Objective To study the effect of once-weekly injection of recombinant human parathyroid hormone rhPTH(1-34) on the healing of bone fracture in rats.Methods Fifty male 3-month old SD rats were used in this study to produce unilateral tibial fracture and received internal fixation with a Kirschner needle.Based on the dose and frequency of rhPTH (1-34) injection, the rats were randomly divided into five groups (n=10 each) as follows: subcutaneous injec-tions of saline, and rhPTH in a dose of 10, 20, 10, and 20 μg/kg/d.After 4 weeks of treatment, the rats were euthana-tized and the fractured tibia were assessed by X-ray, dual energy X-ray absorptiometry ( DXA) ,micro-computed tomography ( microCT) and three-point bending test.Results The fracture healing in the 20μg/kg/w group was better than the saline group.The fracture healing in the 20μg/kg/w group was as well as the 10 μg/kg/dgroup.The BMD of 20μg/kg/w group was 26.2%higher than the saline group.The mineralized callus volume in the 20μg/kg/w group was 51.4%higher than the saline group.The total callus volume in the 20μg/kg/w group was 21.6%higher than the saline group.The ultimate load of the 20 μg/kg/w group was 29.3% higher than the saline group.There was no significant difference between the 20 μg/kg/w group and 10 μg/kg/d group in BMD, bone micro-architecture, and biomechanical strength ( P >0.05 ) . Conclusions Once weekly injection of rhPTH (1-34)can promote the bone fracture healing.

OBJECTIVETo explore the effect of combined preoperative chemotherapy with radiotherapy on locally advanced lower rectal carcinoma.

METHODSThirty- five patients with locally advanced lower rectal carcinoma were received a new regimen of combined preoperative chemotherapy with radiotherapy. Routine fr action of radiation was given with total dose of 46 Gy,2 Gy per fraction,five ti mes a week. Patients received oxaliplatin 130 mg/m(2) (infusion) on day 1, plus leu novorin 200 mg/m(2) and 5- FU 500 mg/m(2)(intravenous bolus) from day 1 to day 3 eve ry 3 weeks for total two cycles before irradiation. Operation was performed 4 to 6 weeks later after neoadjuvant therapy.

RESULTSAfter neoadjuvant therapy,all patients underwent surgical resection with complete pathologic response in 7 patients,average tumor size decrease of in 34.4%, tumor stage decrease in 65.7% o f patients and nodal- negative change rate of 55.6%. Radical resection was per formed in 34 patients,in whom 18 patients received abdominoperineal resection(AP R) and 16 patients received sphincter- preserving surgery with 45.7% of anal preservation rate. One patient received palliative resection. No local recurrence occurred in all patients who received radical resection,but two cases had liver metastasis.

CONCLUSIONCombined preoperative chemotherapy with radiotherapy is a better neoadjuvant therapy for lower advanced rectal cancer,which can decrease tumor stage,improve resectability and anal sphincter preservation rate,therefore ,this new neoadjuvant therapy with tolerable toxicity will has a promising application in the clinical setting.

Adult ; Aged ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; pathology ; surgery ; therapy ; Treatment Outcome

OBJECTIVE: To investigate the effect of form-deprivation on level of gelatinase in the posterior sclera in chicks. METHODS: Fifty 1-day-old chicks were monocularly deprived to establish the animal model of form-deprivation myopia (FDM). According to the duration of form-deprivation the experimental chicks were divided randomly and equivalently into 5 groups, which were deprived for 3, 7, 14, 21 and 30 days respectively. Meanwhile the other eyes of the deprived chicks were used as self-control groups and chicks of the same days were chosen randomly as the normal control groups for each FDM group. At each form-deprivation point the changes of degree of diopters and axial length of chicks in each group were recorded. The levels of gelatinase in posterior sclera of the experimental eyes were measured by gelatin enzymography. RESULTS: Compared with the normal and self-control groups, the levels of MMP-2 activity in FDM groups were much higher (P <0.01). With the increase of the time of monocular deprivation these changes became more significant and reached the top after 14 days' deprivation with an inter-group statistical difference (P <0.01). The dynamic changes of MMP-2 activity were the same as those of axial length and degree of diopters in each experimental groups. There was positive correlation between the MMP-2 activity and axial length (r = 0.989, P < 0.01). But there was a negative correlation between the MMP-2 activity and refractive degree. CONCLUSION Increase of MMP-2 activity in the posterior sclera of chicks would be a direct key factor to trigger sclera ECM remodeling process in chick FDM.
Animals ; Chickens ; Gelatinases ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; Myopia ; enzymology ; etiology ; Sclera ; enzymology

