To enhance the quality and efficiency of ozagrel by investigating the differences between the ozagrel polymorphs in bioavailability. Solid ozagrel in different polymorph forms were orally administered to SD rats. An HPLC method was established to determinate plasma level of ozagrel. The bioavailabilities of two polymorph forms were calculated and compared. The pharmacokinetic parameters of ozagrel, were as follows: Cmax was 32.72 ± 17.04 and 34.01 ± 19.13 mg · L(-1), respectively; AUC0-t was 61.14 ± 14.76 and 85.56 ± 18.08 mg · L(-1) · h, respectively; t½ was 1.53 ± 0.51 and 4.73 ± 3.00 h, respectively. There was no significant difference in pharmacokinetic parameters between form I and II polymorphs of ozagrel while the t½ of form II is longer, which indicates that the use of form II polymorph as pharmaceutical product may prolong the effective action time in clinics. This would help the polymorph quality control in drug production.
Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Methacrylates ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Objective To explore the differences in the strength of the nodes in the brain white matter weighted networks between the male patients with paranoid schizophrenia and male healthy controls, and to analysis the integrity of the white matter fiber tracts that connected to the different brain regions and its relationship with the course of disease. Methods Diffusion tensor imaging (DTI) data were obtained from 25 male patients with paranoid schizophrenia and 26 male healthy controls. The whole brain was parcellated into 90 regions by using the anatomical label map. Tractography was performed in the whole brain of each subject to reconstruct white matter tracts using the FACT algorithm. The brain white matter weighted networks were then constructed using the complex network theory. Results The strength of the nodes in the networks of schizophrenia significantly decreased in the right thalamus (P=0.03, corrected) and the right hes?chl gyrus (P=0.04, corrected). Negative correlation was found between the strength of the right thalamus and the course of disease (r=-0.45, P=0.03). Conclusion The integrity of the white matter fiber tracts connected to the thalamus and tem?poral lobes in the male paranoid schizophrenia is impaired. The lesion of fiber tracts connected to the thalamus is related with the course of disease.

This study examined the expression of cell adhesion molecule 1 (CADM1) in pancreatic cancer and the possible mechanism. The expression of CADM1 was detected by immunohistochemistry in tissues of pancreatic cancer, pancreatitis, and normal pancreas. The plasmid pcDNA3.1-Hygro(+)/CADM1 was transfected into PANC-1 cells (a pancreatic cancer cell line). The expression of CADM1 in the transfected cells was determined by RT-PCR and Western blotting. Cell growth was measured by the MTT method and cell apoptosis by flow cytometry. The results showed that CADM1 was weakly expressed in tissues of pancreatic cancer in contrast to its high expression in normal pancreatic and pancreatitis tissues. The expression level of CADM in pancreatic caner was intensely correlated with the differentiation degree, lymph node metastasis and TNM stages. The growth of CADM1-transfected PANC-1 cells was significantly suppressed in vitro by a G1 cell cycle arrest and apoptosis occurrence. It was concluded that re-expression of CADM1 inhibits the growth of pancreatic cancer cells and induces their apoptosis in vitro. As a tumor suppressor gene, CADM1 plays an important role in the occurrence, progression and metastasis of pancreatic cancer.

OBJECTIVETo summarize the clinical application result of the selective nerve root blocks in limited operation of the lumbar spine.

METHODSFrom January 2008 to October 2012,68 patients with lumbar spinal canal stenosis with multiple levels were underwent the selective nerve root blocks in limited operation of the lumbar spine,including 47 males and 21 females with an average age of 56 years old ranging from 45 to 80. After never roots blocks,64 cases were positive for limited operation of the lumbar spine; the other 4 cases were negative and abort the operation.

RESULTSThe nerve roots block operation smoothly and no complications related to the nerve roots block occurred. There was no neurologic injury complication in this study. Follow-up period ranged from 16 to 45 months postoperatively (means, 32 months). The recovery effect was calculated with Macnab scores, the result was excellent in 44 cases, good in 18 cases, poor in 1.

CONCLUSIONOperative treatment for lumbar spinal canal stenosis with multiple levels is focused on the areas causing symptomate neural compression rather than prophylactic decompression at areas of nonsymptomatic disease. Application of selective nerve root blocks can accurately judge the responsible vertebral body and pain source and improve the curative effect of limited operation of the lumbar spine

Aged ; Aged, 80 and over ; Female ; Humans ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Nerve Block ; methods ; Spinal Nerve Roots ; Spinal Stenosis ; surgery

OBJECTIVETo summarize the clinical application results of the repair soft tissue defect in contralateral leg with a cross-leg soleus muscle flap pedicle transplantation.

METHODSFrom January 2008 to January 2013, 8 patients with soft-tissue defect in lower leg underwent reconstruction with a cross-leg soleus muscle flap pedicle transplantation (without microvascular anastomoses). There were 7 males and 1 female, aged from 20 to 49 years old with an average of 31.8 years. The operative time after injury was from 2 to 8 weeks with the mean of 46 days. The soleus muscle flap was transposed across to the contralateral leg defect area, then immediate to perform the coverage of the muscle flaps by a meshed split-thickness skin graft. The donor site was closed directly.

