Effects of hypoxia environment on osteonecrosis of the femoral head in Sprague-Dawley rats.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a disease in which the blood supply of the femoral head is interrupted or damaged, resulting in joint dysfunction. Hypoxic environments increase the expression of EPO, VEGF, and HIF causes vascular proliferation and increases the blood supply. It also causes the organism to be in a state of hypercoagulability and increases thrombosis. Therefore, the purpose of this study was to explore the occurrence of ONFH after the use of glucocorticoids (GCs) under conditions of hypoxia tolerance for a long time. MATERIALS AND METHODS: Sprague-Dawley rats were fed in a hypobaric hypoxic chamber at an altitude of 4000 m, the whole blood viscosity, and plasma viscosity were determined to analyze the blood flow and hemagglutination. Western blotting, polymerase chain reaction, and immunohistochemistry were used to detect EPO, VEGF, CD31, and osteogenesis related proteins. Femoral head angiography was used to examine the local blood supply and micro-CT scanning was used to detect the structure of the bone trabecula. RESULTS: Under hypoxic environments, the expression of EPO and VEGF increased, which increased the local blood supply of the femoral head, but due to more severe thrombosis, the local blood supply of the femoral head decreased. CONCLUSIONS: Hypoxic environments can aggravate ONFH in SD rats; this aggravation may be related to the hypercoagulable state of the blood. We suggest that long-term hypoxia should be regarded as one of the risk factors of ONFH and we need to conduct a more extensive epidemiological investigation on the occurrence of ONFH in hypoxic populations.

CXCR4 blockade sensitizes osteosarcoma to doxorubicin by inducing autophagic cell death via PI3K­Akt­mTOR pathway inhibition.

Doxorubicin is one of the most frequently used chemotherapy drugs in the treatment of osteosarcoma (OS), but the emergence of chemoresistance often leads to treatment failure. C­X­C motif chemokine receptor 4 (CXCR4) has been demonstrated to regulate OS progression and metastasis. However, whether CXCR4 is also involved in OS chemoresistance and its molecular mechanisms has yet to be fully elucidated. In the present study, CXCR4­mediated autophagy for OS chemotherapy was investigated by western blot analysis, transmission electron microscopy and confocal microscopy. CXCR4 silencing enhanced doxorubicin­induced apoptosis by reducing P­glycoprotein in CXCR4+ LM8 cells, while CXCR4 overexpression promoted OS doxorubicin resistance in CXCR4­ Dunn cells. Furthermore, CXCR4 silencing with or without doxorubicin increased the expression of beclin 1 and light chain 3B, and the number of autophagosomes and autolysosomes, as well as induced autophagic flux activation by suppressing the PI3K/AKT/mTOR signaling pathway. In addition, pretreatment with the autophagy inhibitor bafilomycin A1 attenuated CXCR4 abrogation­induced cell death. Finally, the CXCR4 antagonist AMD3100 synergistically reinforced the antitumor effect of doxorubicin in an orthotopic OS mouse model. Taken together, the present study revealed that CXCR4 inhibition sensitizes OS to doxorubicin by inducing autophagic cell death. Therefore, targeting the CXCR4/autophagy axis may be a promising therapeutic strategy to overcome OS chemotherapy resistance.

Protosappanin a inhibits osteoclastogenesis via reducing oxidative stress in RAW264.7 cells.

Protosappanin A (PrA), obtained from the traditional Chinese herbal medicine, Caesalpinia sappan L. (Lignum Sappan), possesses a lot of pharmaceutical activities. Typically, it is a potent antioxidant. This study makes an effort to test its protective effects against osteoporosis by partially reducing oxidative stress in RAW264.7 cells and a mouse ovariectomized (OVX) osteoporosis model. The influence that PrA affected on osteoclastic proliferation and differentiation under oxidative status was investigated. Our results revealed that PrA significantly inhibited the proliferation of RAW264.7 cells in oxidative stress conditions. Moreover, it suppressed some osteoclastic markers by TRAP staining, bone section assay and quantitative real-time PCR. PrA decreased reactive oxygen species (ROS) generation in RAW264.7 cells. In vivo, our results demonstrated that PrA supplementation improved some serum oxidative markers, including malondialdehyde (MDA) and reduced glutathione (GSH), and inhibited some osteoclastic markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones by micro-CT assay. In summary, these findings showed that protection by PrA against osteoporosis is associated with a reduction in oxidative stress, suggesting that PrA may be useful in bone resorption related diseases, especially osteoporosis.

