-0.1% formic acid/water as the mobile phase, the flow rate 1 mL/min, and the detection wavelength 270 nm was applied to determine the Gallic acid, colijing and ellagic acid content in medicinal materials and the tannin parts of Tibetan Medicine Triphala. With the gallic acid as control group, total tannin content of Triphala and its tannin parts was determined through spectrophotometry. It revealed in the HPLC test that the linear range of gallic acid, coracine and ellagic acid was 0.91-4.55 μg, 0.274-1.368 μg and 0.329-2.634 μg respectively. It also showed that the average recovery rates of the three components in the medicinal materials were 101.06%, 101.72%and 100.27% respectively. And the average recovery rates of the three components in the tannins were 100.4%, 100.85%and 101.70% respectively. The result of spectrophotometry showed that gallic acid was linear in1.008-10.08 μg·mL-1, and that the recovery rate of medicinal materials and tannin parts were 100.25% and 100.52% respectively. The method is rapid, accurate and repeatable, and it can provide basis for the quality control of Tribescens and its tannins.
5.Study on Water-Soluble Constituents from Tibetan Medicine Terminalia billirica (Gaert.) Roxb
Shi LI ; Wenyi LIANG ; Linjin LIANG ; Ting YE ; Ping JIAN ; Kun ZHOU ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(9):1622-1626
This paper aimed at investigating the water-soluble constituents of Terminalia billirica (Gaert.) Roxb.Compounds were isolated and purified by Diaion HP-20, Sephadex LH-20, Toyopearl HW-40, MCI gel CHP 20 P and ODS column chromatographies. The chemical structures were elucidated according to spectral data and physicochemical properties. The results showed that ten compounds were isolated and identified as corilagin, salicoside, methyl-α-Darabinofuranoside, 1, 4-dimethyl-β-d-fructopyranose, β-fructopyranose, β-fructofuranose gallic acid, ellagic acid, 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucopyranonside, Chebulagic acid. Except compound 7 and 8, others compounds are separated from Terminalia billirica (Gaert.) Roxb for the first time, and except corilgin, the other compounds are separated from Terminalia for the first time.
6.Study on Rapid Identification of Constituents of Tibetan Medicine Terminalia chebular Retz. by HPLC/LTQ-Orbitrap MSn
Ping JIAN ; Qi QI ; Kun ZHOU ; Wenyi LIANG ; Linjin LIANG ; Ting YE ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(9):1627-1637
The aim of this work was to identify and analyze the chemical constituents of Terminalia chebular Retz by establishing high performance liquid chromatography-linear ion trap/electrostatic field orbitrap combined high resolution mass spectrometry (HPLC-LTQ-Orbitrap MS) technique. With the application of C18 reverse phase column (4.6 mm×250 mm, 5 μm), gradient elution was performed with methanol and water (0.2% acetic acid) as mobile phase.In negative ionization mode, the data of LTQ-Orbitrap was collected. Accurate molecular mass of molecular ion peaks and fragment ions provided by the high-resolution mass spectrometry were compared with the literature and the reference substance to determine the possible structure of the compound. The results indicated that 62 compounds from the extract of Terminalia chebular Retz. were identified, including acids and hydrolysable tannins (60), triterpenoids (2) . There were14 compounds were detected from this specie for the first time. It is proved as an effective method to provide reference for Chemical composition mass spectrometry and the quality control in further phytochemical studies of Terminalia chebular Retz.
7.Study on Quality Evaluation of Terminalia Chebular Based on Simultaneous Determination of Total Tannin and 7 Components
Linjin LIANG ; Qi QI ; Ting YE ; Wenyi LIANG ; Ping JIAN ; Kun ZHOU ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(9):1638-1644
The spectrophotometric method was established for the determination of total tannin content in gardenia medicinal materials and tannins, and HPLC method was applied to simultaneously determine gallic acid, punical glucoside A, methyl gallate, punny glucoside B, corilagin, pentagalloyl glucose and the content of ellagic acid. Taking gallic acid as a reference substance, a phosphomolybdate tungstic acid colorimetric method (Pharmacopoeia method) was used to determine the total tannin content. With the chromatographic column Agilent ZORBAX SB-Aq-C18 (250 × 4.6 mm, 5 microns), mobile phase for phosphoric acid (0.1%), methanol, water flow rate of 1 ml/min, column temperature 30℃, detection wavelength of 270 nm, gradient elution, 7 kinds of component contents in myrobalan medicinal materials were measured at the same time. The result showed that the average content of total tannins of Radix Scutellariae was 30.31%, RSD was 0.55%; the average recovery rate was 99.70%, and the RSD was 21.97% (n = 6) . In the scorpion medicinal materials, gallic acid, punical glucoside A, punny glucoside B, methyl gallate, punny glucoside B, creatin, pentagalloglucose and ellagic acid have a good linear relationship in their respective ranges. The recovery rate of the sample is between100.10% and 102.77%. The establishment of the determination method of total tannin, gallic acid, punical glucoside, methyl gallate, corridain, pentagalloglucose and ellagic acid in the scorpion medicinal materials is simple and accurate, which has strong specificity and can be used for quality control of Terminalia chebular.
