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Objective:To explore the potential targets and mechanism of action of "Clematis Radix et Rhizoma-Trichosanthis Radix" based on network pharmacology. Method:Chinese Medicine System Pharmacology Analysis Platform（TCMSP） was used to screen out active ingredients and corresponding target proteins of Clematis Radix et Rhizoma and Trichosanthis Radix according to oral bioavailability（OB） and drug likeness（DL），cancer disease targets were screened out using GeneCards and OMIM databases，R language software was used to screen out common targets of clematis，trichosanthin and cancer diseases， Cytoscape 3.7.2 software was used to construct a network map of "drug-active ingredient-disease-target"， STRING database was used to draw protein protein interaction（PPI）of common target proteins， R language software was used to perform enrichment analysis of gene ontology（GO） functions and Kyoto encyclopedia of genes and genomes（KEGG） channels on effective targets. Result:A total of 9 effective active ingredients were obtained from Clematis Radix et Rhizoma-Trichosanthis Radix powder pair. A total of 31 target genes were searched，and 814 relevant target genes were searched from cancer diseases. The two kinds of relevant target genes were matched to obtain 9 common target genes，which mainly involved endopeptidase，cysteine-type endopeptidase activities involving in the apoptosis process and cancer necrosis factor receptor superfamily binding and other biological processes，and played a role in the treatment of cancers by regulating apoptosis，measles，hepatitis B，kaposi sarcoma-associated herpesvirus infection，p53，interleukin-17（IL-17），tumor necrosis factor（TNF） and many other pathways. Conclusion:The mechanism of Clematis Radix et Rhizoma-Trichosanthis Radix in the treatment of cancer is preliminarily studied. Clematis Radix et Rhizoma-Trichosanthis Radix has multiple active ingredients and can play a role in treating cancer through multiple targets and multiple pathways.
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Objective:The Meta-analysis was used to systematically evaluate the clinical efficacy of traditional Chinese medicine in treating Late onset hyponatremia （late onset hyponatremia，LOH）. Method:Pubmed，Web of Science，China Knowledge Base Database （CNKI），Wanfang Database （WanFang），Weipu Full-text Periodical Database（VIP），Chinese Biomedical Literature Database （CBM）were retrieved to collect randomized controlled trials of traditional Chinese medicine（TCM） for treatment of LOH. Two researchers independently screened out the literatures， extracted the data， conducted quality assessment by Cochrance bias risk assessment tool，and made Meta-analysis by RevMan 5.3.5 software. Result:Nine eligible documents were finally included. Meta-analysis results showed that the test group was superior to the control group in improving patient's physical fitness/cardiovascular score ［mean deviation（MD）=-1.42，95% CI（-2.39，-0.45），<italic>P</italic>=0.004］ and psycho-psychological score［MD=-0.74，95% CI（-1.26，-0.22），<italic>P</italic>=0.005］，with no statistically significant difference between test group and control group in sexual function score ［MD=-0.68，95% CI（-1.38，-0.03），<italic>P</italic>=0.06］，serum testosterone （TT） concentration［MD=-0.68，95% CI（-1.38，-0.03），<italic>P</italic>=0.06］ and effective rate ［odds ratio（OR）=1.57，95% CI（0.64，3.88），<italic>P</italic>=0.33］. Conclusion:TCM is equivalent to western medicine（testosterone undecanoate）in the treatment of late onset hypogonadism， and better than western medicine in improving patients' physical fitness/cardiovascular score and mental and psychological score.
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Objective:To explore the therapeutic principles and medication regularity of Chinese medicine for the treatment of urolithiasis based on data mining and literature research. Method:Chinese National Knowledge Infrastructure（CNKI） was searched for the clinical research papers on Chinese medicinal compounds for the treatment of urolithiasis published from database inception to November 10，2020. Therapeutic methods and Chinese medicinal compounds were extracted from the included papers，and the frequencies of therapeutic methods and the drugs in the Chinese medicinal compounds，as well as the efficacies were analyzed. The medication regularity of high-frequency drugs was explored by association rule analysis and cluster analysis. Result:A total of 247 papers and 247 Chinese medicinal compounds were included，and 209 drugs were involved. Those with high frequencies included Lysimachiae Herba，Galli Gigerii Endothelium Corneum，Lygodii Spora，Achyranthis Bidentatae Radix，Pyrrosiae Folium，Plantaginis Semen，and Talcum. The drugs with the highest frequency were effective in promoting urination，draining dampness，and activating blood to resolve stasis，followed by those in tonifying deficiency，regulating Qi，and purgation. Galli Gigerii Endothelium Corneum，Clematidis Radix et Rhizoma，and Succinum were used as specialized drugs targeting the syndrome. Association rule analysis showed that Lysimachiae Herba，Galli Gigerii Endothelium Corneum，and Lygodii Spora were commonly used in pairwise or ternary combination，followed by the pairwise combinations of Lysimachiae Herba with Achyranthis Bidentatae Radix，Pyrrosiae Folium，and Plantaginis Semen. High-frequency drugs were clustered into four categories by clustering analysis. Thirty-one therapeutic principles were employed in the 247 Chinese medicinal compounds. The ones with the highest frequency were clearing heat and eliminating dampness，resolving stasis and promoting urination，and tonifying kidney and replenishing qi. Conclusion:For the treatment of urolithiasis，promoting urination and draining dampness is the core therapeutic principle，and activating blood to resolve stasis is the important therapeutic principle，while tonifying is the potential therapeutic principle. The medication for urolithiasis is featured by specialized drugs targeting the syndrome.
