Effect of guarana on lipid metabolism in obese rats: a study based on lipidomics / 中国中药杂志

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid β-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid β-oxidation, thereby improving rat obesity and dyslipidemia.

Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism / 中国中药杂志

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Effectiveness of FibroTouch combined with four hepatic fibrosis biomarkers for evaluation of the liver fibrosis degree among patients with chronic schistosomiasis-induced liver disorders / 中国血吸虫病防治杂志

Objective To evaluate the performance of FibroTouch in combination with four hepatic fibrosis biomarkers for assessment of the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver disorders. Methods A total of 63 patients with chronic schistosomiasis-induced liver diseases admitted to The Third People’s Hospital of Kunshan City from January to March 2021 were enrolled as the observation group, while 50 healthy volunteers receiving health examinations in the hospital during the study period were randomly selected as the control group. The liver stiffness measurement (LSM) was determined using the FibroTouch technique, and the serum levels of four hepatic fibrosis biomarkers were detected using chemilumi-nescence immunoassay, including type IV collagen (IV-C), type III procollagen (PC-III), hyaluronidase (HA) and laminin (LN). The receiver operating characteristic (ROC) curves of LSM and four hepatic fibrosis biomarkers alone and in combination for assessing the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver disorders were plotted and the area under the ROC curve (AUC) was estimated to examine the value of LSM and four hepatic fibrosis biomarkers alone and in combination for assessing the degree of hepatic fibrosis. Results There were 63 subjects in the observation group, including 28 men and 35 women, and the participants had a mean age of (65.34 ± 12.56) years and a mean body mass index (BMI) of (24.47 ± 11.05) kg/m2. There were 50 subjects in the control group, including 22 men and 28 women, and the participants had a mean age of (64.28 ± 13.10) years and a mean BMI of (25.12 ± 11.64) kg/m2. There were no significant differences between the observation and control groups in terms of gender ratio (χ2 = 0.002, P > 0.05), age (t = 0.437, P > 0.05) or BMI (t = 0.303, P > 0.05). The LSM [(8.65 ± 5.22) vs. (3.24 ± 1.10) kPa; t = 8.013, P < 0.05], IV-C [(51.80 ± 9.45) vs. (30.10 ± 10.34) ng/L; t = 11.506, P < 0.05], PC-III [(77.28 ± 17.22) vs. (48.62 ± 9.54) ng/L; t = 11.224, P < 0.05], HA [(39.55 ± 5.32) vs. (84.89 ± 10.34) ng/L; t = 30.158, P < 0.05] and LN [(99.47 ± 7.37) vs. (61.93 ± 9.80) ng/L; t = 22.496, P < 0.05] were significantly greater in the observation group than in the control group, and Spearman correlation analysis showed that the degree of liver fibrosis positively correlated with LSM (rs = 0.675, P < 0.01), IV-C (rs = 0.421, P < 0.01), PC-III (rs = 0.517, P < 0.01), HA (rs = 0.550, P < 0.01) and LN (rs = 0.539, P < 0.01) among patients with chronic schistosomiasis-induced liver diseases. ROC curve analysis revealed that the AUC of LSM for assessment of the hepatic fibrosis degree was 0.884 (P < 0.001), and the LSM cutoff, sensitivity and specificity were 11.75 kPa, 71.43% and 84.00% at the highest Youden index, respectively. In addition, the AUC of four hepatic fibrosis biomarkers for assessment of the hepatic fibrosis degree was 0.577 to 0.670, with 70.174 to 115.237 ng/L cutoff values, 17.46% to 68.25% sensitivity and 71.01% to 96.00% specificity. In addition, the sensitivity and specificity of LSM combined with four hepatic fibrosis biomarkers were 92.06% and 95.07% for assessment of the hepatic fibrosis degree among patients with chronic schistosomiasis-induced liver diseases. Conclusion FibroTouch in combination with detection of four hepatic fibrosis biomarkers has a high sensitivity and specificity for assessing the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver diseases, which deserves widespread clinical uses.

