20-Hydroxytetraenoic acid induces hepatic fibrosis via the TGF-ß1/Smad3 signaling pathway.

Hepatic fibrosis is caused by excessive accumulation of extracellular matrix (ECM) due to repeated liver injury. Hepatic stellate cells (HSCs) play a key role in the pathogenesis and progression of hepatic fibrosis. A study showed that CYP4A14 gene defect can inhibit hepatic fibrosis, but the specific mechanism was not clear. In this experiment, patients with hepatic fibrosis, LX-2 cells (a human HSCs line), and mice with liver fibrosis induced by carbon tetrachloride (CCl4) were used to study the effect of 20-Hydroxytetraenoic acid (20-HETE), one of the main metabolites of arachidonic acid (AA) catalyzed by CYP4A enzyme, on hepatic fibrosis and its mechanism. Our experimental results showed that the 20-HETE of patients with hepatic fibrosis is significantly higher than that of normal people and is closely related to the degree of fibrosis. 20-HETE could induce activation of LX-2 cells and 20-HETE antagonist could inhibit the induction of 20-HETE. 20-HETE was significantly increased in CCl4-induced liver fibrosis mice and inhibition of 20-HETE production could attenuate hepatic fibrosis. 20-HETE induced hepatic fibrosis mainly via the TGF- ß1/Smad3 signal pathway. In conclusion, the results suggest that 20-HETE plays an important role in hepatic fibrosis and may be a possible target for the clinical treatment of hepatic fibrosis.

IL-8 exacerbates CCl4-induced liver fibrosis in human IL-8-expressing mice via the PI3K/Akt/HIF-1α pathway.

Liver fibrosis is an excessive accumulation of extracellular matrix (ECM) due to chronic liver injury. In recent years, the mechanism of liver fibrosis has been extensively studied. Hepatic stellate cells (HSCs) play an important role in the occurrence and development of liver fibrosis because activated hepatic stellate cells could synthesize a large number of ECM and thus participate in the process of liver fibrosis. Interleukin-8 (IL-8) (deletion in mice) is a versatile chemokine that promotes inflammation and affects cell growth by activating related pathways and plays an important role in the development and progression of a variety of diseases. Notably, the expression level of IL-8 was significantly higher in patients with liver fibrosis, suggesting that it may be related to the pathogenesis of liver fibrosis. In this study, we used hydrodynamic injection to deliver the lentiviral vector LV5-hIL-8 into mice. We found that hIL-8 could aggravate carbon tetrachloride (CCl4)-induced liver fibrosis through the PI3K/Akt/HIF-1α pathway. It is characterized by excessive accumulation of ECM as well as a significant increase in markers of liver injury. In addition, in PDGF-induced HSCs, we also demonstrated that hIL-8 could aggravate ECM accumulation through the PI3K/Akt/HIF-1α pathway. In conclusion, the results of this study on hIL-8 may help to identify potential targets for the clinical treatment of liver fibrosis.

Cigarette smoke extract combined with LPS reduces ABCA3 expression in chronic pulmonary inflammation may be related to PPARγ/ P38 MAPK signaling pathway.

ABCA3 (ATP-binding cassette class A3) is a transmembrane transporter that plays a positive role in chronic pulmonary inflammation by regulating lipid metabolism. However, it is not completely clear whether ABCA3 and its signaling factors are involved in chronic pulmonary inflammation induced by the combination of CSE (cigarette smoke extract) and LPS (lipopolysaccharide). In this study, we used the method of combining CSE and LPS which was widely used to study lung inflammation-related diseases and has been proven effective in our group's studies to create in vivo and in vitro pulmonary inflammation models. The result showed that, after CSE in combination with LPS treatment, ABCA3 expression was downregulated in rat lung in vivo and in a human alveolar cell line in vitro. ABCA3 expression was upregulated, and related inflammatory factors were downregulated in the state of overexpression of PPARγ or inhibition of the p38 MAPK pathway, while PPARγ deletion or MAPK14 overexpression showed the opposite results. The level of PPARγ remained unchanged, and the expression of ABCA3 was upregulated in the state of the p38 MAPK pathway was inhibited under overexpression of PPARγ. These results indicate that CSE combined with LPS can result in downregulation of ABCA3 under conditions of inflammation, and that the p38 MAPK signaling pathway mediated by PPARγ can regulate the expression changes of ABCA3, thus providing new targets for treating chronic pulmonary inflammation.

