Animals ; Bone Neoplasms ; pathology ; Cell Adhesion ; Cell Culture Techniques ; methods ; Coculture Techniques ; Drug Screening Assays, Antitumor ; methods ; Humans ; Neoplasm Invasiveness ; Tumor Cells, Cultured

OBJECTIVETo investigate the ultrastructural variation of the facial nerve of rabbit with different dosage of (125)I seed brachytherapy.

METHODSFifty-four big ear rabbits were divided into 3 groups randomly and given 40 Gy, 80 Gy, 120 Gy respectively. Radioactive seeds were implanted in one side of parotid gland, the other side was implanted with vacant shell as a control group. The facial nerves were obtained 2, 4, 6 months respectively after operation and the histological ultrastructural changes observed by electromicroscope.

RESULTSIn the control group, epineurium was continuous, there was slight pitting edema under the epineurium, and axonal myelin was loose. In the test groups, there was slight pitting edema under the epineurium, and axonal myelin sheath was loose at 4th month. Macrophage and regenerated fibers were found in the 80 Gy group and myelin sheath lamellar separation, regeneration of nerve in the 120 Gy dosage. The myelin sheath lamellar was separated and axonal myelin loose in the test group at 6th month. Myelin sheath amellar separation and edema under the epineurium were found in the group of 80 Gy and 120 Gy.

CONCLUSIONSThe ultrastructure of the facial nerve is damaged by the dosage of 40 Gy, 80 Gy brachytherapy with (125)I seeds. The higher dosage the nerve receives, the more serious the damage will be. Both of the epineurium and axonal myelin sheath are integral and continuous 6 months after operation with dosage of 120 Gy.

Animals ; Brachytherapy ; Dose-Response Relationship, Radiation ; Facial Nerve ; radiation effects ; ultrastructure ; Female ; Iodine Radioisotopes ; administration & dosage ; radiation effects ; Male ; Rabbits ; Radiation Injuries, Experimental ; pathology ; Random Allocation

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

OBJECTIVETo study the action characteristics of "two-way application and conditioned dominance" of traditional Chinese medicines with neutral property by observing the action characteristic of 10 traditional Chinese medicines capable of promoting blood circulation and removing blood stasis with neutral property in the microcirculation in rats with heat stagnation and blood stasis syndrome.

METHODThe rat model with heat stagnation and blood stasis syndrome was established by injecting carrageenan and dry yeast, and the rat model with cold stagnation and blood stasis syndrome was built by the body freezing method. Ten traditional Chinese medicines with neutral property, including 5 with hot property and 5 with cold property, were selected for intervention to observe blood flow rate and flow state indicators in rat auricles and make a comparative analysis on action characteristics of traditional Chinese medicines with neutral property.

RESULTANOVA showed that among the 10 traditional Chinese medicines with neutral property, 6 such as Typhae Pollen, Sappan Lignum and Vaccariae Semen can obviously increase the blood flow rate (P < 0.01 or P < 0.05) in the above two models; all of the 5 traditional Chinese medicines with cold property can increase the blood flow rate (P < 0.01 or P < 0.05) in the rat model with heat stagnation and blood stasis syndrome, but only Salvia miltiorrhiza can increase the blood flow rate (P < 0.01 or P < 0.05) in the rat models with cold stagnation and blood stasis syndrome, while other medicines showed no notable effect; among the 5 traditional Chinese medicines with hot property, Carthamus tinctorius and Ligusticum chuanxiong can increase the blood flow rate (P < 0.01 or P < 0.05) in the rat models with cold stagnation and blood stasis syndrome, but had no obvious effect to the blood flow rate in the rat models with heat stagnation and blood stasis syndrome. According to the analysis on average blood flow rate, traditional Chinese medicines with natural and cold properties showed similar effect on heat stagnation and blood stasis syndrome and better effect in increasing blood flow rate than those with hot property; those with natural and hot properties showed similar effect and better effect in increasing blood flow rate than those with cold property.

CONCLUSIONUnder the condition of heat stagnation and blood stasis syndrome, traditional Chinese medicines with neutral property have the similar action characteristics with those with cold property; wile under the condition of cold stagnation and blood stasis syndrome, traditional Chinese medicines with neutral property have the similar action characteristics with the Chinese medicinal herbs with hot property. This indicates the action characteristics of "two-way application and conditioned dominance" of traditional Chinese medicines with neutral property to some extent.

Animals ; Blood Circulation ; drug effects ; Blood Coagulation ; drug effects ; Male ; Medicine, Chinese Traditional ; Microcirculation ; drug effects ; Rats ; Syndrome

OBJECTIVETo further study the characteristics of drugs with neutral property in two-way application and conditioned dominance by observing the action characteristic of 10 traditional Chinese medicines with neutral property in hemorheological indicators of heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome rats.

METHODThe model of heat stagnation and blood stasis syndrome rats was established by injecting carrageenan and dry yeast, while the model of cold stagnation and blood stasis syndrome rats was established by body freezing. Subsequently, 10 traditional Chinese medicines with neutral property, 5 traditional Chinese medicines with heat property and 5 traditional Chinese medicines with cold property were selected for intervention to observe the changes in such indicators as whole blood viscosity, plasma viscosity and hematocrit and analyze the action characteristics of drugs with neutral property.

