The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.
Acyl Coenzyme A ; metabolism ; Animals ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Hydrophobic and Hydrophilic Interactions ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; chemistry ; pharmacology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Medicine, Chinese Traditional ; Models, Molecular ; Quantitative Structure-Activity Relationship ; Technology

The cholesterol oxidase producing strain Brevibacterium sp.DGCDC-82 was treated with NTG (1 mg/mL)under ultrasonicztion(200 W,50 kHz).A red mutant named Brevibacterium sp.DGCCN-25 showed higher and stable production of cholesterol oxidase was obtained.The enzyme activity was increased by 140%,it is 1.24 U/mL.Then dealed with DGCCN-25 using the same method,two revertants were obtained,one was white and the other was rose pink.The enzyme activity of two revertants was obvious decrease,they are 0.17 U/mL and 0.69 U/mL.The results showed the positive correlation between COD acticity and red pigment producing by Brevibacterium sp..The relativity model can be used as a method of screening for mutation and directed evolution.

Objective To observe the clinical efficacy of intradermal needle plus acupoint application with Da Huang (Radix et Rhizoma Rhei) in preventing constipation after craniocerebral injury. Method Two hundred patients with acute craniocerebral injury were randomized into a treatment group and a control group, 100 cases each. The control group received conventional nursing care to prevent constipation, while the treatment group was additionally treated with intradermal needle plus acupoint application with Da Huang (Radix et Rhizoma Rhei). The occurrence of constipation within a week was observed in the two groups. Result The occurrence rate of constipation was 12.0％ in the treatment group versus 32.0％ in the control group, and the between-group difference was statistically significant (P<0.05). Conclusion Intradermal needle plus acupoint application can effectively reduce the frequency of constipation in patients with acute craniocerebral injury.

AIM: To explore correlation,consistency and comfort between traditional tear film examination methods and Oculus Keratograph.METHODS: A retrospective study.Totally 101 cases (101 eyes) were diagnosed myopia and then accepted LASEK (laser epithelial keratomileusis).Non-invasive tear film break-up time(NIBUT),lower tear meniscus height(LTMH) were measured with Oculus Keratograph,fluorescein tear film break-up time(fl-BUT) and Schimer Ⅰ test (SⅠt) were performed on all cases.The correlations analysis between NIBUT and fl-BUT,LTMH and SⅠt were performed by Spearman rank correlation,consistency check between NIBUT and fl-BUT by Bland-Altman analysis.Visual analogue scale(VAS) was applied on evaluating the comfort of two kinds of examination methods.RESULTS: LTMH and SⅠt showed positive correlation (rs=0.346,P=0.001).NIBUT and fl-BUT showed positive correlation (rs=0.393,P=0.001),95% consistency limits range-9.62 to 14.18 in Bland-Altman Figure.There was significant difference between VAS of NIBUT and VAS of fl-BUT(z=-2.324,P=0.020).There was significant difference between VAS of LTMH and VAS of SⅠt (z=-8.845,P=0.001).CONCLUSION: Oculus Keratograph can objectively measure NIBUT and LTMH,and was more comfortable than traditional tear film examination methods.It can effectively assess tear film function before corneal refractive surgery.