[Surgical treatment strategy for flatfoot related with accessory navicular].

Accessory navicular source flatfoot is one of the foot deformity of clinical common disease,its treatment method is more controversial, differences in clinical efficacy of different surgical methods, according to accessory navicular source flatfoot symptoms of surgical treatment,there is no uniform standard, around a pair of accessory navicular excision how to reconstruct the arch produced a series of operation methods, the clinical curative effect of different operative methods produce also different, how to develop the operation strategy, choose operation method, and after acessory navicular excision whether to rebuild posterior tibial tendon, how to rebuild, the problems such as how to rebuild is the research hotspot and difficulty, looking forward to further research.

[Application of the tension skin flap with different shapes in the pedicle of the reverse neurocutaneous island flap].

OBJECTIVE: To investigate the effects of the tension skin flap with different shapes on the transplantation of the reverse neurocutaneous island flap. METHODS: From January 2006 to January 2012,there were 21 patients in the study (including 15 males and 6 females), and aged from 14 to 58 years old (35 years old on average). Tension skin flaps with different shapes (triangle ,round and ellipse) were used to improve the blood supply of the reverse neurocutaneous island flap. The tension skin flaps in the pedicle were designed triangularly (10 patients), spherically (8 patients) or elliptically (3 patients). There were 5 patients with defects in the hand (the size from 5.0 cm x 2.0 cm to 8.0 cm x 5.0 cm), and 16 patients with defects in the foot and inferior segment of leg, or around the ankle (the size from 6.0 cm x 4.0 cm to 13.0 cm x 7.0 cm). And all the patients were with the tendon and bone exposed. All the flaps were reversal transplanted, including 5 dorsal neurocutaneous flaps of foot, 4 superficial peroneal neurocutaneous flaps, 4 saphenous neurocutaneous flaps, 3 sural neurocutaneous flaps, 2 superficial radial neurocutaneous flaps, 3 lateral neurocutaneous flaps of forearm. And the survival rate, appearance and sensory recovery of the flaps were analyzed. RESULTS: The distant part of the reversed sural neurocutaneous island flap in 1 case necrosized and healed after dressing change. The other flaps survived entirely, and the donor site all healed primarily. The follow-up time was from 3 months to 2 years (averaged 7 months), and all the flaps had recovered pain and warm sensation with perfect appearance. CONCLUSION: The tension skin flap in the pedicle can enhance the blood supply and promote survival rate of the reverse neurocutaneous island flap, and can also improve its appearance.

[Clinical effect analysis of total knee replacement for treating gonarthrosis with severe deformities].

OBJECTIVE: To investigate the prosthesis selection, precaution and curative effect of total knee replacement in severe gonarthrosis. METHODS: From January 1996 to July 2009, 50 patients (58 knees) with severe gonarthrosis underwent total knee replacement, included 12 males and 38 females, aged from 46 to 80 years with an average age of 66.5 years old. Six artificial hinged knee joints, 37 general knee joints and 15 ScorpioNRG knee joints were used according to the deformity of the knees. Fifty patients (58 knees) were followed up and evaluated with the HSS (the Hospital for Special Surgery Knee Score) scoring system. RESULTS: The duration of follow-up ranged from 6 months to 8 years (means 62 months). According to the HSS scoring system, the mean preoperative score was (38.6 +/- 8.76) points, and the postoperative score was (86.50 +/- 9.45) points. The clinical effect was excellent in 20 cases (23 knees), good in 28 cases (32 knees),and acceptable in 2 cases (3 knees). CONCLUSION: Stable and functional recovery knee joint without deformities and pains could be obtained after total knee replacement by carefully chosing of prosthetic replacements according to the different degrees of joint deformity of severe gonarthrosis.