Mechanism analysis of repeatedly steamed and sundried Rehmanniae Radix Praeparata in delaying brain aging in ovariectomized mice based on proteomics / 中国中药杂志

The present study explored the effect and mechanism of repeatedly steamed and sundried Rehmanniae Radix Praeparata(RRP) in delaying brain aging in ovariectomized mice. After ovariectomy, the mice were randomly divided into a model group, an estradiol valerate group(0.3 mg·kg~(-1)), and low-(1.0 g·kg~(-1)), medium-(2.0 g·kg~(-1)), and high-dose(4.0 g·kg~(-1)) RRP groups, and a sham operation group was also set up, with 15 mice in each group. One week after the operation, intragastric administration was carried out for 15 consecutive weeks. The step-down test and Morris water maze test were used to detect the behavioral changes of mice. HE staining and Nissl staining were used to observe the morphological changes of mouse brain tissues. Immunohistochemistry was used to detect the expression of Aβ and ER_β in mouse brain tissues. The serum estrogen levels and cholinesterase and cholinesterase transferase levels in brain tissues of mice were detected by assay kits. The extracted hippocampal protein was detected by the Nano-ESI-LC-MS system, identified by the Protein Discovery, and analyzed quantitatively and qualitatively by the SIEVE. The PANTHER Classification System was used for GO analysis and KEGG pathway enrichment analysis of the differential proteins. Compared with the sham operation group, the model group showed decreased learning and memory ability, shortened step-down latency(P<0.05), prolonged escape latency(P<0.05), reduced platform crossings and residence time in the target quadrant, scattered nerve cells in the hippocampus with enlarged intercellular space, increased expression of Aβ-positive cells(P<0.05), declining expression of ER_β-positive cells and estrogen level(P<0.05), and weakened cholinergic function(P<0.05). Compared with the model group, the RRP groups showed improved learning and memory ability, prolonged step-down latency(P<0.05), increased estrogen level(P<0.05), neatly arranged nerve cells in the hippocampus with complete morphology, declining Aβ-positive cells, and elevated expression of ER_β-positive cells. A total of 146 differential proteins were screened out by proteomics, and KEGG pathway enrichment yielded 75 signaling pathways. The number of proteins involved in the dopaminergic synapse signaling pathway was the largest, with 13 proteins involved. In summary, RRP can delay brain aging presumedly by increasing the level of estrogen, mediating the dopaminergic synapse signaling pathway, and improving cholinergic function.

Study on time-toxicity relationship and mechanism of Gardeniae Fructus extract on hepatoxicity in rats based on proteomics / 中国中药杂志

To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.

Effect of Erjingwan on Hippocampal Proteomics in AD Rats with Kidney Yin Deficiency Induced by Ovariectomy+ D-Galactose Combined with Aβ1-40 / 中国实验方剂学杂志

