Effect of Gualou Xiebai Decoction on pulmonary fibrosis in rats based on pyroptosis pathway / 中国中药杂志

This study investigated the effect of Gualou Xiebai Decoction on rats with bleomycin-induced pulmonary fibrosis. The rats were randomly divided into a control group, a model group, a low-dose Gualou Xiebai Decoction group(2.4 g·kg~(-1)), a high-dose Gualou Xiebai Decoction group(4.8 g·kg~(-1)), and pirfenidone group(150 mg·kg~(-1)). The model of pulmonary fibrosis was established by intratracheal instillation of bleomycin in all groups, except the control group. Since the second day of modeling, the corresponding drugs were given to rats by intragastric administration, once a day for 14 d and 28 d. The hematoxylin-eosin(HE) staining was used to evaluate the degree of inflammatory injury in lung tissues. The immunofluorescence staining was used to detect the expression of CD68 and CD163 in lung tissues of rats. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in serum and brochoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). The expression of pyroptosis-related genes in lung tissues of rats was detected by qRT-PCR. The results of HE staining and immunofluorescence staining showed that the lung tissue structure was normal in the control group. In addition, there were alveolar collapse or even closure in lung tissues of rats in the model group, with obvious inflammatory cell infiltration, and the expression of CD68 and CD163 was significantly up-regulated. As compared with the model group, the lung tissue structure of rats in the Gualou Xiebai Decoction groups was significantly improved, with alleviated inflammation, and the expression of CD68 and CD163 was decreased. As compared with the control group, the level of TNF-α in serum and BALF of rats in the model group was significantly increased(P<0.01), the mRNA expression levels of alpha smooth muscle actin(α-SMA), collagen type Ⅰ alpha 1 chain(Col1a1), caspase-1, IL-1β, IL-18, gasdermin D(Gsdmd), and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in lung tissues were significantly increased(P<0.05, P<0.01), and the mRNA expression level of E-cadherin was significantly decreased(P<0.01). As compared with the model group, the level of TNF-α in serum and BALF was significantly down-regulated in the high-dose Gualou Xiebai Decoction group(P<0.05, P<0.01), and that of IL-10 was up-regulated(P<0.05, P<0.01). The mRNA expression levels of α-SMA, Col1a1, caspase-1, IL-18, Gsdmd, NLRP3 and IL-1β in lung tissues were significantly decreased(P<0.05, P<0.01) in the high-dose Gualou Xiebai Decoction group, and the mRNA expression level of E-cadherin was significantly increased(P<0.05, P<0.01). In conclusion, Gualou Xiebai Decoction can down-regulate the levels of inflammatory factors and related genes and effectively mitigate pulmonary fibrosis by regulating the pyroptosis pathways.

Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics / 中国中药杂志

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Mechanism of Liu Junzitang in Treatment of Muscle Atrophy in Mice with Lung Cancer Cachexia Through Regulating STAT3/Ubiquitin Proteasome Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3（STAT3）/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group， a model group， a Liu Junzitang group， an inhibitor group （stattic group），and a Liu Junzitang + inhibitor group （combination group）， with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation， the mice in the corresponding groups received Liu Junzitang （9.56 g·kg-1·d-1） by gavage and intraperitoneal injection of stattic ［25 mg·kg-1·（2 d）-1］. After three weeks of drug intervention， the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin （HE） staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 （p-STAT3）， STAT3， muscle atrophy F-box （MAFbx）， and muscle RING finger protein 1 （MuRF1） in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT3， MAFbx， and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group， the model group showed lightened body and the gastrocnemius muscle， reduced cross-sectional area of gastrocnemius muscle fibers， and increased protein expression of p-STAT3， STAT3， MAFbx， and MuRF1 and mRNA expression of STAT3， MuRF1， and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the model group， the Liu Junzitang group showed increased body weight， gastrocnemius muscle weight， and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and decreased protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and reduced protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the combination group showed increased body weight and gastrocnemius muscle weight （P<0.05），and decreased protein expression of p-STAT3， STAT3， MuRF1， and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the Liu Junzitang group， the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle （P<0.05）. ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia， and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.

