[Finite element analysis of evaluating the change of the hip joint biomechanics following femoral neck shortening after cannulated screw fixation for osteoporotic femoral neck fracture].

Objective: To evaluate the stress status of femoral head and neck, screws and acetabulum caused by femoral neck shortening after internal fixation of femoral neck fracture with finite element method, and to analyze the stress of proximal femoral neck and acetabulum from the mechanical point of view. Methods: CT scan data of hip of a healthy adult female were collected. Three-dimensional reconstruction MICs and related module function simulation was used to establish the postoperative shortening model of femoral neck fracture with Pauwells angle>50°, which was treated with cannulated screws. The models were divided into four groups: normal femoral neck without shortening, shortening for 2.5 mm, shortening for 7.5 mm and shortening for 12.5 mm. The finite element analysis software MSC. Nastran2012 was used to do the mechanical analysis. The acetabulum surface, femoral head surface, proximal femur and the maximum stress, stress nephogram and other relevant data were collected. Results: The maximum tensile stress and the maximum stress at the fracture site of the femoral neck increased gradually with the increasing of shortening of femoral neck, however, the maximum compressive stress under the femoral neck and the medial cortex decreased gradually; the maximum stress on the surface of the femoral head was 14.9, 15.0, 16.3 and 16.3 MPa, respectively; the maximum stress on the surface of the acetabulum was 10.1, 10.1 and 10.5,11.7 MPa, respectively. Conclusion: The mechanical environment of the hip joint changes with femoral neck shortening. With the increasing of femoral neck shortening, the peak stress of the acetabulum increases continuously. When the femoral neck is shortened seriously, the load distribution is uneven and the complex mobility of hip joint is decreased. In addition, the change of shortening might play a role in the necrosis of femoral head.

CXCR3 mediates chondrocyte injury through regulating nitric oxide.

OBJECTIVE: As a common joint disease, osteoarthritis exhibits increasing trend in recent years. C-X-C motif chemokine receptor 3 (CXCR3) is a kind of chemokine with the characteristic of recruiting inflammatory cells. Its function in osteoarthritis has not been clarified. This study aims to explore the role of CXCR3 in cartilage injury by affecting unfolded protein response (UPR) pathway. PATIENTS AND METHODS: The sample was obtained from osteoarthritis patients to test CXCR3 expression by Real-time polymerase chain reaction (PCR). Chondrocyte apoptosis model was established in vitro induced by interleukin 1ß (IL-1ß) and sodium nitroprusside (SNP). CXCR3 level was downregulated by using siRNA. Cell apoptosis was determined by using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. UPR pathway related factors C/EBP homology protein (CHOP) and glucose regulated protein 78 (GRP78) protein expressions were tested by using Western blot. RESULTS: CXCR3 protein level significantly increased in osteoarthritis patients (2.66 ± 0.25 vs. 1.00 ± 0.05, p<0.05). CXCR3 siRNA significantly reduced nitrate level in chondrocytes induced by IL-ß (35.22 ± 1.76 vs. 17.82 ± 0.89, p<0.05) without affecting cell apoptosis (1.13 ± 0.05 vs. 0.859 ± 0.04, p>0.05). CXCR3 siRNA markedly downregulated nitrate level in chondrocytes (50.63 ± 2.53 vs. 30.63 ± 1.63, p<0.05) and alleviated cell apoptosis induced by SNP (1.98 ± 0.10 vs. 1.25 ± 0.06, p<0.05). UPR pathway C/EBP homology protein (CHOP) and glucose regulated protein 78 (GRP78) participated in the process of chondrocyte apoptosis. CONCLUSIONS: Endoplasmic reticulum (ER) stress signaling pathway CHOP and GRP78 are involved in CXCR3 receptor attenuating chondrocyte apoptosis induced by SNP.

[Study on the enzyme dependant colon targeting prodrug--dexamethasone succinate dextran and its tablets].