Objective::To explore the effect of Erjingwan on the biological basis of kidney yin deficiency Alzheimer' s disease(AD)rats induced by ovariectomy+ D-galactose combined with amyloid beta1-40 (Aβ1-40). Method::After ovariectomy, rats were randomly divided into five groups: model group, positive group, Erjingwan high, medium and low dose group, 11 rats in each group, and 11 rats in sham operation group. One week after operation, D-galactose was injected intraperitoneally for 7 weeks, and four weeks after operation, Aβ1-40 was injected unilaterally into hippocampus. The rats in model group and sham-operation group were given saline by intragastric administration 3 weeks after operation. The rats in high, middle and low dose groups of Erjingwan were given corresponding concentration (9.0, 4.5, 2.25 g·kg-1). The rats in positive control group were given Donepezil 1.0 mg·kg-1 with dosage of 10 mL·kg-1 once a day for 35 consecutive days. After 30 days of administration, the learning ability of the rats were examined using a Y-maze. The hippocampus tissues of rats were isolated. The morphology of hippocampus was observed by Nissl staining.The proteins were detected by Nanol-ESI liquid-mass spectrometry system and identified by protein Discovery software. Relative quantitative and qualitative analysis of differential proteins in hippocampus was performed by SIEVE software, and Gene Ontology of differential protein was performed by PANTHER Classification System database. String analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were performed on the differential proteins. Result::Compared with model group, the correct rate of Y maze in the high and middle dose groups of Erjingwan was significantly raised(P<0.05), and the number of neurons in the hippocampal CA1 area was significantly increased(P<0.01).115 differential proteins (Ratio>1.5 or Ratio<0.5) such as Insulin-like growth factor 1 receptors(IGF-1R) were found in the high-dose group of the Erjingwan group as well as 94 differential proteins such as Synaptophysin expressed in the middle-dose group of the Erjingwan. And there are 87 differential proteins such as Acetyl-CoA acetyltransferase-cytosolic in the positive drug group. It showed that these proteins were mainly divided into tubule-related proteins, heat shock proteins, energy metabolism-related proteins and AD-related proteins with GO analysis. It was found that the above differential proteins involved 93 signaling pathways such as Dopaminergic synaps by KEGG analysis. Conclusion::Erjingwan can improve cognitive impairment and neuronal damage in rats with kidney yin deficiency, possibly by altering the expression of multiple pathway-associated proteins such as phosphatidylinositol 3-kinase/protein kinase B signaling pathway(PI3K/Akt), insulin signaling pathway, and adenylate-activated protein kinase (AMPK)signaling pathway, estrogen signaling pathway, and Dopaminergic synapse.

Exploration of Active Ingredients and Anti-breast Cancer Mechanism of Glycyrrhizae Radix Et Rhizome and Aurantii Fructus Based on Network Pharmacology / 中国实验方剂学杂志

Objective::To explore the potential active ingredients and possible anti-breast cancer mechanism of Glycyrrhizae Radix et Rhizome and Aurantii Fructus based on the method of network pharmacology. Method::The main potential targets of Glycyrrhizae Radix et Rhizome and Aurantii Fructus on breast cancer were summarized by comparing the Glycyrrhizae Radix et Rhizome-Aurantii Fructus active ingredients screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and breast cancer targets searched in Therapeutic Target Database (TTD). Cytoscape 3.7.1 software was used to establish a Glycyrrhizae Radix et Rhizome-Aurantii Fructus active ingredients-target-disease network and perform topology analysis based on the network. Result::According to related conditions of drug-like (DL) and oral bioavailability (OB), the network of Glycyrrhizae Radix et Rhizome-Aurantii Fructus active ingredients-breast cancer target was obtained, covering a total of 133 nodes, 116 chemical components and 17 breast cancer drug targets, 109 active components of Glycyrrhizae Radix et Rhizome interacting with breast cancer drug target, 6 active ingredients of Aurantii Fructus interacting with breast cancer drug targets, and 1 common active ingredient of Aurantii Fructus and Glycyrrhizae Radix et Rhizome interacting with breast cancer targets. There were 400 breast cancer target-interaction target pairs in the network diagram. Conclusion::The anti-breast cancer effect of Glycyrrhizae Radix et Rhizome and Aurantii Fructus is based on the overall pharmacodynamic effect of multi-component, multi-pathway and multi-target, the investigation of its potential anti-breast cancer mechanism provides theoretical basis for further experimental research.