Polysaccharide of Atractylodis Macrocephalae Rhizoma inhibits expression of immune checkpoint PD-L1 by targeting miR-34a in esophageal carcinoma cells / 中国中药杂志

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.

Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments / 中国中药杂志

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Neuronal Autophagy in Depression and Regulatory Effect of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Depression is a mental illness characterized by persistent negative feelings， which has seriously threatened people's health. In recent years， neuronal autophagy， an important stress response， has also been regarded as a hypothesis for the pathogenesis of depression. Relevant studies have shown that either insufficient or excessive autophagy triggers neuronal damage， and activated or inhibited neuronal autophagy can be observed in animal models of depression. Therefore， neuronal autophagy may be a double-edged sword involved in the pathogenesis of depression. It is believed in traditional Chinese medicine （TCM） that the occurrence of this disease is closely related to liver depression and spleen deficiency. Chinese medicine regulates the neuronal autophagy via multiple ways. The TCM monomers that regulate neuron autophagy are capable of protecting nerves or penetrating the blood-brain barrier. TCM compounds designed for soothing liver or invigorating spleen have been proved effective against this disease， demonstrating that the core pathogenesis of depression lies in liver depression and spleen deficiency. The regulatory effects of TCM on neuronal autophagy in depression models might result from its action on multiple targets， multiple pathways， and multiple systems. This paper discussed the limitations in current research based on the involvement of neuronal autophagy in depression and its treatments， in order to provide ideas for later similar research and that concerning TCM treatment of depression.

Identification and Expression Analysis of TIFY Transcription Factor in Eucommia ulmoides / 中国实验方剂学杂志

Objective:To identify the TIFY gene family in <italic>Eucommia ulmoides</italic> and analyze its expression from the whole genome level to lay the foundation for further study on <italic>EuTIFYs</italic> gene function. Method:Based on the <italic>E. ulmoides</italic> genome database，the TIFY gene family was identified through bioinformatics analysis tools such as National Center for Biotechnology Information（NCBI），MEME，PlantCare，Expert Protein Analysis System（ExPASy），and TBtools. Physicochemical properties，phylogenetic evolution，gene structure，<italic>cis</italic>-acting elements of the promoters and their expression patterns in leaf development and gum formation of the gene family were systematically analyzed. Result:In this study，fourteen <italic>EuTIFY</italic> genes （<italic>EuTIFY1</italic>-<italic>EuTIFY14</italic>） were identified in the <italic>E. ulmoides</italic> genome. The <italic>EuTIFYs</italic> were composed of 312-1 074 bp nucleotides encoding 102-357 amino acid residues，with isoelectric points of 4.99-10.06 and molecular weight in the range of 10.8-39.14 kDa. According to putative subcellular localization，proteins，which were mainly hydrophilic proteins，localized in the nucleus. The 14 <italic>EuTIFYs</italic> were unevenly distributed on 13 chromosomes. <italic>EuTIFY</italic> gene family was divided into four subfamilies： <italic>TIFY</italic>，<italic>JAZ</italic>，<italic>ZML</italic>，and <italic>PPD</italic>，which contained three，four，five，and two members respectively. The promoters of <italic>EuTIFYs</italic> contained multiple photoperiodic and abiotic stress-responsive cis-acting elements，which were involved in plant growth and abiotic stress regulation. Expression pattern analysis showed that <italic>EuTIFYs </italic>exhibited different expression levels in different development stages of <italic>E. ulmoides</italic> leaves and multiple interactions，and most of the genes were highly expressed in the early stage of leaf development and positively regulated the formation of <italic>E. ulmoides</italic> gum. Conclusion:Fourteen <italic>EuTIFYs</italic> were identified from the whole genome of <italic>E. ulmoides</italic>，and their structural characteristics and expression patterns were analyzed by bioinformatics. The findings of this study are expected to provide references for further research on the function of <italic>EuTIFYs</italic>.