Pulmonary inflammation caused by cigarette smoke combined with lipopolysaccharide up-regulated OATP2B1 in rat lung tissue and pulmonary epithelial cells.

Organic anion transport polypeptide 2B1 (OATP2B1), as an uptake transporter, is involved in the transport of many related substrate drugs and endogenous substances in the lungs. A large amount of data shows that cigarette smoke plays an important role in the occurrence and development of lung diseases such as chronic obstructive pulmonary disease (COPD), asthma and bronchitis. However, the effect of cigarette smoke combined with lipopolysaccharide-induced pulmonary inflammation on the expression of OATP2B1 is not clear. In this study, we used cigarette smoke combined with lipopolysaccharide to establish a lung inflammation model in vivo and in vitro to explore the effect of inflammation on the expression of OATP2B1. Our study found that cigarette smoke combined with lipopolysaccharide-induced pulmonary inflammation upregulated the mRNA and protein expression of OATP2B1 and related inflammatory factors, and the expression level of related proteins was higher with the aggravation of inflammation. The experimental results of animals in vivo were consistent with those of cells in vitro. In summary, these findings provide a model and basis for a follow-up study of the mechanism of OATP2B1 in pulmonary inflammation.

[Analysis of correlation between maxillary molars and maxillary sinus mucosal thickening].

PURPOSE: To investigate the influence of maxillary molars on the thickening of maxillary sinus mucosa by cone-beam CT (CBCT). METHODS: A total of 72 patients with periodontitis were included in the study and 137 cases of maxillary sinus were evaluated using CBCT for the following parameters: location, tooth, maximal mucosal thickness, alveolar bone loss, vertical intrabony pockets and minimal residual bone height. The maxillary sinus mucosal thickness ≥2 mm was defined as mucosal thickening. The parameters that could influence the dimensions of the maxillary sinus membrane were assessed. The data were analyzed using univariate analysis and binary logistic regression by SPSS 25.0 software package. RESULTS: Mucosal thickening was present in 56.2% of 137 cases and increased in frequency as the alveolar bone loss of the corresponding molar progressed from mild (21.1%) to moderate (56.1%) to severe (69.2%), and the risk of maxillary sinus mucosal thickening increased by 6-7 times (moderate OR=7.13, 95%CI: 1.37-37.21; severe OR=6.29, 95%CI: 1.06-37.37). The severity of vertical intrabony pockets was correlated with the presence of mucosal thickness (no intrabony pockets 38.7%; type Ⅰ 63.4%; type Ⅱ 79.4%), with an increased risk of maxillary sinus mucosal thickening (type Ⅰ OR=3.72, 95%CI: 1.01-13.70; type Ⅱ OR=5.39, 95%CI: 1.15-25.30). The minimal residual bone height was negatively correlated with the presence of mucosal thickness(≤4 mm OR=99.00, 95%CI: 17.42-562.79). CONCLUSIONS: Alveolar bone loss, vertical intrabony pockets and the minimal residual bone height in maxillary molars were significantly associated with mucosal thickening of the maxillary sinus.

Cigarette smoke extract combined with LPS down-regulates the expression of MRP2 in chronic pulmonary inflammation may be related to FXR.

The transporter multidrug resistance protein 2 (MRP2) plays an important role in chronic pulmonary inflammation by transporting cigarette smoke and other related inflammatory mediators. However, it is not completely clear whether pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to MRP2 and its signal factors. In this study, CSE combined with LPS was used to establish an inflammation model in vivo and in vitro. We found that compared with the control group, after CSE combined with LPS treatment, the expression of MRP2 in rat lung tissue in vivo and human alveolar cell line in vitro was down-regulated, while the expression of inflammatory factors was up-regulated. Through silencing and overexpression of FXR, it was found that silent FXR could down-regulate MRP2 and up-regulate the expression of inflammatory factors. On the contrary, overexpression of FXR could up-regulate MRP2 and down-regulate the expression of inflammatory factors. Our results show that CSE combined with LPS can down-regulate the expression of MRP2 under inflammatory conditions, and the down-regulation of MRP2 expression may be achieved partly through the FXR signal pathway.