RESULTSAll the muscle flaps had survived completely. In one case, recipient area edge had a less exudate from drainage hole everyday, the incision spontaneously was healed after 2 week's changing dressing. Follow-up period ranged form 1.5 to 4 years with an average of 2.5 years postoperatively. The tibia and fibula fractures were healed well. A good contour was achieved at the recipient area. According to LEM standard, 2 cases got excellent results, 5 good and 1 fair.

CONCLUSIONSoleus flap pedicle transplantation is very suitable to repair the soft tissue defect of the injuried leg only one main blood vessel, and can reduce the damage of donor area.

Adult ; Female ; Humans ; Leg Injuries ; surgery ; Male ; Middle Aged ; Muscle, Skeletal ; Soft Tissue Injuries ; surgery ; Surgical Flaps

OBJECTIVETo investigate the regulatory effect of ligustrazine and Radix Astragalus (Chinese drugs for supplementing qi and activating blood circulation) on uterine mucosa stromal cyto-chemotactic factor RANTES and receptor CCR5 expression.

METHODSThe eutopic and ectopic endometrial stromal cells (EMSC) isolated and purified from 10 patients with ovarian endometrial cyst were selected as the experimental group, while those from 10 patients with benign lesion were selected as the control group. After they were intervened by different factors, including astragalus injection (AI), ligustrazine injection (LI), AI + LI, and Danazol, the expression levels of RANTES and CCR5 in the cells were detected by ELISA and RT-PCR.

RESULTSRANTES expressions in eutopic and ectopic EMSC were different insignificantly (P > 0.05). The ectopic EMSC RANTES expression was 13.602 +/- 3.358 ng/L and eutopic EMSC RANTES was 12.850 +/- 7.997 ng/L in the positive control group, which was significantly higher than that in the negative control group (both being 0.027 +/- 0.016 ng/L, P <0.05), and the ectopic EMSC expressions after intervened with Chinese drugs were significantly lower than that in the positive control group (P <0.05). CCR5 expression in ectopic EMSC was 0.759 +/- 0.039 ng/L, which was higher than that in eutopic EMSC (0.249 +/- 0.026 ng/L, P <0.05). Ectopic EMSC CCR5 expression was higher in the positive control group than that in the negative control group (0.759 +/- 0.039 ng/L vs 0.478 +/- 0.094 ng/L, P <0.05). Similar situation also was shown between the positive and negative control groups in terms of eutopic EMSC CCR5 expression (0.249 +/- 0.026 ng/L vs 0.131 +/- 0.021 ng/L, P < 0.01), and the expression was significantly lower in all the Chinese drugs treated EMSC groups as compared with that in the positive control group (P < 0.01).

CONCLUSIONCCR5 expression was higher in ectopic EMSC than that in eutopic EMSC. Ligustrazine and Radix Astragalus could down-regulate the auto-secretion of RANTES and CCR5 in patients with endometriosis.

Adult ; Astragalus Plant ; chemistry ; Cells, Cultured ; Chemokine CCL5 ; genetics ; metabolism ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Endometriosis ; drug therapy ; genetics ; metabolism ; pathology ; Endometrium ; cytology ; metabolism ; pathology ; Female ; Humans ; Pyrazines ; pharmacology ; Receptors, CCR5 ; genetics ; metabolism ; Stromal Cells ; drug effects ; metabolism

Objective To investigate the effects of tumor necrosis factor-alpha (TNF-α) on insulin sensitivity and glucose-lipid metabolism in TNF-α-induced IR mice. Methods Male C57BL/6J mice were given an intraperitoneal injection of TNF-α (H group,6μg/kg; M group,3μg/kg; L group,1μg/kg;twice daily) and saline (NC group) for 7 days. The plasma glucose and insulin were assayed during intravenous glucose tolerance test (IVGTT) and hyperinsulinemic-euglycemic clamp combined with 3-[3H] glucose as a tracer was carried out. Results After TNF-α treatment,fasting blood glucose (FBG),plasma insulin and free fatty acids (FFA) were significantly elevated in H group compared with NC,L and M groups (P<0.01 and P<0.05,respectively). There was a lower glucose tolerance in H group versus other three groups during IVGTT. The insulin release by glucose stimulation was higher in H group versus NC and L groups (P<0.01 and P<0.05). Basal glucose disappearance rate (GDR) and hepatic glucose production (HGP) were significantly increased in H group compared with NC group (P<0.01). During the steady-state of clamp,plasma insulin levels were significantly increased in H group versus NC group (341.7±17.7 vs 84.7±5.5mU/L,P<0.01). The suppressive effect of insulin on FFA was significantly blunted in H group compared with NC group (0.82±0.03 vs 0.43±0.07mmol/L,P<0.01). Steady-state glucose infusion rate (GIR) was significantly decreased in H group compared with NC group (39.1±2.3 vs 54.2±2.2 mg·kg-1·min-1,P<0.01). Although GDR was increased in both group,but it was still lower in H group than in control group(47.9±0.8 vs 53.9±2.0 mg.kg-1.min-1,P<0.01).As compared with baseline,HGP in the controls was almost completely suppressed during steady state of clamp,but in H group suppressed by approximately 41%. Conclusions High-dose TNF-α treatment induces the abnormality of glucose-lipid metabolism and the insulin resistance of hepatic and peripheral tissue in mice