Objective To retrospectively study the biodistribution of 68Ga-DOTA-TATE as a SSTR imaging agent in human subjects.Methods A total of 106 patients with suspected disease were enrolled in this study.All patients were histologically proven for having either a single tumor ＜2 cm or without evidence of tumor during follow-up.Patients underwent PET/CT whole-body scan 17-100 min after intravenous injection of 55.2-220.0 MBq 68Ga-DOTA-TATE.ROI was drawn for measuring SUV of tracer-avid pathologies.One-way analysis of variance and two-sample t test were used for statistical analysis.Results High 68Ga-DOTA-TATE avidity was found in pituitary,with SUVmax of 4.00± 1.21.Tracer was excreted mainly through urinary system resulting in highest uptake in the urinary tracts.The SUVmax of kidney cortex was 19.01 ± 5.45.Mediastinal blood pool and liver SUVmax were 0.93±0.33 and 7.69±2.26,respectively.Mild uptake of 68Ga-DOTA-TATE was found in the brain,cerebellum,lung and muscle,all lower than that of mediastinal blood pool.Moderate accumulation of 68 Ga-DOTA-TATE (close to or slightly higher than liver) was found in adrenal gland and spleen,with SUVmax 7.61 ± 3.42 and 8.63± 2.31,respectively.Other organs (pituitary,salivary gland,thyroid,pancreas,small intestine,colon,uterus,prostate and bone) showed tracer uptake in the range between those of mediastinal blood pool and liver.68Ga-DOTA-TATE distribution in pancreas was not uniform.Nine patients had focal accumulation in the uncinate process of pancreas with highest SUVm~ up to 8.48.However,the SUVmax and SUV in the rest of pancreas (head,neck,body and tail) showed insignificant difference (F values:0.703,0.563,both P＞0.05).68Ga-DOTA-TATE uptake in each organ reached equilibrium quickly after injection but with slight increase over time.The changes in SUV,however,showed insignificant difference among organs,including different parts of pancreas (t values:from -0.09 to 1.75,from-1.70 to-0.42,respectively,all P＞0.05).Conclusions The biodistribution of 68Ga-DOTA-TATE reaches equilibrium shortly after intravenous administration and is stably maintained.The biodistribution activities are organ-specific,and characteristic to that of SSTR concentration.

Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.
Cholesterol Ester Transfer Proteins ; antagonists & inhibitors ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; Molecular Docking Simulation

Based on our previous electrical heart model, an electromechanical biventricular model was constructed by means of composite material theory and the finite element method. And the 3-D motion of the right ventricular wall was simulated based on this model. The orientation of cardiac fibers and myocardial contractility were taken into consideration during simulation modeling. The propagation of electrical excitation was simulated using an electrical heart model, and the resulting active forces was used to calculate the ventricular wall motion. Regional deformation and Lagrangian strain tensors were calculated during systole. Displacements, minimum principal strains were used to describe the motion of the right ventricle. The simulation results are in good accordance with results obtained from MR tagging images reported in literatures. In addition, the results also show that although the maximum displacement occurs in the base of the heart, however, the maximum contraction occurs in the apex of the heart. Such result is very difficult to be obtained by means of animal experiment or human experiment. This study suggests that such electrophysiologic-mechanical biventricular models have the important significance to be used to assess the mechanical functions of the two ventricles.
Computer Simulation ; Electrophysiology ; Finite Element Analysis ; Humans ; Imaging, Three-Dimensional ; Models, Cardiovascular ; Movement ; Myocardial Contraction ; physiology ; Ventricular Function, Right ; physiology

Objective: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic tumors and the relevant complications. Methods: A total of 343 patients with 778 hepatic tumors underwent ultrasound-guided RFA (582 procedures). There were 212 cases of hepatic cellular carcinoma (HCC) with 448 tumors, and the average largest diameter was 4.0 cm.Of all the patients, 63 (29.7%) were in the stage of Ⅰ-Ⅱ(UICC Systems) and 149 (70.3%) in stage of Ⅲ-Ⅳ(including 43 patients with tumor recurrence after surgical resection). There were 131 cases of metastatic liver carcinoma (MLC), with 330 metastases in the liver, the average diameter was 3.9 cm, and the liver metastases of 91 patients (69.5%) came from gastrointestinal tract. The patients were treated using the relatively standard protocol. Crucial attention must be paid to monitoring the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structure injury in time. The tumors were considered ablated successfully if no viability was found on enhanced CT within 24 hours or 1 month after RFA. The patients were followed up for 2 -62 months.Results: The ablation success rate for HCC was 95.5% (428/448 tumors), and the rate for MLC was 96.4% (318/330 tumors). The local tumor recurrence rates for HCC and MLC were 8.5 % (38/448 tumors) and 11.8 % (39/330 tumors), respectively. A total of 138 patients (40.2%) underwent repeated ablations for 2-11 times because of tumor recurrence or metastasis. The first,second and third years survival rates were 87.7% , 67.4% and 56.8% for HCC patients, 81.6%, 50.8% and 27.2% for MLC patients,respectively. The survival rate from 63 early-stage HCC patients were 92.9%,82.8% and 74.5%, respectively. The major complication rate in this study was 2.4 % (14 of 582 procedures).The complications which consisted of mechanical and thermal injuries usually occurred during or shortly after the RFA treatment. There were 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages and 1 skin burn. Conclusion: RFA, as a minimally invasive local treatment, has become an effective and relatively safety alternative for the patients of hepatic tumors, even of advanced live tumor, tumor recurrence, liver metastases which are unresectable or difficult to treat with traditional therapies. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.