The changes of MRP2 expression in three kinds of pulmonary inflammation models: the downregulation occurred in cigarette smoke extract (CSE) stimulation group and CSE plus LPS stimulation group, unchanged in LPS stimulation group.

The transporter multidrug resistance protein 2 (MRP2) can transport some tobacco carcinogens and plays an important role in the transport of mediators related to pulmonary inflammatory diseases. However, it is not fully understood whether the pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to the regulation of MRP2. In this study, CSE and LPS were used alone and in combination as stimuli to induce pulmonary inflammation. In addition, the establishment of a pulmonary inflammation model was verified by animal experiments in vivo. We found that compared with those in the control group, the expression of MRP2 protein was downregulated and the expression of inflammatory cytokines was upregulated in pulmonary inflammation in the CSE group and the CSE combined with LPS group. However, there was almost no change in the expression of MRP2 stimulated by LPS alone. Our results show that CSE and CSE combined with LPS downregulate the expression of MRP2 under inflammatory conditions, while LPS has almost no effect on the expression of MRP2 under inflammatory conditions. The in vivo experimental results of CSE combined with LPS were consistent with the cellular results of CSE combined with LPS, which provides a model and basis for other studies of the role of MRP2 in pulmonary inflammation.

DJ-1 modulates Nrf2-mediated MRP1 expression by activating Wnt3a/ß-catenin signalling in A549 cells exposed to cigarette smoke extract and LPS.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by airway obstruction and abnormal inflammatory responses. Multidrug resistance-related protein 1 (MRP1) can reduce lung inflammation and damage by excreting various toxic exogenous substances and certain pro-inflammatory molecules. AIMS: We studied whether DJ-1 modulates nuclear factor erythroid 2-related factor 2 (Nrf2) by activating the Wnt3a/ß-catenin signalling pathway to further regulate MRP1 expression and pulmonary antioxidant defences in alveolar epithelial (A549) cells treated with smoke extract (CSE) and lipopolysaccharide (LPS). MAIN METHODS: Marker expression was studied by western blot analysis, quantitative real-time PCR and immunofluorescence staining of A549 cells. KEY FINDINGS: A549 cells exposed to CSE and LPS showed downregulation of DJ-1, Wnt3a, MRP1 and haem oxygenase-1 (HO-1) and upregulation of inflammatory factors. Additionally, Nrf2 protein levels were significantly decreased, while there was no change in Nrf2 mRNA levels. Overexpression of DJ-1 and Wnt3a activated Nrf2 signalling, increased MRP1 and HO-1 levels and decreased IL-6 protein expression, while knockdown of DJ-1 and Wnt3a had the opposite effects. Furthermore, DJ-1 overexpression and DJ-1 knockdown increased and decreased, respectively, the levels of Wnt3a and ß-catenin. Interestingly, Nrf2 and Wnt3a deficiency reduced the protective effects of Wnt3a and DJ-1, respectively, in A549 cells. However, the levels of DJ-1 and Wnt3a were not altered by Wnt3a and Nrf2 deletion, respectively. SIGNIFICANCE: In A549 cells treated with CSE and LPS, DJ-1 regulates Nrf2-mediated MRP1 expression and antioxidant defences by activating the Wnt3a/ß-catenin signalling pathway. These findings may provide potential therapeutic targets for COPD intervention.

Cigarette smoke extract combined with lipopolysaccharide reduces OCTN1/2 expression in human alveolar epithelial cells in vitro and rat lung in vivo under inflammatory conditions.

Organic cation transporter 1/2 (OCTN1/2) play important roles in the transport of drugs related to pulmonary inflammatory diseases. Nevertheless, the involvement of inflammation induced by cigarette smoke extract (CSE) combined with lipopolysaccharide (LPS) in the regulation of OCTN1/2 is not fully understood. In this study, CSE combined with LPS was used to establish inflammation models in vitro and in vivo. Our study found that the expression of OCTN1/2 was downregulated in rat lung in vivo and in a human alveolar cell line in vitro after treatment with CSE and LPS compared with the control group, while the expression of inflammatory factors was upregulated. After treatment with ipratropium bromide (IB) or dexamethasone (DEX), the expression of OCTN1/2 was upregulated compared with that in the CSE-LPS model group, while the expression of inflammatory factors was significantly downregulated. After administration of the NF-κB inhibitor PDTC on the basis of the inflammatory status, the expression of OCTN1/2 was upregulated in the treated group compared with the CSE-LPS model group, while the expression of phospho-p65, phospho-IκBα and inflammatory factors was significantly downregulated. We further added the NF-κB agonist HSP70 and found a result that the exact opposite of that observed with PDTC. Our findings show that CSE combined with LPS can downregulate the expression of OCTN1/2 under inflammatory conditions, and that the downregulation of OCTN1/2 expression may partially occur via the NF-κB signaling pathway.

