Humans ; Neoplasm Metastasis ; pathology ; Neoplasm Staging ; methods ; Neoplasms ; classification ; pathology ; therapy

The DNA fragment sized 2 139bp, the same Sequence with AtKup1 gene from Arabidopsis thalianna was used as the templates for DNA family shuffling. The shuffeld AtKup1 gene library was expressed in the mutant of 5. cerevisae in which potassium transporter gene TRK1 and TRK2 were knocked out by homologous recombination. Then the screening was carried out in the low potassium media containing 5. 0 mmol/L KC1 and no histidine in it. it was found that both of diverse and wild AtKup1 gene can rescues the trk1△trk2△yeast mutant strain in low [ K + ] medium. The growth of 2 clones yeast containing diverse AtKup1 were beter than that of AtKup1 wild gene transformant. The sequencig results of the shuffeld AtKup1 showed that there were 2 nucleotide changed, which resulted in 2 amino acid variations in it compared with the original AtKup1. The potassium uptaking capacity of shuffled AtKup1 gene increased significantly when it was transformed into tobacco.

Objective To evaluate the value of ~(125)I permanent plantation in treating osseous metastases.Methods Twenty-two patients with osseous metastases were accepted radioactive seeds ~(125)I permanent plantation.The curative effect was appraised according to the degree of ostalgia relieving and the changing of the radiology imaging in patients.Results Accepted radioactive seeds ~(125)I permanent plantation,relief of pain was obtained and the effective rate is 91%(20/22).However none of the patients showed severe side-effect.Among 32 lesions in 22 cases followed-up by CT in 2 months,4 obtained CR, 18 obtained PR,10 NC and 0 PD.The responsive rate was 68.7%.Conclusion ~(125)I permanent plantation procedure can be a safe and effective method in treating osseous metastases and obtaining good clinical effects with minimal damage and few comnlications.

The purpose of this study is to investigate the function of a novel potassium transporter gene (NrHAK1) isolated from Nicotiana rustica roots using yeast complement and real-time PCR technique. The complementary DNA (cDNA) of NrHAK1, 2 488 bp long, contains an open reading frame (ORF) of 2 334 bp encoding a protein of 777 amino acids (87.6 kDa) with 12 predicted transmembrane domains. The NrHAK1 protein shows a high sequence similarity to those of high-affinity potassium transporters in Mesembryanthemum, Phytolacca acinosa, Arabidopsis thaliana, and so on. We found that the NrHAK1 gene could complement the yeast-mutant defect in K+ uptake. Among several tissues surveyed, the expression level of NrHAK1 was most abundant in the root tip and was up-regulated when exposed to potassium starvation. Moreover, the transcript accumulation was significantly reduced by adding 5 mmol/L NH4+ to the solution. These results suggest that NrHAK1 plays an important role in potassium absorption in N. rustica.
Cation Transport Proteins ; chemistry ; genetics ; physiology ; Plant Proteins ; chemistry ; genetics ; physiology ; Potassium ; metabolism ; Quaternary Ammonium Compounds ; pharmacology ; Sodium ; pharmacology ; Tobacco ; genetics ; metabolism

OBJECTIVETo evaluate the therapeutic effect of combined CT-guided percutaneous radio-frequency ablation (RFA) plus percutaneous ethanol injection (PEI) on nonresectable priminary hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE).

METHODSOne hundred fifty patients diagnosed as HCC either by pathology or by AFP combined with typical CT and angiographic image findings were studied, 99 men and 51 women, with an average of 51 years. Each patient had at least 3 lesions, ranging from 3.1 to 7.9 cm in diameter, average 5.0 cm. All patients were randomly divided into group A (control group) and group B (combination group) according to their check-in date (odd or even). In group A, 74 patients were treated with RFA alone two weeks after TACE. In group B, 76 patients were treated with RFA plus PEI two weeks after TACE.

RESULTSThe complete necrosis rate was 75.8% in group A and 89.5% in group B (P < 0.05).

CONCLUSIONThe clinical therapeutic effect of radiofrequency ablation (RFA) combined with percutaneous ethanol injection (PEI) is better than that of RFA alone after TACE in HCC.

Carcinoma, Hepatocellular ; therapy ; Catheter Ablation ; methods ; Chemoembolization, Therapeutic ; Ethanol ; administration & dosage ; Female ; Humans ; Liver Neoplasms ; therapy ; Male ; Treatment Outcome

OBJECTIVEThis study was to assess the influence of interaction of combination of immobilized nitrogen cycling bacteria (INCB) with aquatic macrophytes on nitrogen removal from the eutrophic waterbody, and to get insight into different mechanisms involved in nitrogen removal.

METHODSThe aquatic macrophytes used include Eichhornia crassipes (summer-autumn floating macrophyte), Elodea nuttallii (winter-growing submerged macrophyte), and nitrogen cycling bacteria including ammonifying, nitrosating, nitrifying and denitrifying bacteria isolated from Taihu Lake. The immobilization carriers materials were made from hydrophilic monomers 2-hydroxyethyl acrylate (HEA) and hydrophobic 2-hydroxyethyl methylacrylate (HEMA). Two experiments were conducted to evaluate the roles of macrophytes combined with INCB on nitrogen removal from eutrophic water during different seasons.