Discussion on Pathogenesis of Tumor Based on Theory of Exogenous Pathogenic Factors / 中国实验方剂学杂志

With the emerging cases of tumor is about to exceed 4 million per year in China， tumor prevention and control is also a formidable barrier hitting the world. Overall， an increasing trend of incidence and mortality of tumor in China has been observed in recent years， and the high mortality and low cure rate of tumor have seriously threaten the health of Chinese people， greatly affected the quality of life of patients， greatly reduced the living standard of patients and endangered the physical and mental health of patients. Traditional Chinese medicine（TCM） believes that the etiology of tumor is complex and pathogenesis is variable， which is the result of interaction between internal and external factors. If the treatment is carried out based on syndrome differentiation in time at the beginning when exogenous pathogens act on the human body， so as to prevent the spread of latent pathogen in human body， the occurrence and development of tumor diseases will be significantly reduced. Therefore， the theory of exogenous pathogenic factors and the pathogenesis of tumor need to be further explored. A total of 67 Chinese and English literatures were searched out with key words like external contraction， pathogenic Qi， TCM， tumor and pathogenesis in China National Knowledge Infrastructure （CNKI） and Public Medline （PubMed） databases for reference， so as to discuss the theory of exogenous pathogens and the pathogenesis of tumor comprehensively. The important role of exogenous pathogens in tumor pathogenesis and the significance of TCM in the early prevention and treatment of tumors were emphasized. Exogenous pathogenic factors such as wind， cold， dampness， fire， natural and social factors， diet and living conditions lead to the complexity of the occurrence of tumors. TCM can effectively prevent and intervene in the early stage of tumor onset， contribute to disease prevention and tumor resistance， reduce the occurrence， development and transformation of tumors， and make the clinical medication more effective， more accurate and more targeted， so as not to miss the opportunity for treating tumor， and provide a more clear guidance for clinical treatment of tumors.

Effect of Qigesan on Proliferation， Apoptosis and miR-133a/Akt/mTOR Signaling Pathway of Esophageal Cancer EC9706 Cells / 中国实验方剂学杂志

Objective:To observe the effect of Qigesan on the proliferation and apoptosis of the human esophageal cancer cell EC9706， and the effect on miR-133a/protein kinase B（Akt）/mammalian target of rapamycin （mTOR） signaling pathway. Method:The effective constituent of Qigesan was extracted by ethyl acetate. Thiazolyl blue tetrazolium bromide（MTT） colorimetric assay was used to determine the dosage of Qigesan on cells and to detect the effect of Qigesan on the proliferation of EC9706 cells. The effect of Qigesan on apoptosis of EC9706 cells was detected by flow cytometry. The effect of Qigesan on miR-133a and insulin-like growth factor 1 receptor（IGF-1R） mRNA expression was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） . The protein expression of Akt and mTOR in EC9706 cells was detected by Western blot. Result:Qigesan can inhibit the proliferation of EC9706 cells in a dose-dependent manner（<italic>P</italic><0.01）. Inhibitory concentrations 30% inhibition concentration（IC₃₀） 40 mg·L^-1 and median inhibition concentration（IC₅₀） 80 mg·L^-1 were selected for follow-up experiments. Compared with the blank group， both the inhibitor group and the combination drug group can inhibit the proliferation of EC9706 cells （<italic>P</italic><0.01）. The inhibitor at 0.25 μmol·L^-1 was selected for subsequent experiments. Compared with the blank group， Qigesan 80 mg·L^-1 dose group could significantly promote the late apoptosis rate and total apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， and the 40 mg·L^-1 dose group could significantly promote the late apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， which shows synergistic effect after concomitant use with Akt/mTOR inhibitor（<italic>P</italic><0.05）. Compared with the blank control group， each group can effectively increase expression of miR-133a（<italic>P</italic><0.05）. The combination of inhibitor and traditional Chinese medicine（TCM） has obvious promotion effect. Compared with blank control group， the expressions of Akt and mTOR were significantly decreased in each group（<italic>P</italic><0.05）. Compared with single medication， the expressions of Akt and mTOR were decreased in combination of inhibitor and TCM group. Conclusion:Qigesan can inhibit the growth of EC9706 cells and promote apoptosis， and its inhibitory mechanism may be related to the Akt/mTOR signaling pathway by regulating the expression of miR-133a.

