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Polysaccharide of Balanophora involucrata Hook. f. (BPS), the major component of Balanophora involucrata Hook. f., was confirmed the protective effect on liver injury in our previous study. This research aimed to investigate the protective mechanism of BPS on experimental liver injury by attenuating cell ferroptosis through modulating solute carrier family 7 member 11/glutathione peroxidase 4 (SLC7A11/GPX4) pathway. The animal experiment was approved by the Experimental Animal Ethical Committee of Hubei Minzu University and all rats had received human care in compliance with the institutional animal care guidelines. Rats were given intraperitoneal injection of (D-galactosamine, D-GalN) solution (800 mg·kg-1) one time to establish the acute liver injury model. The results showed aspartate amino transferase (AST), alanine aminotransferase (ALT) and 4-hydroxynonenal (4-HNE) levels in serum were decreased, and the contents of reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA) and lipid peroxide (LPO) in liver tissues also decreased and glutathione (GSH) level increased after BPS administration with 200 mg·kg-1. Besides, BPS reduced iron deposition and increased the expression of SLC7A11 and GPX4 proteins in liver tissue. In conclusion, BPS ameliorated experimental liver injury by alleviating cell ferroptosis through SLC7A11/GPX4 pathway. The present study pointed to the possibility of utilizing BPS for protection against liver injury in clinic.
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OBJECTIVE@#To observe the effect of San-Ao Decoction (, SAD) on water metabolism of bronchial asthra model mice.@*METHODS@#Forty-five female BALB/c mice were randomly divided into control, model and SAD groups by a random number table, 15 mice in each group. A composite method with ovalbumin (OVA) sensitization and challenge was developed to establish bronchial asthma model. Mice in the control group were intraperitoneally injected with distilled water without aerosol inhalation challenge. On day 15-22, 0.3 mL SAD was administered via gastric route in SAD group, one time per day, while an equivalent volume of normal saline was used for gastric administration in the control and model groups. Changes in airway resistance in the inspiratory phase (RI-R-Area) were detected using an AniRes2005 system, and 5-h urine output was collected by metabolic cages. Histopathological changes in lung and kidney were observed by hematoxylin-eosin staining. mRNA expressions of aquaporin (AQP) 1 and AQP2 in kidney were detected by reverse transcription-polymerase chain reaction, and the protein expressions of AQP1 and AQP2 in kidney were detected by immunohistochemistry. Enzyme-linked immune sorbent assay was used to detect the OVA-specific endothelium-1 (ET-1), antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), prostaglandin E@*RESULTS@#Compared with the control group, the serum IgE level in model group increased (P<0.01). Following the pathologic changes in lung tissue, no significant change in kidney tissue was observed among 3 groups. Compared with the control group, the mice in the model group showed elevated airway resistance during inhalation phase, higher mRNA and protein expression levels on AQP1 and AQP2 in kidney tissue and higher ET-1 levels in serum, lung and kidney tissues, ADH and ANP in lung and serum, PGE@*CONCLUSION@#San-Ao Decoction can regulate the urine volume through regulating AQP1 and AQP2 expression, and the expression of these in the kidneys might be regulated by ET-1, NO and Ang II.
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Objective: The quality evaluation of herbal products remains a big challenge. Traceable markers are the core concept of the authentication of herbal products. However, the discovery of traceable markers is labor-intensive and time-consuming. The aim of this study is to develop a convenient approach to rapidly screen the traceable markers for herbal product authentication. Methods: Commercial Jing Liqueur and its 22 species of herbal ingredients were analyzed using HPLC-QTOF-MS and GC–MS to characterize nonvolatile and volatile chemicals. The acquired data were imported into MZmine 2 software for mass detection, chromatogram building, deconvolution and alignment. The aligned data were exported into a csv file and then traceable markers were selected using the built-in filter function in Excel. Finally, the traceable markers were identified by searching against online databases or publications, some of which were confirmed by reference standards. Results: A total of 288 chemical features transferred from herbal materials to Jing Liqueur product were rapidly screened out. Among them, 52 markers detected by HPLC-QTOF-MS were annotated, while nine volatile markers detected by GC–MS were annotated. Moreover, 30 of these markers were confirmed by comparing with reference standards. A chemical fingerprint consisting of traceable markers was finally generated to ensure the authentication and quality consistency of Jing Liqueur. Conclusion: A strategy for rapid discovery of traceable markers in herbal products using MZmine 2 software was developed.