RESULTSEichhornia crassipes and Elodea nuttallii had different potentials in purification of eutrophic water. Floating macrophyte+bacteria (INCB) performed best in improving water quality (during the first experiment) and decreased total nitrogen (TN) by 70.2%, nitrite and ammonium by 92.2% and 50.9%, respectively, during the experimental period, when water transparency increased from 0.5 m to 1.8 m. When INCB was inoculated into the floating macrophyte system, the populations of nitrosating, nitrifying, and denitrifying bacteria increased by 1 to 2 orders of magnitude compared to the un-inoculated treatments, but ammonifying bacteria showed no obvious difference between different treatments. Lower values of chlorophyll a, COD(Mn), and pH were found in the microbial-plant integrated system, as compared to the control. Highest reduction in N was noted during the treatment with submerged macrophyte+INCB, being 26.1% for TN, 85.2% for nitrite, and 85.2% for ammonium at the end of 2nd experiment. And in the treatment, the populations of ammonifying, nitrosating, nitrifying, and denitrifying bacteria increased by 1 to 3 orders of magnitude, as compared to the un-inoculated treatments. Similar to the first experiment, higher water transparency and lower values of chlorophyll a, COD(Mn) and pH were observed in the plant+ INCB integrated system, as compared to other treatments. These results indicated that plant-microbe interaction showed beneficial effects on N removal from the eutrophic waterbody.

Biodegradation, Environmental ; Eutrophication ; physiology ; Magnoliopsida ; metabolism ; Nitrogen ; isolation & purification ; pharmacokinetics ; Systems Integration ; Water Microbiology ; Water Pollutants, Chemical ; isolation & purification ; pharmacokinetics ; Water Purification ; methods

Objective Sepsis is often accompanied by serious disorder of energy metabolism, which is characterized by high catabolism, leading to irreversible acute skeletal muscle decomposition. As a new sedative, dexmedetomidine can alleviate the hypercatabolism of sepsis to a certain extent, so it has the potential to improve acute skeletal muscle decomposition. The present work aims to investigate the effects of dexmedetomidine on the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.Methods Thirty-six male Sprague Dawley rats were randomly divided into three groups (n=12): control group(group CON),-model group(group LPS-CON) and intervention group(group LPS-DEX). The endotoxemic rat model was established by injecting lipopolysaccharide (LPS) intraperitoneally. After 24 hours intervention, the expressions of hypothalamic neuropeptide (POMC, CART, AgRP and NPY) mRNA as well as MuRF-1 and MAFbx mRNA in skeletal muscle in rats were detected by RT-PCR.Results Compared with control group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly up-regulated (P＜0.05), while the expression of AgRP mRNA was significantly down-regulated in-model group (P＜0.05). Compared with-model group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly down-regulated (P＜0.05), while the expression of AgRP mRNA was significantly up-regulated in intervention group (P＜0.05).Conclusion Dexmedetomidine could regulate the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.

BACKGROUNDAt present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.

METHODSThis study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.

RESULTSAt week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.

CONCLUSIONSCompared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.

REGISTRATION NUMBERChiCTR-TRC-13003776.

Adult ; Blood Glucose ; drug effects ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Combinations ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Metformin ; administration & dosage ; adverse effects ; therapeutic use ; Middle Aged ; Thiazoles ; administration & dosage ; adverse effects ; therapeutic use

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.
Adult ; Age Factors ; Alanine Transaminase ; blood ; Amlodipine ; pharmacokinetics ; pharmacology ; Antihypertensive Agents ; pharmacokinetics ; pharmacology ; Bayes Theorem ; Body Weight ; Calcium Channel Blockers ; pharmacokinetics ; pharmacology ; Humans ; Hypertension ; metabolism ; Metabolic Clearance Rate ; Middle Aged ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Renal Insufficiency ; metabolism ; Software

To explore the protective mechanisms of a novel molybdenum disulfide (MoS₂) nanozyme in alleviating inflammation-related endothelial cell injury by regulating mitochondrial dynamic, flower like-MoS₂ nanosheets were prepared by hydrothermal method, and its antioxidant enzyme-mimic activities were assessed via electron spin resonance (ESR) spectroscopy. It was shown that MoS₂ nanosheets had strong scavenging ability for hydroxyl radical (·OH) and singlet reactive oxygen species (¹O₂) in a dose-dependent manner. Using an in vitro lipopolysaccharide (LPS)-induced vascular endothelial cell injury model, the protective roles of MoS₂ nanozyme on cytotoxicity and apoptosis of endothelial cells were examined by MTT and Annexin V-FITC/PI assay, respectively. Mitochondrial fission/fusion of endothelial cell were observed by Mito-Tracker green probe. Reactive oxygen species (ROS) probe DCFH-DA and superoxide anion probe DHE were used to detect the level of oxidative stress in vitro. Plasmid GFP-LC3 transfection using colocalization analysis was applied to assess the autophagy of endothelial cells. The results showed that MoS₂ nanozyme could significantly reduce the cytotoxicity and apoptosis of endothelial cells stimulated by LPS, and prevent the impairment mitochondrial dynamics of endothelial cells, thus maintaining mitochondrial dynamics. In addition, MoS₂ nanozyme was also shown to alleviate LPS-mediated endothelial mitochondrial autophagy, thus protecting endothelial cells from inflammatory stress. These results established that MoS₂ nanozyme protected endothelial cells injury from inflammatory stress by regulating mitochondrial dynamics and mitochondrial autophagy of endothelial cells, which is expected to expand the use of MoS₂ nanozyme in the prevention and treatment of inflammation-related vascular endothelial diseases.