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Objective:Exploring the material basis and mechanism of Wuzi Yanzongwan in the treatment of male infertility based on network pharmacology. Method:Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active ingredients and targets in Wuzi Yanzongwan. GeneCards, OMIM and PharmGkb databases were used to screen the targets of male infertility. R language software was used to screen common targets of drugs and diseases, Pharmaceutical active ingredients-disease target interaction network was constructed by using Cytoscape software. The common target protein interaction network (PPI) was constructed by STRING platform, the gene ontology(GO) analysis of common target was analyzed by ClueGo plug-in, and Kyoto encyclopedia of genes and genomes(KEGG) pathway was enriched by R language software. Result:A total of 72 active ingredients were obtained from Wuzi Yanzongwan, and 35 possible targets for the treatment of male infertility were obtained. These targets are mainly involved in biological processes such as oxidation and antioxidant activity, and are mainly concentrated in phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) and hypoxia inducible factor-1(HIF-1) signaling pathways. Conclusion:The network pharmacology confirmed the multi-component, multi-target and multi-pathway action characteristics of Wuzi Yanzongwan, predicted the possible mechanism of Wuzi Yanzongwan in the treatment of male infertility, and provided theoretical basis for further study of its active ingredients and mechanism.
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<p><b>OBJECTIVE</b>To examine the extent of hypoxia in oral squamous cell carcinoma and investigate the factors related to the hypoxia.</p><p><b>METHODS</b>An animal model of oral squamous cell carcinoma was established and single photon emission computed tomography (SPECT) with 99mTc-HL91 used to detect the hypoxia extent of the oral squamous cell carcinoma. The expression of hypoxia inducible factor 1 alpha (HIF-1alpha) was examined by immunohistochemical staining in 42 cases of formalin-fixed paraffin-embed squamous cell carcinoma.</p><p><b>RESULTS</b>The uptake of 99mTc-HL91 in the tumor tissue was higher than that in normal tissue and had linear relation with the tumor size (P < 0.05). There was no HIF-1alpha expression in the normal oral mucosa. The expression of HIF-1alpha was high in oral mucosa carcinoma and closely related to the differentiation degree of tumor and metastasis of lymph node (P < 0.05).</p><p><b>CONCLUSIONS</b>Tumor tissue had broad hypoxic region. HIF-1alpha highly expressed in oral squamous cell carcinoma and may play an important role in carcinogenesis and aggression.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Animals , Female , Humans , Male , Mice , Middle Aged , Carcinoma, Squamous Cell , Diagnostic Imaging , Metabolism , Pathology , Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Mice, Inbred BALB C , Mice, Nude , Mouth Neoplasms , Diagnostic Imaging , Metabolism , Pathology , Pilot Projects , Tomography, Emission-Computed, Single-Photon , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression and significance of integrin-beta1 in oral leukoplakia and early invasive carcinoma.</p><p><b>METHODS</b>The expression of integrin-beta1 and Ki-67 was examined in 12 normal oral mucosa, 10 simple hyperplasia, 24 epithelial dysplasia and 14 early invasive carcinoma by immunohistochemistry.</p><p><b>RESULTS</b>In normal and simple hyperplasia epithelium, integrin-beta1 was mostly expressed in the basal cell membrane, and Ki-67 in the nuclei of basal and the parabasal layers. In dysplasia epithelium and early invasive carcinoma, integrin-beta1 showed membrane staining and Ki-67 showed nuclear staining in dysplastic basal cells, sprinkle cells and SCC cells. Integrin-beta1 and Ki-67 were overexpressed in 7 and 10 of 24 dysplasia cases and in 8 of 14 early invasive carcinoma cases respectively. There was a significant difference in integrin-beta1 and Ki-67 expression among the four groups (chi2 = 10.651, P = 0.014; chi2 = 14.831, P = 0.002), in integrin-beta1 expression among normal oral mucosa, simple hyperplasia and early invasive carcinoma (P = 0.008, P = 0.013) and in Ki-67 expression among normal oral mucosa and dysplasia, early invasive carcinoma (P = 0.026, P = 0.001), and among simple hyperplasia and early invasive carcinoma (P = 0.005). A significant correlation between integrin-beta1 and Ki-67 (R = 0.442, P < 0.01) was found.</p><p><b>CONCLUSIONS</b>Integrin-beta1 showed increased staining in dysplasia epithelium cells and SCC cells, and may correlate to the proliferation of the dysplasia cells.</p>