LPS-induced inflammation delays the transportation of ASP+ due to down-regulation of OCTN1/2 in alveolar epithelial cells.

Organic cation transporters (OCTNs) can significantly affect drug disposition in alveolar epithelial cells (A549), but this process is not well understood. We investigated the expression and function of OCTN1/2 in A549 cells under different inflammatory status to examine pulmonary drug distribution. This experiment used lipopolysaccharide (LPS)-treated A549 cells to mimic inflammation in alveolar epithelial cells, and the expression of OCTN1/2, interleukin-6 (IL6), IL18, IL1ß and tumour necrosis factor-alpha (TNF-α) was investigated by western blot and quantitative real-time PCR (qRT-PCR). The fluorescent compound 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP+) was chosen as a probe to study the activity of OCTN1/2. OCTN1/2 down-regulation induced by LPS was more pronounced than that in normal control (NC) groups. Experiments further detected the release of inflammatory factors that revealed a negative correlation between OCTN1/2 expression and inflammation secretion in human alveolar epithelial cells exposed to different concentrations of LPS. The Michaelis constant (Km) and apparent permeability coefficient (Papp) of ASP+ were also decreased significantly. Our results thus show that LPS-induced inflammation could inhibit the expression and activity of OCTN1/2 in vitro and reduce the distribution of inhaled medicine in pulmonary diseases.

MiR-146a rs2910164 polymorphism and head and neck carcinoma risk: a meta-analysis based on 10 case-control studies.

Two recent meta-analyses have been conducted on the relationship between miR-146a polymorphism (rs2910164) and head and neck cancer (HNC) risk. However, they have yielded conflicting results. Hence, the aim of the present study was to conduct a quantitative updated meta-analysis addressing this subject. Eligible studies up to Sep 2016 were retrieved and screened from the bio-databases and then essential data were extracted for data analysis. Next, subgroup analyses on ethnicity, source of controls, sample size, and genotyping method were also carried out. As a result, a total of 9 publications involving 10 independent case-control studies were included. The overall data indicated a significant association between miR-146a rs2910164 polymorphism and HNC risk [C vs. G: odds ratio (OR) = 1.14; 95% confidence interval (CI) = 1.00-1.31; CC+CG vs. GG: OR=1.21; 95%CI=1.02-1.43]. Variant alleles of miR-146a rs2910164 may have a correlation with increased HNC risk. Future well-designed studies containing large sample sizes are needed to verify this result.

Switchable thulium-doped fiber laser from polarization rotation vector to scalar soliton.

We experimentally demonstrate switchable temporal soliton generation from a thulium-doped fiber laser (TDFL), using carbon nanotubes as the mode-locker. With the help of residual polarization dependent loss of a wavelength division multiplexer, a weak nonlinear polarization rotation (NPR) effect can be achieved within the laser cavity, which may provide joint contribution for passive mode-locking operation. By finely adjusting the polarization to alter the strength of NPR-based saturable absorption, the TDFL either approaches the operation regime of scalar soliton with strong NPR effect, or generates polarization rotation locked vector soliton (PRLVS) with weak NPR effect. The scalar solitons and PRLVSs possess 3-dB optical spectrum bandwidth of 2.2 nm and 2 nm, pulse-width of 1.8 ps and 2 ps, respectively. Moreover, the PRLVSs demonstrate a typical energy exchange between two polarized components on optical spectra and a period-doubling feature in time domain. Such operation principle can also be used in 1550 nm band fiber lasers and other nonlinear systems.

Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?: A meta-analysis based on 43 studies.