Study Progress in Pathogenesis of Cancer Cachexia and Prevention and Treatment with Traditional Chinese Medicine / 中国实验方剂学杂志

Objective:The incidence rate of cancer cachexia is high in late stage of cancer， which is characterized by skeletal muscle atrophy and rapid reduction of adipose tissue and systemic inflammation. Cachexia is highly related to a variety of tumors， and causes a large proportion of cancer deaths. Cancer cachexia can lead to serious complications in patients with cancer， then， the quality of life of patients decreases， the psychological state becomes negative， and the state of illness is further worsened. At present， there is no effective intervention means to completely reverse cachexia. The combined use of multiple targets and effective components of traditional Chinese medicine（TCM）， as well as the treatment based on syndrome differentiation and the theory of TCM play an important role in the prevention and treatment of cancer cachexia. Therefore， exploring the pathogenesis of cancer cachexia and prevention and treatment with TCM is helpful for basic study and clinical application. Method:In this paper， cancer cachexia and TCM in China national knowledge infrastructure （CNKI） and Public Medline （PubMed） databases were retrieved， and 98 Chinese and English literatures were included through summarization to elaborate the pathogenesis of cancer cachexia and the prevention and treatment of TCM. Result:Emphasis was given to the important role of inflammatory reaction， skeletal muscle atrophy， energy metabolism abnormality and multiple signal joint regulation in occurrence of cancer cachexia， and the unique advantages and significant role of TCM in treatment of cancer cachexia under different treatment principles. Conclusion:Inflammatory reaction， skeletal muscle atrophy， abnormal energy metabolism make the pathogenesis of cancer cachexia complex and diverse. TCM prescriptions， Chinese herbal medicine and their effective ingredients have the natural advantages of targeting multiple pathways， controlling multiple signal pathways and inhibiting various inflammatory factors in the prevention and treatment of cancer cachexia， and are safe and effective in improving diet， prolonging the survival period of patients and keeping weight.

Mechanism of PI3K/Akt Signaling Pathway in Affecting Growth of Esophageal Cancer Cell and Research Progress of Intervention of Traditional Chinese Medicine / 中国实验方剂学杂志

Esophageal cancer is one of the malignant tumors with a high morbidity and mortality in China. According to China's latest cancer report released by the National Cancer Center in 2019, the number of people suffering from esophageal cancer reached 246 000 in 2015, and the death toll reached 188 000. How to effectively treat esophageal cancer and improve the survival rate of patients is one of the most urgent problems in the field of medicine. Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most important signaling pathway for regulating cell survival, differentiation and apoptosis in the body. It also plays an important role in the occurrence and mechanism of various cancers. Recent studies have shown that the activation of PI3K/Akt signaling pathway is an important factor in regulating proliferation, apoptosis, cycle arrest, migration and invasion of esophageal cancer cells. The long-term clinical observation found that traditional Chinese medicine has a stable effect in the treatment of esophageal cancer and little side effects, especially in improving the quality of life of cancer patients and prolonging the survival period of patients. At present, it is a research hotspot to intervene this signal pathway with traditional Chinese medicine in the treatment of esophageal cancer, so as to explore its mechanism of action on esophageal cancer. This paper focused on literatures in CNKI and PubMed databases from 2009 to 2019, with PI3K/Akt signaling pathway, esophageal cancer and miRNA as the key words. A total of 226 literatures were retrieved, and 61 literatures relating to traditional Chinese medicine, esophageal cancer, miRNA and PI3K/Akt signaling pathway were sorted out and summarized. This paper reviewed the mechanism of PI3K/Akt signaling pathway in esophageal cancer, the relationship between miRNA and PI3K/Akt signaling pathway and esophageal cancer, and how traditional Chinese medicine can regulate the expressions of relevant proteins in PI3K/Akt signaling pathway to inhibit cell proliferation, affect cell growth cycle, induce cell apoptosis, inducing cell autophagy, inhibit tumor invasion and metastasis, inhibit angiogenesis. Finally, it can improve esophageal cancer to provide theoretical basis and scientific basis for the treatment of esophageal cancer with traditional Chinese medicine.