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This study was designed to investigate the effect of dihydromyricetin (DHM) on inducing apoptosis of ovarian cancer cells A2780 through endoplasmic reticulum stress (ERS) pathway and the mechanisms involved in vitro and in vivo. A2780 cells were treated with different concentrations of DHM, and the protein expression levels of glucose-regulated protein 78 (GRP78) which is related to ERS increased, apoptotic proteins C/EBP-homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase-12) elevated. After pretreatment with ERS inhibitor, 4-phenyl butyric acid (4-PBA), following the intervention with DHM, the A2780 cell viability decreased and apoptotic rate increased. All animal welfare and experimental procedures were approved by the Animal Ethics Committee of Chongqing Medical University. Intraperitoneal injection of DHM suspension into nude mice with ovarian cancer could significantly inhibit the growth of transplanted tumor in vivo, increase the protein expression levels of GRP78, CHOP, and caspase-3. Moreover, swollen and broken endoplasmic reticulum could be observed in tumor tissues, suggesting that DHM intervention induces apoptosis mediated by ERS. The results indicated that DHM could induce apoptosis of ovarian cancer cells and inhibit the growth of transplanted tumors in nude mice, which might be related to the activation of ERS pathway.
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OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.
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Humans , Female , Middle Aged , Bone Density , Bile , Biomarkers , Absorptiometry, Photon , Osteoporosis, Postmenopausal , Cross-Sectional Studies , Bone Remodeling , Postmenopause , Collagen Type IABSTRACT
Objective:To explore the effect of trillin on oxidative stress response and nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in rats after spinal cord injury (SCI). Methods:A total of 108 male Sprague-Dawley rats were randomly divided into sham group (n = 36), model group (n = 36) and trillin group (n = 36), each group was divided into one day, three days and seven days subgroups, with twelve rats in each subgroup. The SCI model was established by modified Allen's heavy strike method in the model group and the trillin group, but no obvious injury in the sham group. The trillin group was given trillin 200 mg/kg every day, and the same amount of normal saline was given in the sham group and model group, twice a day. BBB score was performed one day, three days and seven days after modeling. Morphological changes were tested by Nissl's staining, and the changes of malonaldehyde (MDA) content and superoxide dismutase (SOD) activity were detected by ELISA seven days after modeling. The expression of Nrf2, Kelch like ECH associated protein 1 (Keap1), NAD(P)H quinone oxidoreductase (NQO1) and haemoxygenase 1 (HO-1) were detected by Western blotting one day, three days and seven days after modeling. Results:Compared with the model group, BBB scores increased (P < 0.05); the structure of spinal cord was more complete and the number of Nissl bodies increased; SOD activity increased (P < 0.05) and MDA content decreased (P < 0.05); the expression of Nrf2, Keap1, NQO1 and HO-1 increased (P < 0.05) in the trillin group. Conclusion:Trillin may play a protective role in spinal cord injury by inhibiting oxidative stress response and improving the motor function.