RESULTANOVA showed that among six of the 10 traditional Chinese medicines with neutral property, including Typhae Pollen, Sarcandrae Herba and Sappan lignum, could obviously increase the hemorheological indicators of both heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome rats; five traditional Chinese medicines with cold property, such as Salviae Miltiorrhizae Radix et Rhizoma, Leonuri Herba, Rhei Radix et Rhizoma, could significantly ameliorate the hemorheological indicators of heat stagnation and blood stasis syndrome rats (P < 0.01 or P < 0.05), and Salvia Miltiorrhiza Radix et Rhizoma alone could ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats (P < 0.05); all of the five traditional Chinese medicines with heat property could significantly ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats (P < 0.01), among which Carthami Flos and Notoginseng Radix et Rhizoma could significantly ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats. According to the average high-shear blood viscosity analysis, drugs with neutral property showed similar action characteristics to those with cold property in ameliorating hemorheology indicators of heat stagnation and blood stasis syndrome rat and better effect than those with heat property in reducing whole blood viscosity; and traditional Chinese medicines with neutral property have the similar action characteristics to those with heat property in improving the hemorheology indicators of cold stagnation and blood stasis syndrome rat and better effect than those with heat property in reducing whole blood viscosity.

CONCLUSIONUnder the condition of heat stagnation and blood stasis syndrome, traditional Chinese medicines with neutral property show the similar action characteristics to those with cold property; but under the condition of cold stagnation and blood stasis syndrome, traditional Chinese medicines with neutral property show the similar action characteristics to those with heat property. This indicates that traditional Chinese medicines with neutral property show both heat and cold properties under he conditions of heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome.

Analysis of Variance ; Animals ; Blood Circulation ; drug effects ; physiology ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Hemorheology ; drug effects ; Homeostasis ; drug effects ; Male ; Medicine, Chinese Traditional ; methods ; Rats ; Rats, Sprague-Dawley ; Thrombosis ; drug therapy ; physiopathology

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Injections, Epidural ; Intervertebral Disc Displacement ; complications ; drug therapy ; physiopathology ; prevention & control ; Low Back Pain ; complications ; drug therapy ; Lumbar Vertebrae ; injuries ; Male ; Middle Aged ; Pharmaceutical Preparations ; administration & dosage ; Recovery of Function ; Recurrence ; Time Factors ; Treatment Outcome

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

OBJECTIVETo evaluate clinical outcomes after laparoscopic total mesorectal excision (TME) combined with intersphincteric resection (ISR) for ultra-low rectal tumors.

METHODSClinical data of 36 patients with ultra-low rectal tumor undergoing laparoscopic TME combined with ISR were analyzed retrospectively.

RESULTSThe median distance from the inferior margin of the tumor to the anal verge was 3.4 (2.0-5.0) cm. There were 33 cases of well/moderately differentiated adenocarcinoma and 3 rectal malignant villous adenoma. There were 16 patients with stage I disease, 15 with stage II A, 3 with stage III A, and 1 with III B. Postoperatively, one patient developed stenosis at the end ileostomy and 3 anastomotic leakage. After a median follow-up of 16(4-49) months, one patient developed local recurrence at the anastomosis and one case died of liver metastasis. In the 19 patients who had a minimum follow-up of one year, the bowel movements frequency ranged from 1-4 times per day, and these patients were able to withhold defecation for more than 5 minutes.

CONCLUSIONSLaparoscopic TME combined with ISR can achieve oncologic clearance, sphincter preservation, and minimal invasiveness for ultra-lower rectal cancer. However, patients selection should be cautious.

Adult ; Aged ; Aged, 80 and over ; Anal Canal ; surgery ; Female ; Follow-Up Studies ; Humans ; Laparoscopy ; Male ; Mesentery ; surgery ; Middle Aged ; Rectal Neoplasms ; surgery ; Rectum ; surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo explore the relationship between the expression of Survivin and Ki67 with prognosis of pancreatic endocrine tumors (PETs).

METHODSImmunohistochemistry for Survivin and Ki67 was performed in 25 cases of normal pancreatic tissues and 81 cases of PETs by tissue microarrays and to observe the expression and evaluate the relationship with prognosis.

RESULTS(1)The expression of Survivin and Ki67 in PETs was significantly higher than that in normal pancreatic tissues (P <0.01); (2)The expression of Survivin and Ki67 in PETs was correlated with tissue grading and the TNM-staging (P < 0.05), but not related with tumor size, location and functional status. In addition, the expression of nuclear Survivin was association with lymph node metastasis (P < 0.05). (3)The high expression of Ki67 was related with the expression of nuclear Survivin, but not related with the expression of cytoplasmic Survivin.

CONCLUSIONSurvivin and Ki67 were both expressed in PETs, which were closely related to the clinical pathological characteristics. They could be used as new indicators in the evaluation of prognosis of PETs. The expression of Survivin in nucleus had more diagnostic significance than that in cytoplasm, and that could be highly correlated with lymph node metastasis, which would be used as a new marker of poor prognosis.

Biomarkers, Tumor ; metabolism ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; metabolism ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Neoplasm Staging ; Pancreatic Neoplasms ; diagnosis ; Prognosis

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
Animals ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; HEK293 Cells ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lactates ; pharmacology ; Organic Anion Transporters ; metabolism ; Rats ; Rosuvastatin Calcium ; pharmacology ; Solute Carrier Organic Anion Transporter Family Member 1b1