Inhibition of CaMKII alleviates myocardial ischemia?reperfusion injury by reducing mitochondrial oxidative stress in isolated perfused rat heart / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in myocardial ischemia-reperfusion (IR) injury in isolated perfused rat heart and explore the underlying mechanisms.</p><p><b>METHODS</b>An ischemia-reperfusion (IR) model was prepared using isolated rat hearts perfused with Krebs-Henseleit solution were randomly divided into control group, 2.5 µmol/L KN-93 group, IR (induced by ischemia for 45 min followed by reperfusion for 120 min) group and KN-93+IR group. The myocardial performance was evaluated by assessing the left ventricular pressure. Lactate dehydrogenase (LDH) activity and cTnI content in the coronary flow and the infarct size were determined to evaluate the myocardial injury. The phosphorylation of CaMKII (p-CaMKII) and PLN (p-PLN) and oxidation of CaMKII (ox--CaMKII) were measured with Western blotting. The activity of mitochondrial superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using ELISA.</p><p><b>RESULTS</b>Compared with the control group, KN-93 treatment at 2.5 µmol/L produced no significant effects on cardiac function or performance in rat hearts without IR injury. Myocardial IR injury significantly decreased myocardial performance and mitochondrial SOD activity in the perfused hearts (P<0.01) and caused significantly increased infarct size, LDH activity, cTnI content, expressions of p-CaMKII, ox-CaMKII and p-PLN, and also increased mitochondrial MDA content (P<0.01). KN-93 treatment at 2.5 µmol/L administered before ischemia and before reperfusion markedly attenuated such changes induced by ischemia and reperfusion (P<0.01).</p><p><b>CONCLUSION</b>CaMKII participates in myocardial IR injury in isolated rat heart, and inhibiting CaMKII can alleviate myocardial injury by relieving mitochondrial oxidation stress.</p>

Effects of pargyline on histone methylation in promoter and enhancer regions and transcription of CYP3A4/3A7 / 药学学报

This study was designed to investigate effects of pargyline on histone methylation in the promoter and enhancer regions and transcription of cytochrome P450 3A4/3A7 (CYP3A4/3A7) gene. Human primary fetal liver cells were isolated, cultured and randomly divided into several groups including control, solvent, pargyline low, middle, high dose (treated with 0.6, 1.2, 2.4 mmol·L-1). HepG2 cells were cultured and treated with 0.03, 0.3, 3 mmol·L-1 pargyline. After 48 hours, total RNAs were prepared from the cells to determine the expression of CYP3A mRNA in primary fetal cells and HepG2 cells with real-time quantative PCR (qPCR). HepG2 cells were cultured and then treated with 3 mmol·L-1 pargyline for 48 hours. The chromatin immunoprecipitation (ChIP) assay was performed with dimethylation of histone H3 at lysine 4 (H3K4me2), and IgG antibodies respectively. The precipitated DNA was resuspended and used for qPCR. Primers were used to detect different regions of CYP3A4/3A7 promoter and enhancer. Occupancy of H3K4me2 was shown as percent of input DNA relative to control cells. The results suggested that pargyline has an effect on primary fetal liver cells and HepG2 cells proliferation. The level of CYP3A7 was markedly enhanced in human primary fetal liver cells by treatment with 1.2, 2.4 mmol·L-1 of pargyline (P-1 of pargyline in HepG2 cells (P<0.001) compared with solvent control. Occupancy of H3K4me2 on human CYP3A4 promoter (-362 to +53) and enhancer segment (-7 836 to -6 093) harbored the overlapping hepatocyte nuclear factors 4A (HNF4A) binding site compared with a negative control. Occupancy of H3K4me2 on human CYP3A7 promoter (-163 to +103) and enhancer segment (-4 054 to -3 421, -6 265 to -6 247) overlapped with glucocorticoid receptor (GR) binding site. In conclusion, the enriched H3K4me2 in the promoter and enhancer regions was induced by pargyline with HNF4A or GR binding site in CYP3A4/3A7 gene to activate the corresponding genes.