Objective To investigate the effect of single dose intraosseous injection of simvastatin on tumor vascular structure and function in murine breast cancer. Methods BALB/c mice and 4T1 murine breast cancer cells were used to establish a subcutaneous xenograft model. The mouse model of orthotopic breast cancer received intraosseous injection of a single dose of simvastatin (50 μg) or vehicle only. Frozen tumor tissue sections were prepared for co-immunostained with CD31 andα-SMA. Evans blue dye was injected into the tail vein to observe the vascular permeability. The expression level of HIF-1αwas detected by immunohistochemistry. Results Immunofluorescence dual staining showed that intraosseous injection of simvastatin increased the number of perivascular pericytes in the tumor vessel(P < 0. 05), Evans blue dye content showed that in vivo vessel permeability in the tumor tissue was significantly decreased(P < 0. 05), and the immunohistochemistry results showed that local hypoxic area was significantly improved. Conclusions Single dose intraosseous injection of simvastatin can promote the normalization of tumor vasculature by improving the coverage of pericytes.

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; pathology ; Hepatocytes ; pathology ; Lipopolysaccharides ; Polygonum ; toxicity ; Rats ; Rats, Sprague-Dawley

BACKGROUNDSystemic chemotherapy (SC) is the recommended treatment for gastric cancer with liver metastasis. However, the improvement in survival has been disappointing. The aim of this study was to compare the therapeutic efficacy of gastrectomy with transarterial chemoembolization plus SC (GTC) and SC alone for gastric cancer with synchronous liver metastasis.

METHODSFrom January 2008 to December 2013, 107 gastric cancer patients with synchronous liver metastasis attending the four participating centers were enrolled in this multicenter, ambispective, controlled cohort study. Patients who underwent GTC (n = 32) were compared with controls who were received SC alone (n = 75). The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were response rate to treatment and treatment-related adverse effects.

RESULTSThe median OS was 14.0 months (95% confidence interval [CI ]: 13.1-14.9 months) in the GTC treatment group and 8.0 months (95% CI : 6.6-9.4 months) in SC group, this difference being statistically significant (P < 0.001). The median PFS was significantly longer in the GTC than in the SC group (5 months, 95% CI : 2.2-7.8 months vs. 3 months, 95% CI : 2.3-3.4 months, respectively) (P < 0.001). The rate of response to treatment was significantly better in the GTC than the SC group (59.4% vs. 37.4%, respectively) (P = 0.035). According to multivariate analysis, OS in patients receiving combination treatment was significantly correlated with the size (P = 0.037) and extent of liver metastases (P < 0.001). PFS was also correlated with the extent of liver metastases (P = 0.003).

CONCLUSIONSGTC is more effective than SC alone in patients with gastric cancer with synchronous liver metastasis. GTC therapy prolongs the survival of selected gastric cancer patients with synchronous liver metastasis.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemoembolization, Therapeutic ; methods ; Cohort Studies ; Combined Modality Therapy ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Gastrectomy ; Humans ; Liver Neoplasms ; secondary ; Male ; Middle Aged ; Stomach Neoplasms ; pathology ; therapy

Objective To explore the effect of single local intraosseous injection of small dose simvastatin on the angiogenesis and cardiac function in rats after myocardial infarction. Methods Adult male Wistar rats were divided into sham operation group, myocardial infarction model group and intraosseous injection of simvastatin 0. 5 mg group ( all n=12 per group) . The left anterior descending branch of coronary artery was ligated to establish a rat model of myocardial infarc-tion. The left ventricular function was evaluated by small animal echocardiography at 4 weeks postoperatively. The rest of the rats were sacrificed, the myocardial infarct size was evaluated by TTC staining, and the myocardial neovascularization was detected by immunofluorescence staining. Results We successfully established the rat model of myocardial infarction. The echocardiography showed that the left ventricular systolic function was decreased significantly at 4 weeks after myocardi-al infarction. Intraosseous injection of simvastatin (0. 5 mg) did not improve the left ventricular function after myocardial infarction in the rats. TTC staining showed that intraosseous injection of simvastatin did not reduce myocardial infarct size. Immunofluorescence staining showed that the myocardial capillary density of simvastatin group was slightly higher than that of myocardial infarction model group, but showing no significant difference between them. Conclusions Intraosseous in-jection of simvastatin 0. 5 mg 24 hours after myocardial infarction cannot significantly promote myocardial angiogenesis, which is believed to be beneficial to the revascularization after ischemia, and thus failed to improve the cardiac function.