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Objective • To explore the value of the 2013 version of the ultrasound breast imaging reporting and data system (BI-RADS) classification diagnostic criteria combined with ultrasound shear wave elastography (SWE) to identify benign and malignant breast lesions. Methods • A total of 175 solid breast masses in 155 women were examined with ultrasound, and were judged to be benign or malignant by BI-RADS classification criteria. Then all the masses were examined with shear wave elastography (SWE), to obtain shear wave quantitative parameters of benign and malignant breast lesions, the pathological results were used as the gold standard to construct the receiver operating characteristic (ROC) curve of the subjects, which were used to compare the diagnostic value of the two methods alone and in combination. Results • The area under curve (AUC) of the BI-RADS classification diagnostic criteria, the Emax value, and the combination of the two methods to differential diagnosis of benign and malignant breast nodules were 0913, 0.884 and 0.957, respectively. Through pairwise comparison, there was significant difference in AUC between the two methods alone and their combination (BI-RADS classification vs. combination: Z=2.883, P=0.002; SWE vs. combination: Z=4.081, P=0.000). Conclusion • The combination of BI-RADS classification and SWE technology can improve the diagnostic accuracy of breast lesions.
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Objective · To explore the value of the 2013 version of the ultrasound breast imaging reporting and data system (BI-RADS) classification diagnostic criteria combined with ultrasound shear wave elastography (SWE) to identify benign and malignant breast lesions. Methods · A total of 175 solid breast masses in 155 women were examined with ultrasound, and were judged to be benign or malignant by BI-RADS classification criteria. Then all the masses were examined with shear wave elastography (SWE), to obtain shear wave quantitative parameters of benign and malignant breast lesions, the pathological results were used as the gold standard to construct the receiver operating characteristic (ROC) curve of the subjects, which were used to compare the diagnostic value of the two methods alone and in combination. Results · The area under curve (AUC) of the BI-RADS classification diagnostic criteria, the Emax value, and the combination of the two methods to differential diagnosis of benign and malignant breast nodules were 0913, 0.884 and 0.957, respectively. Through pairwise comparison, there was significant difference in AUC between the two methods alone and their combination (BI-RADS classification vs. combination: Z=2.883, P=0.002; SWE vs. combination: Z=4.081, P=0.000). Conclusion · The combination of BI-RADS classification and SWE technology can improve the diagnostic accuracy of breast lesions.
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Plant flowering regulation is an important mechanism to response to environmental stress. Heat shock protein 70 family is one of the main molecular chaperones to resist stress; miRNA can be used as a negative regulator to participate in post-transcriptional gene in flowering network. In this paper, we obtained an Hsp70 gene from Lonicera japonica transcriptome and combined with Lonicera japonica miRNA library to obtain a novel miRNA that may target Hsp70 gene through bioinformatics method. Bioinformatics and expression during different flowering stages of the obtained Hsp70 gene and miRNA were analyzed. Phylogenetic tree showed that the obtained Hsp70 gene was clustered with Hsp110 subfamily in Oryza sativa and Arabidopis thaliana. The prediction of miRNA secondary structure showed its stable structure and high reliability. The binding site map showed that there were two base mismatches between sequences of miRNA and Hsp70 gene. The expression analysis showed that the expression of Hsp70 and miRNA in different flowering stages had opposite trends, indicating that miRNA might regulate Hsp70 to participate in the flowering stages of Lonicera japonica. This study provided new ideas for Lonicera japonica flowering regulation and response to environmental stress mechanisms.
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Two cyclopeptides, celogentin L (1) and its epimer lyciumin A (2) were firstly isolated from Celosia argentea L.. The planar structures of the two compounds were fully determined by spectroscopic data, including 1D-, 2D-NMR, and HR-ESI/MS. The absolute configurations of amino acid components were assigned via chiral-phase HPLC analyses after acid hydrolysis. Furthermore, the configuration of C-N linkage at the glycine Cα was elucidated by extensive analyses of 2D-NMR and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cytotoxicity of the two compounds against human alveolar epithelial A549, hepatocellular carcinoma HepG2, and cervical cancer Hela cell lines was assayed. Although both of them were inactive in these cells, the present findings add new facets for the chemistry of Celosia argentea.