Discussion of Chinese medical research ideas from miRNAs features / 中国中西医结合杂志

In this paper, miRNAs features were briefly introduced and agreeable points were discussed from 4 aspects: organs relationship, syndrome research, Chinese medical pathogeneses, and actions of Chinese herbs. miRNAs, as information media for organs interrelation, was believed to explain Chinese medical pathogeneses and reveal partial molecular mechanisms of Chinese medicine. miRNAs in the body fluid could be taken as one of biological bases of syndromes.

Post-Traumatic Cerebral Infarction Following Low-Energy Penetrating Craniocerebral Injury Caused by a Nail

Post-traumatic cerebral infarction (PTCI) is a secondary insult which causes global cerebral hypoxia or hypoperfusion after traumatic brain injury, and carries a remarkable high mortality rate. PTCI is usually caused by blunt brain injury with gross hematoma and/or brain herniation. Herein, we present the case of a 91-year-old male who had sustained PTCI following a low-energy penetrating craniocerebral injury due to a nail without evidence of hematoma. The patient survived after a decompressive craniectomy, but permanent neurological damage occurred. This is the first case of profound PTCI following a low-energy penetrating craniocerebral nail injury and reminds clinicians of possibility this rare dreadful complication for care of head-injured patients.

Study on ribosomal protein gene expression in patients with ulcerative colitis of Pi-asthenic syndrome and Pi-asthenic syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study differential expression profiles of ribosomal protein (RP) genes in healthy subjects and ulcerative colitis (UC) patients of Pi-asthenic syndrome (PAS) and of dampness-heat syndrome (DHS), thus providing experimental bases for " Pi as the source of qi and blood" theory from the view of protein synthesis.</p><p><b>METHODS</b>RP genes arrays were made. The mucous membrane of colon was detected in four UC patients of PAS (UC-PAS), four UC patients of DHS (UC-DHS), and four healthy subjects (N), and data analyzed using BRB-TOOL Software Package (3.9). Bioinformatics analyses were conducted in differential genes.</p><p><b>RESULTS</b>Low-density RP gene chips were successfully produced, including 77 RP genes and two RP like genes (RPL26-like1 and RPL7-like1). There were twelve differential genes between UC (PAS+DHS) and N, all of which were down-regulated genes. There were nineteen differential genes between UC-DHS and N, all of which showed down-regulating tendency. There were three differential genes between UC-PAS and N, all of which were down-regulated genes. There were six differential genes between UC-PAS and UC-DHS, all of which were up-regulated genes. Cluster analysis showed that normal and UC samples of this chip can be classified according to gene expression profiles, and UC-PAS and UC-DHS can be classified by clustering. Various differential genes had a common transcription regulatory factor.</p><p><b>CONCLUSIONS</b>RP genes arrays were successfully produced. RP gene expressions were down-regulated in UC-PAS and UC-DHS. Corresponding gene expression profiles were shown in N, UC-PAS and UC-DHS.</p>