[Objective]To establish a reliable and accurate preimplantation genetic diagnosis (PGD)method using multiple dis?placement amplification (MDA), which can be applied to the diagnosis of X-linked severe combined immunodeficiency disease (X-SCID).[Methods]Haplotype analysis for the X-SCID family was performedusing five short tandem repeats (STR) markers flanking the both sides of the interleukin-2 (IL-2) receptor gamma chain (IL2RG) gene. MDA technique was used for single-cell whole genomic amplification. The products were used as template in polymerase chain reaction (PCR) of informative STR markers found by linkage analysis for haplotype analysis as well as sequencing of the IL2RG gene exon 5.The amelogenin (AMEL) locus was used to do sex diag?nosis.[Results]Linked analysis revealed 3 STR markers were informative. The method was evaluated with 10 single lymphocytes and 10 single blastomeres. MDA was successful in all single cell. The detection efficiency of gene sequencing of pathogenic IL 2RG exon5 was 100%. The PCR efficiency of 3 STR informative markers and AMEL was 96.3%(77/80)and the average allele drop-out (ADO) rate was 11.5%(7/61). A cycle of PGD was performed on the family, and seven embryos were diagnosed, two of which were normal embry?os. Twin pregnancy occurred after transplantation which were given a healthy baby boy and a healthy baby girl.[Conclusion]In this study, multiple displacement amplification combined with specific amplification/sequencing of pathogenic gene and haplotype analysis in the single cell level of X-linked severe combined immunodeficiency disease were performed. The protocol can avoid misdiagnosis caused by contamination and ADO, and improve the diagnostic efficiency of PGD.

Objective To evaluate the effect on the booster immunization of different dosage of hepatitis B vaccine among children and to provide suggestions for booster immunization.Methods Children aged 5 -1 4 years old were randomly selected who had received the primary immunization of hepatitis B vaccine under 1 year old but had not received the booster immunization in Yuhuan county.A total of 547 children received 5 μg hepatitis A and B combined vaccine boost immunization and 688 children received 1 0 μg hepatitis B vaccine boost immunization in 2009.The anti -HBs levels before and after the boost immunization were detected.Results The anti -HBs positive rates of children received 5 μg and 1 0 μg vaccine boost immunization were 97.81 % and 96.08% respectively and the positive rates in the antibody negative children were 94.78% and 93.62% respectively.While the Geometric Mean Titer (GMT) of anti -HBs were 1 433.1 8 mIU /mL and 21 1 1 .43 mIU /mL respectively,which were both significantly higher than those before the boost immunization (P <0.001 ).The increase of GMT of children received 1 0 μg hepatitis B vaccine was significantly higher than that of children received 5 μg hepatitis A and B combined vaccine (P <0.05).Conclusion Both dosages of hepatitis B vaccine booster immunization are effective for children aged 5 -1 4 years old and 1 0 μg hepatitis B vaccine boost immunization has the better effect.

Objective To observe the concentration of the anti-HBs of children boosted with hepatitis A and B combined vaccine for 3 dosages, and to provide the basis for the implementation of hepatitis B booster immunization. Methods In September 2009 in Yuhuan by employing the cluster sampling method, 123 children, ranging from 6 to 9 years old, who had completed the basic immunization by 0-1-6 procedure without hepatitis B vaccine boosted and without anti-HBs were selected. In the year of 2011 (after 1 year of inoculation) and 2015 (5 years after inoculation), the venous blood samples were collected to determine the concentration of anti-HBs. Results Boosted with hepatitis A and B combined vaccine for 3 times, the anti-HBs of 102 subjects was tested in the next year, of which the anti-HBs of 82 subjects was detected again in the later 5 years. The results suggested that the positive rates of antibody enhanced were 92.16% after 1 year and 78.05% after 5 years, respectively. The average concentration of anti-HBs of these 82 subjects was 2.95 mIU/mL before inoculation, 141.76 mIU/mL one year later and 72.13 mIU/mL 5 years later and there was statistically significant difference among them (P <0.05) . The difference was not statistically significant between subjects with different years of birth (P>0.05) . Moreover, the interaction was existed between the year of blood detection and year of birth (P <0.05) . Conclusion To children aged 6-9 years old whose anti-HBs were negative after the primary immunization of hepatitis B, booster immunization with 3 dosages of hepatitis A and B combined vaccine shows good immune effect against hepatitis B virus.