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Humans , A549 Cells , Cell Survival , Celosia , Chemistry , Chemistry Techniques, Analytical , HeLa Cells , Hep G2 Cells , Molecular Conformation , Molecular Structure , Peptides, Cyclic , Chemistry , Toxicity , Seeds , Chemistry , StereoisomerismABSTRACT
Two cyclopeptides, celogentin L (1) and its epimer lyciumin A (2) were firstly isolated from Celosia argentea L.. The planar structures of the two compounds were fully determined by spectroscopic data, including 1D-, 2D-NMR, and HR-ESI/MS. The absolute configurations of amino acid components were assigned via chiral-phase HPLC analyses after acid hydrolysis. Furthermore, the configuration of C-N linkage at the glycine Cα was elucidated by extensive analyses of 2D-NMR and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cytotoxicity of the two compounds against human alveolar epithelial A549, hepatocellular carcinoma HepG2, and cervical cancer Hela cell lines was assayed. Although both of them were inactive in these cells, the present findings add new facets for the chemistry of Celosia argentea.
Subject(s)
Humans , A549 Cells , Cell Survival , Celosia , Chemistry , Chemistry Techniques, Analytical , HeLa Cells , Hep G2 Cells , Molecular Conformation , Molecular Structure , Peptides, Cyclic , Chemistry , Toxicity , Seeds , Chemistry , StereoisomerismABSTRACT
A total of 58 varieties in Lonicera japonica from 20 producing areas were amplified by 22 pairs of SSR primers. Seven pairs of polymorphic primers were screened and their primers were used to establish DNA identity card and analyze genetic similarity.All the 58 varieties could be distinguished each other by the DNA identity card constituted by 7 pairs of core SSR primers.The genetic similarity coefficients of 58 varieties ranged from 0.366 7 to 0.916 7 by using PopGene32（vesion1.32）. Furthermore, all the varieties consistency were classified into 4 groups and constructed an evaluation table according to cluster analysis by an un-weighted pair-group average method with arithmetic mean. As expected, the results of cluster and evaluation table reflected 58 varieties relatives, which provide reference information for the selection of fine germplasm of L. japonica and the theoretical basis for the study of Dao-di herbs.
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LC-MS was used to detect 41 population of Lonicera japonica from different areas. LC-MS chemical chromatographic profile has been established. There were 23 common peaks, seventeen of which were identified according to reference standard and reference; SPSS software was applied to calculate the similarity of chemical fingerprints of 41 batches and the range was from 0.99 to 0.12. On this basis, the L. japonica's metabolites consistency was classified. Combined with comprehensive analysis of genetic identity, we can provide a theoretical basis for the authenticity research of Dao-di herbs and reference information for the breeding of excellent L. japonica.
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Aim To explore the effect of Shuanglong formula(SLF) on no-reflow in rats with myocardial is-chemia/reperfusion (I/R). Methods The rats were divided into five groups, namely, sham group, I/R group,SLF(5,2.5,1.25 g·kg-1)group. Treatment group received SLF decoction by gavage once a day for five days,while other groups were offered drinking wa-ter by gavage once a day for five days. The rats in I/R group and SLF-pretreated group were induced by iga-tion of left anterior descending coronary artery,and the rats were subjected to ischemia for 4h followed by reperfusion. Sham operation group did not undergo oc-clusion of the coronary artery. After 4 hours' reperfu-sion, real-time myocardial contrast echocardiography was used to monitor regional blood perfusion and cardi-ac functions. Blood was collected from the abdominal aorta and the serum was separated, and the levels of cTnT, CRP, CK and LDH were measured. The myo-cardial no-reflow area and infarction area were assessed by thioflavin S and nitrotetrazolium blue chloride, re-spectively. Results The SLF-pretreated group exhibi-ted significant reductions in the infarct area and no-re-flow area compared with I/R group(P <0.01 or P <0.05). In SLF-pretreated groups, β, A and A·β significantly increased as compared to those in I/R group. The LV anterior wall systolic and diastolic thicknesses (LVAW d/s) were significantly improved in SLF-pretreated group compared with those in I/R group. The LV internal diameter in systole (LVID s) and the LV volume in systole(LV s) were significantly reduced in SLF-pretreated group compared with those in I/R group. The EF, FS and SV were significantly improved in SLF-pretreated group compared with those in I/R group. The comparison between SLF-pretreated group and I/R group showed no significant difference in LDH, CK, cTnT, and CRP levels. Conclusion Shuanglong formula minimizes the sizes of myocardial infarct area and no-reflow area,improving regional my-ocardial blood flow and cardiac function.