Effect and mechanism of reserpine for changing salivary protein secretion in Pi-deficient rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of reserpine (RSP) for changing salivary protein secretion in Pi-deficient rats and to explore its possible mechanism.</p><p><b>METHODS</b>Twenty rats allocated in the RSP group were given subcutaneous injection of RSP [0.4 mg/(kg x d)] for 9 successive days, while the other 20 rats in the control group were injected with same volume of saline instead. On the 10th day, ten rats randomly selected from each group were subjected for extracting saliva to detect salivary amylase activity (sAA) before and after an acid stimulation; and drawing blood from the orbital vein to measure the contents of vasoactive intestinal peptide (VIP) and cyclic adenosine monophosphate (cAMP). Then they were sacrificed and their parotids were taken out for pathological examination with HE staining, as well as for VIP and cAMP measuring, and zymogen granules counting under a transmission electron microscope. The remainder animals were stopped injecting and normally fed to 40 days, then subjected to be detected as above-mentioned.</p><p><b>RESULTS</b>Food intake and body weight reduction were more significantly in the RSP group than in the control group. On the 10th day, the ratio of sAA before/after stimulation in the RSP group was 0.39 +/- 0.18, significantly lower than that in the control group (0.80 +/- 0.21, P < 0.01), but it was restored rapidly, reaching the normal range on the 25th day, on the 40th day, it became significantly different to the level on the 10th day (P < 0.05) and approached the level in the control group (P > 0.05). No significant pathological change of parotid was found in both groups; but the number of zymogen granules in the RSP group was remarkably more than that in the control group (41.4 +/- 4.9 vs 34.6 +/- 5.2, P < 0.01). Serum level of VIP in the RSP group was significantly less while that of cAMP was higher than that in the control group (22.5 +/- 13.1 mg/L vs 38.5 +/- 14.1 mg/L, and 125.8 +/- 15.5 micromol/L vs 105.3 +/- 16.7 micromol/L, both P < 0.05), but no inter-group difference was found in parotid tissue contents of both VIP and cAMP. All the indices detected became equivalent in the two groups on the 40th day.</p><p><b>CONCLUSION</b>The reduction of salivary protein in Pi-deficient rats induced by RSP may be related to the regulatory pathway of VIP and cAMP.</p>

The Characteristics of Acute Aortic Dissection among Young Chinese Patients: A Comparison between Marfan Syndrome and Non-Marfan Syndrome Patients

PURPOSE: Aortic dissection (AoD) is one of the most common catastrophes involving the aorta. Nevertheless, early diagnosis remains to be a challenge in the Emergency Department (ED), particularly in young individuals. In this study, we attempted to identify the characteristics of acute AoD among young individuals, particular in patients with Marfan syndrome. MATERIALS AND METHODS: This was an retrospective chart-review study conducted in a tertiary referring hospital. The hospital database was queried for the combination of AoD and patients under age of 40 years. The medical charts were reviewed to obtain demographic data, clinical data and laboratory characteristics by using a standardized data collection sheet. A comparison between Marfan syndrome and non-Marfan syndrome patients was performed. RESULTS: During the 10-years period, 18 of 344 patients with acute AoD were younger than 40 years-old. Patients with Marfan syndrome developed acute AoD at a younger age than patients without Marfan syndrome. The mean diastolic blood pressure was significantly lower in patients with Marfan syndrome upon presenting to the ED than those without. Patients with Marfan syndrome had trends toward higher risk of development of type A AoD, increased recurrence rate and higher mortality rate than those without. However, statistical significance was not present. CONCLUSION: ED physicians should have high alert to acute AoD in young patients presenting with severe unexplained chest and back pain, particularly in those patients with a history of heart diseases, hypertension, and Marfan syndrome or featuring Marfanoid habitus. Acute coronary syndrome, unexplained abdominal symptoms, and sudden cardiac arrest could be the initial manifestation of AoD in young patients. A low threshold to perform enhanced computed tomography may facilitate early diagnosis and timely treatment in this patient population.

Bioinformatics research on chronic superficial gastritis of Pi-deficiency syndrome by gene arrays / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the bioinformatical characteristics of differential gene expression in patients with chronic superficial gastritis (CSG) with the Pi-deficiency syndrome (PDS) and those of the non-Pi-deficiency syndrome (non-PDS), i.e. patients of CSG with Pi-Wei dampnese-heat syndrome and healthy persons.</p><p><b>METHODS</b>With the BRB-Array Tools software package, original data collection and bioinformatic: analysis of gene arrays were conducted in 6 CSG patients of PDS (CSG-PDS), 6 CSG patients of non-PDS (CSG-nPDS), and 6 healthy volunteers (Normal).</p><p><b>RESULTS</b>Compared with non-PDS, the gene expressions: in PDS with regards to protein synthesis, energy metabolism, immune reaction and ionic transport tended to be down-regulated, while those concerning secretion, cytoskeleton and ubiquitinization were up-regulated dominantly.</p><p><b>CONCLUSIONS</b>The two kinds of samples, CSG-PDS/Normal and CSG-PDS/CSG-nPDS, have their respective gene expression profiles with different characteristics. Gene expression profile has certain referential significance in syndrome classification.</p>