BACKGROUND: Previous reports showed that CYP2E1 RsaI/PstI polymorphism may be a risk factor for cancers. Published meta-analyses in 2010 and 2011, respectively, on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to head and neck carcinoma (HNC) have generated inconsistent results. Thus, this study aimed to conduct an updated meta-analysis involving published studies up to Nov 2015 to get a more confidential result. METHODS: Eligible studies up to Nov 2015 were retrieved and screened. Data were extracted and a quantitative meta-analysis was conducted. Subgroup analyses on ethnicity, source of controls, sample size, genotyping method, smoking status, and drinking status were also performed. RESULTS: Forty-one publications including a total of 43 case-control studies were selected for analysis. The overall data under a homozygote comparison model indicated a significant association of CYP2E1 RsaI/PstI polymorphisms with HNC risk (c2c2 vs c1c1: odds ratio [OR] = 1.97; 95% confidence interval [CI] = 1.53-2.53). Similar results were observed in the Asian subgroup (c2c2 vs c1c1: OR = 1.98; 95%CI = 1.51-2.60; c2 vs c1: OR = 1.20; 95%CI = 1.03-1.39) and mixed population (c2 vs c1: OR = 1.41; 95%CI = 1.06-1.86) when the data were stratified by ethnicities. Interestingly, increased cancer risk only was shown among never-smokers (c2c2+c1c2 vs c1c1: OR = 1.44; 95%CI = 1.05-1.98) but not ever-smokers. CONCLUSION: CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to HNC, particularly among Asians, mixed population, and never-smokers. Future large and well-designed studies are needed to verify this conclusion.

Luoyutong Treatment Promotes Functional Recovery and Neuronal Plasticity after Cerebral Ischemia-Reperfusion Injury in Rats.

Luoyutong (LYT) capsule has been used to treat cerebrovascular diseases clinically in China and is now patented and approved by the State Food and Drug Administration. In this retrospective validation study we investigated the ability of LYT to protect against cerebral ischemia-reperfusion injury in rats. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion followed by reperfusion. Capsule containing LYT (high dose and medium dose) as treatment group and Citicoline Sodium as positive control treatment group were administered daily to rats 30 min after reperfusion. Treatment was continued for either 3 days or 14 days. A saline solution was administered to control animals. Behavior tests were performed after 3 and 14 days of treatment. Our findings revealed that LYT treatment improved the neurological outcome, decreased cerebral infarction volume, and reduced apoptosis. Additionally, LYT improved neural plasticity, as the expression of synaptophysin, microtubule associated protein, and myelin basic protein was upregulated by LYT treatment, while neurofilament 200 expression was reduced. Moreover, levels of brain derived neurotrophic factor and basic fibroblast growth factor were increased. Our results suggest that LYT treatment may protect against ischemic injury and improve neural plasticity.

A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.

In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease.

MTHFR C677T polymorphism interaction with heavy alcohol consumption increases head and neck carcinoma risk.

MTHFR C677T polymorphism has been indicated to be a risk factor for cancers, but its association with head and neck cancer (HNC) risk remains inconclusive. In the present study, we aimed to get a more precise estimation by performing a quantitative meta-analysis. Published papers up to Jun 2014 was searched and screened. Necessary information was rigorously extracted for data pooling and analyzing, and then, subgroup analyses on ethnicity, source of controls, sample size, tumor type, smoking and drinking status were also carried out. As a result, twenty-three case-control studies including 14298 subjects were included. The overall data failed to reveal a significant association between MTHFR C677T polymorphism and HNC risk (homozygote comparison model: OR = 1.16; 95%CI = 0.93-1.45; dominant model: OR = 1.05; 95%CI = .90-1.21; recessive model: OR = 1.14; 95%CI = 0.93-1.38). However, in the subgroup analysis about drinking status, increase risk was shown in the heavy drinking subgroup (TT vs CC: OR = 3.11; 95%CI = 1.52-3.02). In conclusion, the results of the present study suggest that Homozygous TT alleles of MTHFR C677T polymorphism might be a risk factor for HNC among individuals who have a heavy drinking history. Further studies are needed to get a more definitive conclusion.

Hyaluronic acid/chitosan nanoparticles for delivery of curcuminoid and its in vitro evaluation in glioma cells.