Investigation on Rehabilitation Therapists Practitioners under Medical-Exercise Integration in China / 中国康复理论与实践

Objective:To investigate the integration of medicine and exercise in China in rehabilitation therapists practitioners. Methods:From May to June, 2019, rehabilitation therapists in provincial and municipal medical institutions, health management centers and rehabilitation institutions nationwide were surveyed with Wenjuanxing online questionnaires, which included basic information, geographical distribution, nature of work units, occupational characteristics, educational background, years of working and awareness of exercise prescriptions. Results:A total of 2935 rehabilitation-related employees were involved, which included 1387 male and 1548 female in 31 provinces. In all the respondents, 1505 of them (51.28%) worked in tertiary hospitals and 1015 (34.58%) in secondary hospitals; 2182 (74.34%) worked on physical therapy, 947 (32.27%) on occupational therapy, 553 (18.84%) on speech therapy, 141 (4.80%) on rehabilitation engineering, and 846 (28.82%) on exercise rehabilitation; 2218 (75.57%) were with junior title and 592 (20.17%) with intermediate title; 24 (0.82%) were with secondary school education, 724 (24.67%) with junior college degree, 2011 (68.52%) with bachelor's degree, and 160 (5.99%) with master's degree or above; 785 (26.75%) fully understood, 1025 (34.92%) understood and 1009 (34.38%) basically understood the concept of exercise prescription. Conclusion:Rehabilitation therapy is widely spread in China, however, the geographical distribution is uneven. Rehabilitation related practitioners are diversified in professional direction, and full-time job is not top-notch. The level of education is generally low, and talent cultivation needs to be strengthened. The integration of medicine and exercise is developing, and exercise prescriptions are widely available. It is necessary to cultivate a considerable number of high-quality professionals to coordinate the integrated development of medicine and exercise, to improve the quality of rehabilitation services and promote the development of medicine and exercise integration.

Autophagic activity of piperine on small intestine in dementia model mice with Parkinson's disease / 中国中药杂志

This article is to investigate the effect of piperine on the small intestine of mice with Parkinson's disease with dementia(PDD). Ninety-six C57 BL/6 mice of SPF grade were randomly divided into 8 groups(male, 12 in each group): normal group, model group, autophagy inhibitor group(6-amino-3-methylpurine, 3 MA, 30 mg·kg~(-1)), autophagy activator group(rapamycin, 1 mg·kg~(-1)), low, medium, and high dose piperine groups(10, 20, 40 mg·kg~(-1)), and medopar group(112.5 mg·kg~(-1)). Except for the normal group, mice in each group were injected subcutaneously with reserpine(0.1 mg·kg~(-1)) once every 48 hours for 40 days. In addition, on the 20 th day of administration, except for the normal group, the mice in the other groups were subjected to bilateral common carotid artery occlusion to finally prepare PDD models. At the same time, each group was given the corresponding drug treatment once a day for 40 days. After the last administration, the behavioral changes of mice were observed by autonomic activity experiment and hot plate experiment. The expression levels of α-synuclein(α-syn) and tyrosine hydroxylase(TH) in the small intestine were detected by immunohistochemistry. The expression levels of beclin-1, microtubule-associated protein 1 light chain 3 B(LC3 B) and p62 in the small intestine were detected by immunofluorescence assay. Hematoxylin-eosin staining was used to observe the pathological morphology of small intestine tissues in each group. Enzyme-linked immunosorbent assay was adopted for detection of β-amyloid precursor protein(APP), p-tau, acetylcholine transferase(ChAT), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in small intestine. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of α-syn, TH, beclin-1, microtubule-associated protein 1 light chain 3(LC3), and p62 mRNA and mmu-miR-99 a-5 p in the small intestine. The results of this study showed that, as compared with the model group, the number of activities, the expression levels of ChAT, TH, and p62 were significantly increased in the 3 MA group, the various piperine dose groups, and the medopar group(P<0.05), and their first foot licking time was shortened; APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly reduced(P<0.05). However, as compared with the model group, the number of activities, ChAT, TH, and p62 expression levels in the rapamycin group were significantly reduced(P<0.05), and the APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). As compared with the 3 MA group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in the low and medium dose piperine groups and rapamycin group(P<0.05); howe-ver, their first foot licking time was significantly prolonged, APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were increased significantly(P<0.05). As compared with the medopar group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in low dose piperine group and rapamycin group(P<0.05), but their first foot licking time was significantly extended, and APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). In addition, as compared with the normal group, the small intestinal epithelial cells of the model group and the rapamycin group were shed off a lot, with severe damages of intestinal mucosa as well as edema and shedding of the small intestine villi. After administration of the therapeutic interventions, the small intestinal epithelial cells of the 3 MA group, each dose group of piperine, and the medopa group were slightly damaged and the villi were slightly shed off. In summary, piperine has a protective effect on the small intestine of PDD model mice, showing reduced expression of mmu-miR-99 a-5 p, pro-inflammatory factors and autophagy factors, and the mechanism of slowing PDD pathological symptoms may be related to the inhibition of autophagy.

