Objective: To investigate the changes of ³¹P-MRS in denervated skeletal muscle at 7.0 T MR system. Methods: In the experiment group, a total of 18 male Sprague-Dawley rats aged 6-8 weeks old and weighing 200-250 g were obtained. The right posterior femoral nerve were transected, and the proximal stumps were ligated by using 5-0 nylon stitches to preclude spontaneous repair. A sham surgery (incision and exploration of the nerve) was performed at the same time (n=6). Before rat model established and at varying times after initial surgery (3 d, and 1, 2, 4, 6, and 8 weeks). ³¹P-MR spectra of rat quadriceps femoris were acquired on 7.0 T Agilent small animal MR imaging system. We quantified the phosphocreatine (PCr), adenosine triphosphate(β-ATP), and inorganic phosphate (Pi) using Creatine phosphate disodium salt(10 mmol/L) as an external standard. The ratios, include PCr/Pi, Pi/β-ATP, PCr/β-ATP, PCr/(PCr+Pi) and Pi/(PCr+Pi) were quantified in jMRUI. All data were analyzed by one way analysis of variance (ANOVA) with posttest inter-group comparisons using Bonferroni test. Comparative analysis methods between the experimental and control group were performed via independent samples t test. P<0.05 was considered as statistically significance. Results: The average measured concentrations of β-ATP, PCr, and Pi in control groups were (6.654±0.178) μmol/g, (25.656±0.738) μmol/g, and (1.594±0.096) μmol/g, respectively. There were significant statistically differences in β-ATP, PCr, Pi, PCr/Pi, PCr/PCr+Pi,Pi/PCr+Pi between the study and control group(P<0.05) at any measurement time point after denervation. Pi/β-ATP,PCr/β-ATP and pHi in the experimental group significantly statistically differed from those of the control group (all P<0.05)at each time point except on day 3 after operation. The total concentrations of β-ATP and PCr were reduced by 11.5% and 19.7% respectively on day 3. Thereafter, β-ATP and PCr declined rapidly by 63.1% and 68.8% at week 4 respectively, then decreased slowely by 74.0%和82.3% till week 10. The change of PCr/Pi is similar to β-ATP and PCr, but more remarkable. Pi, Pi/PCr+Pi, Pi/ATP showed a progressively increase till week 10. The intra-cellular pH (pHi) of normal rat muscles was 7.033±0.017, While the pHi gently in experiment rat muscles decreased during the entire experiment. Conclusion ³¹P-MRS with 7.0 T can quantify the temporal changes of energy metabolism and pHi in normal and denervated rat muscles. It shows that the dysfunction of energy metabolism are progressive with time and that they begin within a short period following the nerve section, the change of β-ATP, PCr, PCr/Pi take place primarily within 4 weeks after denervation. β-ATP, PCr, and PCr/Pi may be potential biomarkers of energy metabolism in the evaluation of denervated muscle atrophy.

To observe the effect of polydatin on proliferation and apoptosis of cervical cancer HeLa cells and explore its possible mechanism. The growth inhibitory effect was detected with MTT assay. After HeLa cells were treated with different concentrations (50, 100, 150 μmol•L⁻¹) of polydatin, MTT assay was used to detect the inhibitory effect of polydatin on proliferation of HeLa cells; Acridine orange/ethidium bromide staining was used for morphological changes in apoptotic HeLa cells； Annexin/propidium iodide staining was applied to detect HeLa cell apoptotic rate. In addition, flow cytometry was employed to analyze apoptosis and cell cycle distribution； RT-PCR and Western blot assay were used to detect PI3K, AKT, mTOR, and P70S6K mRNA and protein expression levels. The results showed that polydatin significantly inhibited HeLa cells proliferation in a dose-dependent manner. Polydatin can cause S phase arrest for HeLa cells, promote cell apoptosis and decrease the mRNA and protein expression levels of PI3K, AKT, mTOR and P70S6K. It indicated that polydatin could inhibit proliferation and induce apoptosis of cervical cancer HeLa cells, and the mechanism may be associated with inhibiting the PI3K/AKT/mTOR signaling pathway and suppressing downstream gene expression.