The aim of this work was to evaluate the potential of polyelectrolyte complex nanoparticles (PENPs) based on hyaluronic acid/chitosan (HA/CS) as carriers for water-insoluble curcuminoid (CUR) and explore in vitro performance against brain glioma cells. PENPs were observed to be affected by the order of addition, mass ratios and initial concentrations of the HA/CS, pH and ionic strength. PENPs remained stable over a temperature range of 5­-55(C. CUR was successfully encapsulated into the PENPs. CUR-PENPs showed spherical shape with a mean diameter of 207 nm and positive charge of 25.37 mV. High encapsulation efficiency (89.9%) and drug loading (6.5%) was achieved. Drug release studies revealed initial burst release of drug from the PENPs up to 4h followed by sustained release pattern. DSC thermograms and XRD patterns showed that CUR was encapsulated inside the PENPs in a molecular or amorphous state. Compared with CUR-solution, CUR-PENPs showed stronger dose dependent cytotoxicity against C6 glioma cells and higher performance in uptake efficiency in C6 cells. Cellular uptake of CUR-PENPs was found to be governed by multi-mechanism in C6 cells, involving active endocytosis, macropinocytosis, clathrin-, caveolae-, and CD44-mediated endocytosis. In conclusion, CUR-PENPs might be a promising carrier for therapy of brain gliomas.

A pilot study on the correlation of tongue manifestation with the site of cerebral infarction in patients with stroke.

OBJECTIVE: To discuss the correlation of tongue manifestation with the site of cerebral infarction in patients with acute cerebral infarction. METHODS: From March 2008 to February 2009, 200 cases of hospitalized patients with first unilateral cerebral infarction were chosen in the Department of Neurology, Xuanwu Hospital. The correlation of different tongue color, fur texture, fur color with the site of cerebral infarction was analyzed. RESULTS: The site of cerebral infarction in patients were compared between different tongue color by Chisquare test (P=0.314), and further correspondence analysis demonstrated that there was correlation between red tongue and cortical-subcortical infarction group. The site of cerebral infarction in patients were compared between thick fur group and thin fur group, cortical-subcortical infarction occurred more frequently in the former (P=0.0008). The site of cerebral infarction in patients were compared between dry fur group, moist fur group and smooth fur group, correspondence analysis demonstrated there was correlation between dry fur and cortical-subcortical group. The site of cerebral infarction in the patients were compared between white fur group, white-yellow fur group and yellow fur group (P=0.010), and correspondence analysis demonstrated there was correlation between white fur and brainstem infarction; white-yellow fur has relationship with cortical infarction; subcortical infarction was weakly related with white-yellow fur; there was closer relationship between yellow fur and cortical-subcortical infarction. CONCLUSION: The change of tongue manifestation was associated with the site of cerebral infarction in patients, providing a new combining site for diagnosing cerebrovascular diseases by integrative medicine.

Pharmacokinetic Interaction of astragaloside IV with atractylenolide I and prim-O-glucosylcimifugin in male Sprague Dawley rats.

Astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin are main medicinal components of the traditional Chinese medicine prescription Yu-ping-feng which is composed of three herbs: Astragalus membranaceus, Atractylodes macrocephala, and Saposhnikovia divaricata. This study is aimed to assess the influence of atractylenolide I and prim-O-glucosylcimifugin on the pharmacokinetic profile of astragaloside IV so as to investigate the pharmacokinetic mechanisms of the Yu-ping-feng prescription. Fifteen Sprague Dawley rats were randomized to three groups; astragaloside IV, astragaloside IV plus atractylenolide I, and a combination of astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin were respectively administered to rats of these three groups via intragastric gavage. Serum samples were collected at different times after drug administration, and serum concentrations of astragaloside IV and atractylenolide I were simultaneously detected using HPLC-electrospray ionization-MS. Compared with administration of astragaloside IV alone, concentrations of astragaloside IV in the serum were significantly increased when it was given in combination with atractylenolide I or atractylenolide I+prim-O-glucosylcimifugin, with higher values for Cmax (p = 0.019 and p = 0.033 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively) and AUC (p = 0.0052 and p = 0.0047 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively). Improvement in mean oral Cmax and mean systemic serum exposure because of the pharmacokinetic interaction between astragaloside IV and atractylenolide I might explain the rationale for the use of multiple herbs in Yu-ping-feng and of combinations of A.membranaceus and A. macrocephala.