Chemical Constituents of Lipid-soluble Parts of Tinospora sinensis / 中国实验方剂学杂志

Objective:To isolate the chemical constituents from lipid-soluble parts of Tibetan Tinospora sinensis and identify the structure of the monomer compounds. Method:Eighty kg of dried rhizomes of T. sinensis were soaked by 80% ethanol (5 times of the dose of crude drug) for 1 hour, boiled under reflux for 1 hour,then and filtered. The above steps were repeated. The two extracts were combined,and the solvent was recovered to obtain a total extract. The obtained extract was extracted with a conventional solvent,and the solution was recovered to obtain petroleum ether extract,methylene chloride extract,ethyl acetate extract,n-butanol extract and water extract. Methylene chloride extract was isolated and purified by silicagel column chromatography,semi-preparative liquid chromatography and SephadexLH-20 chromatography; the chemical structure was identified on the basis of ESI-MS,nuclear magnetic resonance (1H-NMR and 13 C-NMR) spectroscopy data and literatures. Result:Fifteen compounds were isolated and identified respectively as n-dodecanol (1),n-hexacosanol (2),palmitic acid (3),dibutyl phthalate (4),vanillic acid (5),vanillin (6),apocynin (7),tinocordifolioside (8),medioresinol (9),isolariciresinol (10),aurantiamide (11),aurantiamide acetate (12),berberine (13),daucosterol (14),β-sitosterol (15). Conclusion:Except for 3,4,6,14,15,the other 10 compounds were isolated from the plant for the first time.

Network pharmacology-based study on mechanisms of antipyretic action of Pueraria radix / 药学学报

This study was designed to explore the antipyretic mechanism of Pueraria radix. The method of network pharmacology was used to determine the known ingredients corresponding to Pueraria radix, predict the drug-related gene /protein targets, and analyze the interplay between key ingredients and targets. Biological Information Annotation Databases (DAVID) was used to enrich the biological processes and pathways. The result of network analysis was validated by molecular docking. It was found that 49 active ingredients of Pueraria radix not only regulate 21 targets (e.g. PTGS2, EGFR), but also affect 11 biological processes (e.g. oxidation-reduction process, prostaglandin synthesis, positive regulation of fever generation and inflammatory response) and 7 metabolic pathways (arachidonic acid metabolism, serotonergic synapse and HIF-1, et al). Molecular docking results showed that more than 65% of the active ingredients could be well docked with key targets, and the relevant literatures indicated that the active components could inhibit the expression of PTGS2, which means the result has a high reliability. These results indicated that Pueraria radix may carry its pyretic action via a "multi-ingredients-multi-targets-multi-pathways" mode, which provides a scientific basis for further research and drug development.