The application of microsurgery and immunosuppressive agents have led to remarkable progress in uterus allotransplantation for patients with absolute uterine infertility. At present, more than 40 cases of human uterus transplantation have been successfully carried out worldwide, and 12 healthy newborn babies have been delivered using cesarean section. However, selection of transplant donors and recipient, in vitro uterine perfusion, the immunosuppressive therapy and characteristics of graft rejection after uterus allotransplantation are worthy of attention. This article reviews the research progress in uterus allotransplantation.

Roscovitine is a specific inhibitor of cyclin-dependent kinases (cdks) cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin E and cdk5/p35. The studies on the enzyme inhibitory properties and cellular effects of roscovitine revealed that it arrests cells in G(2)/M and G(1)/S phase, inhibits the proliferation of mammalian cells and induces cell death. However, the characteristics of cell death and exact mechanism by which this cdk inhibitor kills transformed cells are unknown. We previously investigated that the roscovitine induces apoptotic death of mitotic PC12 cells. The present study was to identify whether the roscovitine-induced death is related with the specific elements of caspases in pathway of apoptosis. The morphological data of caspase-3 immunofluorocytochemistry double staining with hoechst 33342 indicated that apoptotic nuclei were identified as nuclei with chromatin condensation and nuclear fragmentation, and that caspase-3 active p17 subunit co-existed in PC12 cells treated with roscovitine 50 micromol/L for 4 h. The number of the caspase-3 positive cells increased significantly to about 42%, as compared with the normal control (P<0.001). The data of MTT assay showed that the number of viable cells treated by roscovitine (50 micromol/L) alone for 12 h was 29.03%, of the untreated controls. Both a broad-spectrum caspase inhibitor Z-VAD-FMK (50 mumol/L) and a specific caspase-3 inhibitor Z-DEVD-FMK (100 micromol/L) increased viable PC12 cells to 45.16%, (Z-DEVD-FMK) and 58.06%, (Z-VAD-FMK), respectively, in the presence of roscovitine. Non-erythroid a-spectrin is a cytoskeleted protein that is a substrate of caspase-3 cysteine proteases. To confirm the activity of caspase-3 that produced in roscovitine (50 micromol/L for 12 h)-induced PC12 cell death, activated caspase-3 specific 120 kDa spectrin breakdown products (SBDP) were detected by Western bloting using the mouse anti-non-erythroid a-spectrin monoclonal antibody. The mean relative density of bands corresponding to caspase-3 specific SBDP levels were significantly increased in the cytosolic fractions treated with roscovitine, as compared to the normal control (P<0.001). These results indicate that caspase signals, especially caspase-3 signal are necessary for the progression of proliferating PC12 cell apoptotic death evoked by roscovintine.
Animals ; Apoptosis ; drug effects ; physiology ; Caspase 3 ; physiology ; Cyclin-Dependent Kinases ; antagonists & inhibitors ; PC12 Cells ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Rats

OBJECTIVETo explore clinical features, diagnostic methods and treatment of gallstone ileus.

METHODSClinical data of 5 patients with gallstone ileus were analyzed retrospectively. Pertinent literature from China between 2000 and 2009 were reviewed. The disease onset, clinical manifestations, imaging characteristics, diagnosis and treatment of gallstone ileus were studied.

RESULTSFour out of 5 patients were female aged over 60, of whom 3 had a previous history of cholelithiasis, 2 had a history of cholangiojejunostomy internal drainage procedure. Four patients underwent enterotomy and gallstone extraction combined with hepatobiliary operation, while one underwent enterotomy alone. There was no postoperative recurrence. A review of the literature from China revealed 441 cases with intestinal obstruction caused by gallstone, consisting 1.15% of all the cases with bowel obstruction. 67.12% were female. 73.56% were elderly. 87.92% were from cystoenteral fistula. Site of bowel obstruction in ileum was 64.17% of the cases. 71.89% were misdiagnosed with other types of obstruction. Two hundred twenty-five patients underwent enterotomy and gallstone extraction combined with hepatobiliary operation, which carried a lower rate of postoperative recurrence and malignancy (P<0.05) than enterotomy alone. There were no statistical significant differences in the occurrence of postoperative cystoenteral fistula, wound infection, pulmonary infection, cure rate, and mortality(P>0.05).

CONCLUSIONSThe incidence of gallstone ileus is low and more common in female elderly. The gallstones often drain through cystoenteral fistula and lodge in the ileum. Enterotomy without hepatobiliary operation is associated with potential risk of recurrence and development of gallbladder malignancy. Combined hepatobiliary operation is recommended in patients without significant comorbidities.

Aged ; Female ; Gallstones ; complications ; diagnosis ; surgery ; Humans ; Intestinal Obstruction ; diagnosis ; etiology ; surgery ; Male ; Middle Aged ; Retrospective Studies