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Objective:To delineate the distribution and abundance of interleukin 17 receptor mRNA in normal tissues of rhesus macaques.Methods:Tissue samples were collected from different systems including lymphoid system,digestive system and genital system and the mRNA levels of IL-17RA and IL-17RC were examined by real time RT-PCR.Meanwhile the levels of IL-17RA and IL-17RC mRNA in the PBMCs of rhesus macaques,African green monkeys and cynomolgus monkeys were examined.Results:IL-17RA mRNA was expressed in all the tested tissues and the levels were significantly different among these systems (P＜0.05).IL-17RC mRNA level in the large intestine was higher than that in the small intestine.IL-17RA mRNA level in rhesus macaque PBMCs was 3 and 5 times higher than that of cynomolgus monkeys and African green monkeys respectively,while IL-17RC mRNA in the PBMCs was below the limit of detection.Conclusion:IL-17RA is widely distributed in rhesus macaques;the expression level is different among different tissues and species.
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Objective To explore the effects of gravitational traction and target regulation of caspase3 on the degenerative intervertebral disc cells in rabbits.Methods Rabbits nucleus pulposus cells transfected with caspase3 siRNA or negative control siRNA were incubated in serum-starved medium for 6 hours and 48 hours.The expression of caspase3 siRNA and cell apoptosis were analyzed by RT-qPCR and Annexin V-fluorescein staining.In order to create intervertebral disc degeneration model,the right anterior side of the annulus fibrosus of lumbar vertebrae of 35 rabbits were damaged by 16-gauge needle.After confirming the success of modeling,35 animal models were randomized into 3 groups:model group (n=10),negative siRNA group (n=10) and caspase3 siRNA group (n=5).Either negative control siRNA or caspase3 siRNA was injected into the center of nucleus pulposus using a 26-gauge needle from the left anterior side,while the model group received no injection.Nucleus pulposus tissue of 5 rabbits selected randomly from every group after 48 hours were analyzed by PCR and Western blotting for caspase3 mRNA and protein expressions.Half of the casepase3 siRNA group were selected randomly and received a routine gravitational traction using a model of our own design,30min per day for 2 weeks,while other groups received no treatment.TNF-o and IL-1β expression levels and histopathological observations were performed after intervention.Results Expression of caspase3 mRNA in rabbit nucleus pulposus cells transfected with caspase3 siRNA decreased obviously in serum-starved medium,and the apoptosis rate of cells cultured in serum-starved medium decreased significantly (P＜0.05).Caspase3 mRNA and caspase3 protein expression of nucleus pulposus injected by caspase3 siRNA down-regulated in the caspase3 siRNA group.Compared with model group and negative control siRNA group,TNF-α and IL-1β expression levels of caspase3 siRNA traction group decreased significantly (P＜0.05),but there was no statistical significance compared with caspase3 siRNA group (P＞0.05).Pathological observation revealed that viable cell number and extracellular matrix contents increased and collagenous fibers arranged regularly in caspase3 siRNA traction group.Conclusion Gravitational traction and target regulation of caspase3 can prevent apoptotic cell death and delay early intervertebral disc degeneration.