Prognostic values of preoperative serum CA199 and NSE on esophageal squamous cell carcinoma patients / 中华疾病控制杂志

Objective To explore the effects of preoperative serum cancer antigen 19-9 (CA19-9) and neuron-specific enolase (NSE) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods This prospective study enrolled 176 patients with ESCC. 2 test was used to analyze the relationship between CA19-9, NSE and general clinical features. Survival curves were estimated using Kaplan-Meier method and comparisons were performed using the log-rank test. The Cox proportional hazards model was performed for multivariate analyses of overall survival (OS) and disease free survival (DFS). Results The patients with both high CA19-9 and NSE had the poor prognosis compared with those had both low CA19-9 and NSE (OS: HR=2.310, 95% CI: 1.208-4.418; DFS:HR=2.354, 95% CI：1.265-4.381). Compared to the separate detection of the two markers, the combined detection of CA19-9 and NSE was more accurate in the prognosis prediction of patients with ESCC (OS:C-index=0.686; DFS:C-index=0.684). Conclusions Preoperative serum CA19-9 and NSE were risk factors for the prognosis of patients with ESCC. Combined detection had higher accuracy of prediction of prognosis in patients with ESCC.

Cordycepin protects against β-amyloid and ibotenic acid-induced hippocampal CA1 pyramidal neuronal hyperactivity

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A₁ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A₁R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

Advantage of cold snare resection for anticoagulant therapy in patients with small colonic polyps / 中国内镜杂志

Objective To study the safety of cold snare in colon polyps of anticoagulant patients. Finding a safe and convenient way to remove small polyps in the colon in patients receiving anticoagulant therapy. Methods In our hospital outpatient and inpatient colonoscopy findings of colonic polyps (3 ～ 8 mm diameter) of the 60 patients received anticongulation treatment as the research object, randomly divided into cold trap group and high frequency electrocoagulation group, 30 cases in each, using cold trap technology, high frequency electrocoagulation technology excision of polyps respectively. Comparison of the two groups of patients with polyp location, size, quantity, resection time, intraoperative and postoperative bleeding rate, the rate of complete resection of colonic polyps, sample recovery rate, pathological examination results and pathological specimens in submucosal arteriole injury. Results The average age of the two groups was (46.76 ± 8.52) years, gender, colonoscopy indication, bowel preparation score and ileal intubation success rate differences has no significant difference (P > 0.05), comparable; cold trap group polyps operation time (3.26 ± 0.84) min, the high frequency electrocoagulation group (5.17 ± 1.25) min, the difference between the two groups was significant (P < 0.05); cold trap group polyp complete resection rate was 100.00％ (57/57), high frequency electrocoagulation group was 88.68％ (47/53), the two groups had significant difference (P < 0.05); the average number of the two groups of patients with polyps, polyp diameter, the location, intraoperative bleeding, postoperative bleeding and polyps from two weeks of recovery rate showed no significant difference (P > 0.05); the two groups of patients with pathological type and specific differences had no statistically significance (P > 0.05); cold trap group specimens of stick : there was no damage in the arteriole of the submucosa, and 7 cases in the high-frequency electrocoagulation group were impaired, and the difference between the two groups was significant (P < 0.05). Conclusion For the resection of anticoagulation for patients with high frequency, electric coagulation and cold trap compared to traditional small polyps excised colon has more secure, convenient and accurate pathological and other advantages, but limited to the single center, low sample size conditions, cold trap technology by therapeutic effect and advantages of anticoagulant therapy in patients still need to be further studied.

Study on Material Basis and Mechanism of Erzhi Wan prevent Alzheimer's disease by network pharmacology / 中国中药杂志

The present study is to explore the material basis and mechanism of Erzhi Wan the prevented Alzheimer's disease by using network pharmacology. The key target of Alzheimer's disease was docked with the Erzhi Wan compounds, and the drugs-target combined with target-signal pathway network model was established by Cytoscape 3.2.1 software. Thirty compounds have a strong interaction with key target of Alzheimer's disease and three key pathways related with Wnt, MAPK and PI3K-Akt-mTOR. There are 5 ingredients such as quercetin,geraniol,beta-sitosterol,nerol,eriodictyol that could be verified from literature.This result initially revealed the material basis for Erzhi Wan for Alzheimer's disease and the mechanism in terms of three signaling pathways. The network pharmacology method found that the active ingredients of Erzhi Wan for Alzheimer's disease may be quercetin,geraniol,beta-sitosterol,nerol,and eriodictyol, and the mechanism may be related to three signal pathways including Wnt, MAPK, and PI3K-Akt-mTOR.