8.Study on HPLC Fingerprint of Terminalia chebular Retz Based on Chemometrics Analysis
Wenyi LIANG ; Qi QI ; Linjin LIANG ; Ting YE ; Kun ZHOU ; Ping JIAN ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(9):1645-1649
This paper was aimed to establish the HPLC fingerprint of Terminalia chebular Retz The analysis was performed on Agilent ZORBAX SB-Aq C18 column (4.6×250 mm, 5 μm) . The mobile phase was 0.1% phosphate watermethanol solution with gradient elution. The flow rate was 1 mL·min-1. The temperature was maintained at 35℃. The detection wavelength was 270 nm. The injection volume was 20 μL. The chromatographic data of 10 samples was analyzed by similarity of chromatographic data, SPSS software and SIMCA software. The results showed that there were17 common peaks in the diagram. The similarity of 10 samples was between 0.984 and 0.999, which showed that there was no significant difference among these chemical components. The samples were classified into four types according to cluster analysis, which shared the similar results as the principal components analysis (PCA) and partial least sq uares analysis (PLS-DA) . VIP analysis result showed that peak 5 (methyl gallate), 11 and 1 (gallic acid), 10, 12 may be the main chromatographic peaks to identify the samples. It was concluded that chemometrics analysis could be used to analyze, find and distinguish the marker ingredients of Terminalia chebular Retz. This method was accurate and stable, which can provide a reference for the quality control and evaluation of Terminalia chebular Retz.
9.Quality Evaluation of Terminalia billerica (Gaertn.) Roxb.Tannins Fraction from Different Habitats by HPLC Fingerprint Based on HPLC-MSn and Chemometrics
Wenjing CHEN ; Wenyi LIANG ; Shi LI ; Lingfang WU ; Yaping CUI ; Qi QI ; Ting YE ; Linjin LIANG ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(7):1228-1233
This paper was aimed to establish the HPLC fingerprint of T.Billerica (Gaertn.) Roxb.tannin fraction.The analysis was performed on Atlantic T3 (250 mm × 4.6 mm,5 μm) C18 column.The mobile phase was acetonitrile-0.2% glacial acetic acid aqueous solution with gradient elution.The flow rate was 1.0 mL·min-1.The injection size was 20 μL.The temperature was maintained at 30℃.Eleven batches of T.Billerica (Gaertn.) Roxb.tannin fraction of chromatographic data was analyzed by similarity of chromatographic data,SPSS software and SIMCA software.There were 20 common peaks in the diagram.The similarity analysis of 11 samples revealed that the similarities were between 0.832 and 0.973.Only the similarity of tannin parts from Xinjiang was below 0.9.The cluster analysis classified the tannin parts into 3 types,which shared the similar results as the principal components analysis (PCA).PLS-DA found that peak 1,13 and 14 may be the main chromatographic peaks to identify tannins fraction.The HPLC-MSn information of 14 compounds in T.billerica (Gaertn.) Roxb.was summarized.It was concluded that chemometrics analysis method can be used to analyze the HPLC fingerprint of T.billerica (Gaertn.) Roxb.tannin fraction.This method was rapid,simple,and reproducible.It can be used as one of the effective methods for the quality control of T.billerica (Gaertn.) Roxb.tannin fraction.
10.Research on Stability of Tannin Part in Phyllanthus Emblica L.in Artificial Gastric And Intestinal Juice
Lingfang WU ; Ting YE ; Linjin LIANG ; Wenyi LIANG ; Wenjing CHEN ; Shi LI ; Yaping CUI ; Qi QI ; Lanzhen ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(8):1386-1390
This article was aimed to study the stability of tannin parts in Phyllanthus emblica L.in artificial gastric and intestinal juice,in order to provide a foundation for in vivo studies of Phyllanthus emblica L.HPLC-UV was used to determine the contents of main ingredients.The results showed that stability of main ingredients of tannin parts in Phyllanthus emblica L.,including gallic acid (GA),corilagin and ellagic acid (EA),in the artificial gastric juice.The content change was not obvious.The residual content was within 100%.The half-life was above 90 h.They were unstable in the artificial intestinal juice.The content was first increased and then decreased.The residual content was 100-300%.The half-life was above 10 h.It was concluded that the tannin parts in Phyllanthus emblica L.was stable in artificial gastric juice.And content changes of main components were not obvious.The tannin parts in Phyllanthus emblica L.were unstable in artificial intestinal juice.The main ingredients were first increased and then decreased.It was speculated that macromolecule can hydrolyze tannin part into small molecules.Hnwever,as time increases,all components may be decomposed.

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