To observe synergistic effects of 999 Ganmaoling (GML) and its Chinese/Western materia medica (CMM and WMM) on pharmacodynamic action and to study underlying mechanisms, their anti-inflammatory, antipyretic effects were compared by assaying the increased capillary permeability induced by glacial acetic acid in mice, ear swelling induced by Xylene in mice, non-specific pleurisy induced by carrageenan in rats, and yeast induced fever in rats. Crystal violet (CV) and microbial activity (XTT) assay were used to evaluate the inhibition of GML and its CMM and WMM on KPN biofilm formation, and scanning electron microscopy (SEM) was applied for observing KPN biofilm morphology changes. The results showed that compared with control group, GML could reduce exudation amount of Evans-Blue and the degree of Ear swelling significantly, and CMM and WMM have no significant effects. The concentration of TNF-α and IL-1β of rat pleural effusion in GML, CMM and WMM group decreased significantly. The concentration of TNF-α, IL-1β and IL-8 in GML group, TNF-α, IL-8 in WMM group and IL-8 in CMM in rats serum decreased significantly. The body temperature in rats decreased significantly in GML and WMM group after 4-8 h of administration. CMM group showed no significant difference in rat body temperature compare with control. Compared with control group, GML (55-13.75 g•L⁻¹) could inhibit KPN biofilm formation and reduce number of viable cells in the KPN biofilm. CMM (45-22.5 g•L⁻¹) and WMM (10 g•L⁻¹) could also inhibit KPN biofilm formation and reduce number of viable cells (P<0.01). Result of SEM also showed that GML (55 g•L⁻¹) and its CMM (45 g•L⁻¹) and WMM (10 g•L⁻¹) could interfere the bacterial arrangement of KPN biofilm and extracellular matrix. GML and its CMM & WMM could inhibit the formation of KPN biofilm, CMM & WMM in GML showed synergism and complementation in inhibit KPN biofilm. Results showed that GML had obvious anti-inflammatory and antipyretic effects and could destruct KPN mature biofilm. WMM and CMM showed obvious synergistic effect against inflammation and inhibition of KPN biofilm formation and reduction of number of viable cells but no same effects against fever.

Objective To analysis the metabolic index among diabetic patients in community in summer and winter,and to provide evidence for disease management.Methods During June and December,119 diabetic patients were seleted from communities living for more than a year by the method of stratified cluster sampling.The metabolic indexes were compared usingpaired t test ,and the rate of biochemical indicators were analyzed by McNemar 's test between two seasons .Results The values of HbA1c,GLU and HDL -C were higher in winter than in summer (P <0.01).The mean values of TC in summer and winter were the same.The detection values of triglyceride and low density lipoprotein were lower in winter than in summer,but the difference was not statistically significant (P >0.05 ).The control rate of HbA1c was 56.36% in summer,and the control rate was 44.54% in winter,the difference was statistically significant (P <0.05).In summer, the control rate was 59.66%,higher than 45.38% in winter,and the difference was statistically significant (P <0.05). The control rate of blood pressure was better than that in winter,while triglyceride and low density lipoprotein control was better than that in summer,but which was not statistically significant (P >0.05).Conclusion The metabolic index of diabetic patients in Zhoushan urban community was significantly affected by seasonal changes.Most indexes were better in summer than that in winter,which suggested that the intervention of diabetics should be enhanced in winter.

Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stress-responsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment (TMEN). Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thorough and personalized.
Antineoplastic Agents ; therapeutic use ; CCAAT-Enhancer-Binding Protein-beta ; metabolism ; Humans ; Models, Biological ; Molecular Targeted Therapy ; methods ; trends ; NF-kappa B ; metabolism ; Neoplasms ; drug therapy ; metabolism ; Precision Medicine ; methods ; trends ; Signal Transduction ; drug effects ; Tumor Microenvironment ; drug effects

To develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric (LC-ESI-MS) method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis (CIA) rats. Glycyrrhetinic acid was used as the internal standard (IS). Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1% (V/V) formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring (SIM) mode. In normal and CIA rats, madecassoside (30 mg·kg(-1)) was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10-1 000 ng·mL(-1) with the square regression coefficient (r) of 0.998 9, while for madecassic acid, the linear range was 10-500 ng·mL(-1) with the square regression coefficient (r) of 0.996 1. The lower limit of quantification was 10 ng·mL(-1) for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between -0.95% and 6.30% for madecassoside and between -1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were > 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, cmax and AUC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA rats compared with normal rats. Along with repeated administration of madecassoside, the differences of pharmacokinetic parameters of both madecassoside and madecassic acid between CIA and normal rats gradually subsided. The pharmacokinetic characteristics of both madecassoside and madecassic acid in rats were significantly altered by arthritis status, and the differences of pharmacokinetic parameters between arthritis and normal rats coincide with the severity of arthritis.
Animals ; Antirheumatic Agents ; blood ; pharmacokinetics ; therapeutic use ; Area Under Curve ; Arthritis, Experimental ; drug therapy ; metabolism ; Arthritis, Rheumatoid ; drug therapy ; metabolism ; Centella ; chemistry ; Chromatography, Liquid ; methods ; Collagen ; Female ; Phytotherapy ; Plant Extracts ; blood ; pharmacokinetics ; therapeutic use ; Rats, Wistar ; Reference Values ; Severity of Illness Index ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods ; Triterpenes ; blood ; pharmacokinetics ; therapeutic use

Objective To develop a biological canulated screw and evaluate its mechanical properties, so as to provide theoretical basis for the bio therapy of fracture with enrichment technique of bone marrow stem cells, which could be diffused through the canula, particularly for promoting bone union of femoral neck fracture and preventing avascular necrosis of femoral head. Methods TC4 titanium alloyed canulated cancellous screw (7.3 mm in diameter) commonly used for internal fixation of femoral neck fracture was improved by designing an end sealing plug and side holes in a 900 mm-long canulated screw. The side holes were arranged along the axis of screw, and the first side hole was 20 mm away from the screw tip. The distance between each side hole was 10 mm, and the number of side holes ranged from 0 to 6. The screws without holes were tested as control, and the rest were divided into two groups, i.e., group A: force direction parallel to the side hole, group B: force direction perpendicular to the side hole. Three point bending test on the screw was conducted by using Instron material testing machine, so as to study the relationship between the mechanical strength of the screw and the number of side holes, and the loading direction. Results (1) When the force direction was parallel to the side hole, which was confined within 0, 1 or 2, the bending deformation of the screw reached 3 mm, and no differences were found in the maximum loads and elastic modulus of the screw. However, when the number of side holes was increased to 3 or more, a significant reduction in the maximum load and elastic modulus of the screw was found (P＜0.05). (2) When the force direction was perpendicular to the side hole, which was confined within 0,1 or 2, and the bending deformation of the screw reached 3 mm, no significant differences were found in the maximum loads of the screw. While no significant difference was found in the elastic modulus of the screw when the side hole was 0, 1, 2 and 3. With an increase in the number of side holes, the maximum loads (≧ 3 side holes) and elastic modulus (≧ 4 side holes) were significantly reduced (P＜0.05). (3) When the force direction was perpendicular to the side hole and the number of side holes was 3 or more, the maximum loads and elastic modulus of the screw were all significantly higher than the screw with the same number of side hole under force direction parallel to the side hole. Conclusions (1) For achieving better mechanical properties of the screw, the number of side holes in titanium alloyed canulated cancellous screw (7.3 mm in diameter) should be within 2; (2) If the number of side holes was equal or over 3, screws under force direction perpendicular to the side hole could provide better mechanical properties than screws under force direction parallel to the side hole. This study may provide some theoretical evidence and support for future clinical development and practice of the biological canulated screw.