Effects of tetramethylpyrazine on trigeminal neuralgia induced by chronic constriction injury of infraorbital nerve in rats / 生理学报

Trigeminal neuralgia (TN) is a kind of recurrent transient and severe pain that is limited to the trigeminal nerve in one or more branches. The clinical incidence of TN is high, which seriously affects the quality of life of the patients and is difficult to cure. The present study investigated the effects of tetramethylpyrazine (TMP) on TN induced by chronic constriction injury of the infraorbital nerve (ION-CCI) in rats. Adult male Sprague-Dawley rats were randomly assigned to four groups: sham, sham treated with TMP (Sham+TMP), TN model (TN), and TN treated with TMP (TN+TMP). The rat TN model was established by ION-CCI and TMP (50 mg/kg) was injected intraperitoneally once a day for 2 weeks after operation. The mechanical response threshold was tested by the electronic von Frey filaments. The expression of CGRP in the trigeminal ganglia (TGs) of rats on the operative side was detected by RT-PCR, immunohistochemical staining and Western blot. In 15 days after operation, TN group showed a robust decrease in mechanical response threshold as compared with sham group. From day 9 to day 15 after operation, TMP treatment significantly suppressed the TN-induced mechanical hyperalgesia (P < 0.05). On day 15 after operation, RT-PCR, immunohistochemical staining and Western blot analysis showed an obvious increase in expression level of CGRP in TGs of TN group compared with sham group, which was downregulated by TMP treatment (P < 0.05). These results suggested that TMP might have a therapeutic potential for the treatment of TN through regulating CGRP expression in the TGs.

Proteomics research of intervention effect of "Qi enriching" herbs on "Qi deficiency" rats based on technology of NanoLC-LTQ-Orbitrap / 中国中药杂志

Proteomics method, based on NanoLC-LTQ-Orbitrap technology, was applied to explore the biological basis of intervention effect of "Qi enriching" herbs on "Qi deficiency" rats. The "Qi deficiency" rat model was established with caloric restriction combined with excessive swimming. Muscle proteins of vastus lateralis from the blank group, the model group and the ginseng group were detected by NanoLC-LTQ-Orbitrap system. The data were imported into Protein Discovery software to identify the proteins and all the raw datum were analyzed by SIEVE software. Compared with model group, 26 significant difference proteins were found in ginseng group, which the variation trend was consistent with the blank group. Through the biological function analysis, the found proteins could be classified into proteins involved in energy metabolism, proteins involved in glucose metabolism, electrolyte balance and material transfer related proteins, inflammation related protein and cytoskeleton protein. The above target proteins and their regulation pathways may be the biological basis which ginseng played a role of tonifying "Qi" of "Qi deficiency" symptom.

Effects of extractionfrom raspberry on hippocampus proteomics of mice suffered from ovariectomized-induced AD / 中国中药杂志

This paper was aimed to investigate the impact of the extraction from raspberry on the Alzheimer disease model protein expression. According to weight, the ovariectomized mice were randomly divided into shame operation group, model group, estrogen positive control group(0.1 g•L⁻¹) and ethyl acetate extraction part control group(in dose of 18 g•kg⁻¹). Each mouse in positive control group was subcutaneous injected of estradiol with 0.2 mL every two days. Raspberry effective parts group were given 0.01 mL•g⁻¹ raspberry ethylacetate extracts, model group and control group were given 0.01 mL•g⁻¹ saline once a day. The drug administration lasted for 32 days. Proteins from mice's hippocampus were extracted, then Nanol-ESI liquid-mass spectrometry system was used for detection and ProteinDiscovery software was used for identification to qualitative analysis different groups of hippocampal proteins by using the software of SIEVE. The results showed that model group compared with the mice of ethyl acetate extraction part control group have 66 differentially expressed proteins including heat shock protein, microtubule protein, protein involved in energy metabolism and protein of brain protection related proteins associated with AD. Those differences protein may be the target that Raspberry prevention and treatment of AD.