AIM: To develop an orally administered colon targeting drug delivery system dexamethasone succinate dextran (DSD) tablets. METHODS: Dexamethasone succinate dextran was synthesized in an anhydrous environment. Using 4-dimethyl aminopyridine and 1,1'-carbonyldiimidazole as the catalyzer. The chemical structure was identified by UV, IR, NMR and MS. The contents of dexamethasone in various samples were determined by HPLC. RESULTS: Dexamethasone was distributed mainly in plasma and gastric contents after the oral administration of common tablets. In contrast, after oral administration of DSD tablets, the recovery of dexamethasone in plasma and gastric contents decreased significantly, while the percentage of dexamethasone in cecum and colon increased obviously. CONCLUSION: The experimental results showed the good colon targeting property of DSD prodrug compared with free dexamethasone.

[Preparation of hepatic targeting antivirus agent NGA-ACV and its targeting property].

Neoglycoalbumin (NGA), a special ligend of asialoglycoprotein receptor on the hepatocyte, was linked via a butanediacyl bridge to acyclovir to form a conjugate NGA-ACV. By using DTA (Differential thermoanalysis) and HPLC analysis, ACV was shown to be connected with NGA by covalent bonds and stable in blood. The radio-biodistribution of 131I-NGA-ACV with high drug density in vivo was carried out in mice. The maximum absorption of 131I-NGA-ACV in liver was 81.7 +/- 10.4% at 5 min. The radioimage of 131I-NGA-ACV with high or low drug density in rabbit showed no significant difference in liver targeting property. The competitive connection tests indicated that 131I-NGA-ACV was concentrated in liver through receptor mediated mechanism. A tentative test of antihepatitis B of NGA-ACV and ACV in vitro showed that the effective dose of the former was significantly lower than that of the latter.

[Study of pharmacokinetics of liver targeting antimalarial agent neoglycoalbumin-primaquine conjugate (NGA-PQ) and primaquine phosphate in mouse].

A normal phase high-performance liquid chromatography process was used to separate and detect primaquine in blood and liver after a single intravenous dose of the hepatic targeting agent neoglycoalbumine-primaquine conjugate (NGA-PQ) and primaquine phosphate (PQP) in mice. 6-Methoxy-8-(4-amino-butyrylamino) quinoline synthesized and identified by us was used as an internal standard to be added to biologic samples obtained from mice at different times after given NGA-PQ or PQP. The mixture was extracted with ether after alkalinization in the PQP group. In the NGA-PQ group, the biological samples must be hydrolized by heating under nitrogen and acid condition in a domestic pressure cooker before extraction. The extracts were evaporated to dryness under nitrogen, then dissolved in the mobile phase (chloroform-methanol-amonium hydroxide = 86.8: 12.5: 0.7). The results showed that the hepatic PQ collecting ratio and the retention time of PQ in liver in the NGA-PQ group were higher and longer than those in the PQP group. The results also point out that NGA-PQ has liver targeting property.

Experimental studies on peripheral nerve regeneration enhanced by nerve growth factor.

The effect of exogenous nerve growth factor (NGF) examined on the neural repair of adult rabbit sciatic nerve was evaluated in the present study. A nerve regeneration chamber was created by suturing the proximal and distal ends of a transected sciatic nerve into a silicone chamber. A gap of 6 mm in chamber was left after removal of a 3 mm piece of nerve in the distal ends and insertion of the proximal and distal stumps into the chamber. Animals were operated on bilaterally, one side of the chamber was filled with a 1 mg/ml NGF/normal saline (NS) (experimental) and the contralateral side with NS (control). The regenerated nerves from within the silicone chamber were dissected and fixed 1 to 5 weeks following surgery for histological studies at both the light microscopic and ultrastructural levels. The NGF chamber showed a more mature regenerated nerve based on a larger diameter of the regenerated nerve trunk, a great number of axons, and thicker myelin sheaths.