To prepare doxorubicin-loaded N-octyl-N'-succinyl chitosan polymeric micelle (DOX-OSC) and study the biodistribution of DOX-OSC in mice, DOX-OSC was prepared by dialysis method. By using doxorubicin injection (DOX-INJ) as control, DOX-OSC and DOX-INJ were administered to mice through caudal vein at a dose of 5 mg x kg(-1) body weight. The RP-HPLC method was established to determine the DOX levels in the plasma and other tissues of mice. The tissues distribution and targeting efficiency were evaluated by pharmacokinetic parameters (AUC, MRT) and targeting parameters (Re, Ce and Te). The drug loading and entrapment efficiency of DOX-OSC were (35.8 +/- 0.4)% and (75.3 +/- 1.1)%, respectively. The diameter and zeta potential of DOX-OSC were (174 +/- 12) nm and (-37.1 +/- 3.0) mV, respectively. The transmission electron microscope result showed DOX-OSC with spherical shape. The biodistribution results showed that the concentration of DOX of both DOX-OSC and DOX-INJ decreased rapidly in blood after iv administration. While free DOX levels in blood at 12-96 h were not detectable for DOX-INJ, in contrast, DOX level in blood at 96 h was still found for DOX-OSC. In contrast to DOX-INJ group, DOX-OSC showed a higher targeting efficiency in the liver and spleen. The AUCs of DOX in the liver and spleen were 20.0 and 47.4 times and the MRT were 11.2 and 37.2 times, respectively. And the levels of DOX-OSC in the heart and kidney tissues were significantly reduced. And the drug distribution of DOX-OSC in the heart and kidney tissues were 17.0% and 11.4%, respectively. Hence, DOX-OSC shows an excellent drug loading capabilities and a higher targeting efficiency in the liver and spleen. That the levels of DOX-OSC in the heart and kidney tissues are significantly reduced, might improve the treatment efficacy of DOX and decrease the side effects.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Chitosan ; analogs & derivatives ; chemistry ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Female ; Liver ; metabolism ; Male ; Mice ; Micelles ; Particle Size ; Polymers ; Spleen ; metabolism ; Tissue Distribution

Objective To explore the effect of folic acid and DNA methyltransferase 1 (DNMT1) on cervical cancer and cervix precancerous lesion. Methods 100 patients with cervix squamouscell carcinoma (SCC), 101 patients with cervical intraepithelial neoplasm (CIN) and 109 patients with cervix inflammation (CI) diagnosed by histology were included in this study. Radioimmunoassay (RIA), polymerase chain reaction (PCR) and Western blot were used to detect the levels of serum folate, HPV16 infection and the expression of DNMT1 protein,respectively. Results The average levels of serum folate were (2.60 ± 1.61) ng/ml, (3.14 + 2.08) ng/ml and (3.32+1.74) ng/ml,and the expression of DNMT1 protein were 2.40 + 0.99,1.88 + 0.33 and 0.89 ± 0.29 in the group of SCC, CIN and CI, respectively.The relationship of folate levels and DNMT1 protein expression showed inverse correlation (r=-0.186, P=0.00l). The results in our study indicated that there was an additive interaction between low-level of serum folate and high-expressionof DNMT1 protein related to the risk of CIN and SCC, with OR value as 2.50(95%C/: 1.21-9.22) and 6.03 (95%C/: 2.79-21.72) respectively. The relative excessrisk of interaction (RERI) , attributableproportion of interaction (API) and synergy index (S) were 0.92, 0.36 and 2.59 in the CIN group while 2.47, 0.41 and 1.96 in the SCC group. Conclusion The low level of serum folate and high expression of DNMT1 protein seemed to be associated with high risk of cervical cancer and its precancerous lesion. It suggested that there might be a synergistic action between serum folate and DNMT1 in the progression of cervix carcinogenesis.