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Purpose To investigate the clinicopathological features and differential diagnosis of congenital nonprogressive hemangiomas in children.Methods The clinic pathologic data and follow-up results of 19 cases of congenital nonprogressive hemangiomas were collected.The histopathologic features of congenital nonprogressive hamangiomas were observed with HE staining and immunohistochemistry of EnVision two-step.Results Of the 19 patients,13 were males and 6 were females,with an average age of 52.4 months and medium age of 48 months.9 cases occurred in the limbs and trunk,10 lesions were located in head and face included 1 case with multifocal lesions.Grossly,the specimens were irregular solid mass with range from 0.4 cm to 7 cm in maximum diameter.Microscopically,the lesions were composed of capillary lobules that separated by abnormal dense fibrotic dermal stroma typically containing a prominent component of large vessels.Immunohistochemically,the tumor cells were positive for CD31,CD34,and WT1,but negative for D2-40 and GLUT1.All eases underwent surgical resection,and the follow-up period was 1-24 months.There was no recurrence or metastasis.Conclusion Congenital nonprogressive hemangioma is a rare benign vascular tumor in children,with characteristic clinical and pathologic features.So the exact diagnosis is very important for both pathologists and clinicians.
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Ginsenosides are the main active ingredient and allelochemicals of Panax ginseng, and they play an important role in ginseng growth and in ecological adaptation. To study the influence of ginsenosides on soil microbial communities, the method of given exogenous total ginsenosides of different concentrations were used to study the influence of ginsenosides on new forest soil microbial community, evaluate the change of metabolic activity of microbial community and investigate the ecological effect of ginsenosides on soil microbial community. Results showed that, exogenous total ginsenosides promoted metabolic activity of microbial community in new forest soil at different concentrations compared with the control after 10 d and 40 d treatment. After 10 d,except for the Evenness index, all of the other indices indicated that the functional diversity of the soil microbial community in the new forest firstly increased then decreased with increase of the total ginsenosides concentration. The Substrate richness for 0.01 g•L⁻¹ soil treatment was significantly different from that of the control. After 20 d, 30 d and 40 d, except for the Evenness index, all of the other indices indicated that the functional diversity of the soil microbial community in the new forest increased with total ginsenosides. These results suggested that ginsenosids can change soil microbial community and microbial metabolic activity, which alter soil microbial ecology and accordingly affect the growth of ginseng with accumulation of ginsenosides in the soil.
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Plate assay and spore germination method were used to study the chemotaxis response of Alternaria panax to arginine, glutamic acid, aspartic acid and threonine. The result showed that the optimum temperature of A. panax chemotaxis response to four amino acids were all 25 ℃. And chemotaxis responses of A. panax were different under conditions of different concentration and pH value. The chemotaxin reached to the highest under the condition of 2 mg•L⁻¹ and pH value was 7 for arginine, glutamic acid and threonine while 20 mg•L⁻¹ and pH value was 6 for aspartic acid . The data of chemotactic migration index (CMI) were 1.24, 1.38, 1.27, 1.31 and chemotactic growth rates(CGR) were 0.451 0, 0.353 0, 0.381 3, 0.228 8 and spores germination rates(SGR) were 57.33%，63%，56.67%，58% and the dry weight of mycelial (DWM) were 372.9, 348.5, 314.4, 390.2 mg•L⁻¹ respectively. It indicated that the low and middle concentration of amino acid had significant promoting effect on chemotaxis response of A. panax. As important substances generated in ginseng root, amino acids exhibited an efficient chemotactic effect on A. panax, and some even show inhibition effect under high concentration.
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Safety issues of traditional Chinese medicine injections has been heated debate. There are two diametrically opposed views: it should be used reasonable and developed healthily or be forbidden to use. Some people have many misunderstandings and prejudices about the safety of traditional Chinese medicine injections. Compared with western medicine,traditional Chinese medicine has its own particularity. Traditional Chinese medicine has complex components. Its research and clinical application is different from western medicine. Adverse reactions of traditional Chinese medicine injections are related to many factors,such as a large number of irrational use,blind use of traditional Chinese medicine injections and western medicine injections,counterfeit and substandard drugs,incorrect methods of intravenous infusion,toxicity of supplementary materials,drug ingredients. Developing traditional Chinese medicine injection is the need for curing sickness to save patients. The purposeful, targeted, organized and planned systematic research of traditional Chinese medicine injections should be strengthened,especially the safety of traditional Chinese medicine. Strengthen supervision and control of rational drug use.Strengthen the examination and approval,supervision and management of all aspects to ensure the safety of patients.