Simvastatin inhibits apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax / 世界急诊医学杂志（英文）

@#BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The present study aimed to investigate the role of simvastatin in apoptosis of endothelial cells induced by sepsis and its mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into three groups: control group, sepsis serum intervention group (sepsis group) and simvastatin+sepsis serum intervention group (simvastatin group). After 24-hour incubation with corresponding culture medium, the relative growth rate of HUVECS in different groups was detected by MTT assay; the apoptosis of HUVECs was detected by Hoechst33258 assay and flow cytometry; and the expression of the Bcl-2 and Bax genes of HUVECs was detected by PCR. RESULTS: Compared with the sepsis group, HUVECs in the simvastatin group had a higher relative growth rate. Apoptotic HUVECs decreased significantly in the simvastatin group in comparison with the sepsis group. Expression of the Bcl-2 gene in HUVECs decreased obviously, but the expression of the Bax gene increased obviously after 24-hour incubation with sepsis serum;however, the expression of the Bcl-2 and Bax genes was just the opposite in the simvastatin group. CONCLUSIONS: Our study suggests that simvastatin can inhibit apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. It may be one of the mechanisms for simvastatin to treat sepsis.

Study on discrimination mode of cold and hot properties of traditional Chinese medicines based on biological effects / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of cold or hot properties of traditional Chinese medicines (TCM) on biological effect indexes, and analyze the contribution of variables on cold or hot properties, in order to preliminarily establish the discrimination mode for the biological effects of cold or hot properties.</p><p><b>METHOD</b>Rats were randomly divided into the blank control group, cold TCM groups (Coptidis Rhizoma, Scutellariae Radix, Phellodendri Cortex, Gardeniae Fructus, Sophorae Flavescentis Radix and Gentianae Radix) and hot TCM groups (Aconiti Lateralis Preparata Radix, Zingiberis Rhizoma, Alpiniae Officinarum Rhizoma, Zanthoxyli Pericarpium, Cinnamomi Cortex and Evodiae Fructus), and orally administered with 10 mL x kg(-1) of corresponding TCM water decoctions for 30 d, twice a day. Altogether 53 biological effect indexes correlated to cold or hot properties of traditional Chinese medicines were founded by searching literatures. The data warehouse were established by using data-mining software Clementine12.0. Data of the blank control group, cold TCM groups (Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, Sophorae Flavescentis Radix, Gentianae Radix) and hot TCM groups (Aconiti Lateralis Preparata Radix, Zingiberis Rhizoma, Alpiniae Officinarum Rhizoma, Zanthoxyli Pericarpium, Cinnamomi Cortex) were selected into a training set. C5.0 algorithm and C&R classification and regression algorithm were adopted to define the importance of variable, create the decision trees, and test hot or cold properties of Evodiae Fructus and Scutellariae Radix.</p><p><b>RESULT</b>According to C&R classification and regression algorithm, SDH activity of livers was the most important hot or cold property, with the significance closed to 30%. It was followed by triglyceride, liver Na' -K' -ATPase enzyme, muscle glycogen and platelet distribution width, with the accuracy up to 97.39% in models. C5.0 algorithm showed that liver SDH activity was the most important hot or cold property, with the significance closed to 40%. It was followed by triglyceride, GOT, muscle glycogen and liver Na(+)-K(+)-ATPase enzyme, with the accuracy up to 98.26% in models. The possibilities that Evodiae Fructus is in hot property and Scutellariae Radix is in cold property were 100. 00% and 77.78% by using both C&R classification and regression algorithm and C5.0 algorithm.</p><p><b>CONCLUSION</b>The SDH activity of liver is the most important biological effect index to distinguish cold and hot properties of TCMs. The discrimination pathway or mode of cold and hot properties is closely related to energy metabolism.</p>