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Heterotopic ossification is the formation of pathological bone in non-skeletal tissues (including muscles, tendons or other soft tissues), and the pathogenesis is not completely clear. It is often caused by musculoskeletal trauma, postoperative bone and joint surgery, or damage of the nervous system, the clinical manifestations are joint swelling, pain, and movement disorders, which often occur around the hips, knees, and elbows. At present, the prevention of heterotopic ossification mainly includes drugs, radiotherapy, molecular biological mechanism intervention, and Chinese medicine-related measures. Among them, drugs and radiotherapy are more effective methods to prevent heterotopic ossification. The intervention of molecular biology mechanism to prevent heterotopic ossification has become a new research direction and focus of attention inrecent years, and is basically at the experimental research stage. The treatment of heterotopic ossification includes various methods such as drugs, physical therapy, and surgery. Among them, surgery is recognized as the most effective treatment, however there are still some controversies and disagreements about the choice of operation time and surgical methods.

Osteoarthritis (OA) is a common bone and joint disease with a wild range of risk factors, which is associated with endoplasmic reticulum (ER) stress. The aim of our study was to discuss the possible mechanism of ER stress associated with OA in vivo and explore novel therapeutic method against OA. OA-induced damages in cartilage tissues were evaluated by HE, Safranin O/fast green, and TUNEL staining. The inflammatory factors concentration and the expression of FAP, MMP2, MMP9, Bax, Bcl-2, CHOP, and GRP78 were evaluated by ELISA, real-time PCR, and Western blot analyses. As results, 4-phenylbutyric acid (4-PBA)-treated OA cartilage tissues presented alleviated tissue damage with less apoptotic cells and cytokine production in comparison with advanced-OA tissues. Downregulation of Bax/Bcl-2, CHOP, GRP78, inflammatory factors, and reactive oxygen species generation, and the increase of MMP level detected after 4-PBA treatment indicated an inhibitory effect of 4-PBA on cell apoptosis, inflammatory response, and ER stress in OA. In conclusion, we indicate that ER stress causes cell apoptosis and inflammatory response, resulting in the tissue damage within OA. At the same time, 4-PBA exhibited protective effect on cartilage cells against OA through the inhibition of ER stress.

4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid, which has been demonstrated to regulate endoplasmic reticulum (ER) stress. ER stress-induced cell apoptosis has an important role in skin flap ischemia; however, a pharmacological approach for treating ischemia-induced ER dysfunction has yet to be reported. In the present study, the effects of 4-PBA-induced ER stress inhibition on ischemia-reperfusion injury were investigated in the skin flap of rats, and transcriptional regulation was examined. 4-PBA attenuated ischemia-reperfusion injury and inhibited cell apoptosis in the skin flap. Furthermore, 4-PBA reversed the increased expression levels of two ER stress markers: CCAAT/enhancer-binding protein-homologous protein and glucose-regulated protein 78. These results suggested that 4-PBA was able to protect rat skin flaps against ischemia-reperfusion injury and apoptosis by inhibiting ER stress marker expression and ER stress-mediated apoptosis. The beneficial effects of 4-PBA may prove useful in the treatment of skin flap ischemia-reperfusion injury.

To explore surgical methods and clinical effects of three different types of mini skin flap transplantation for repairing finger soft tissue with bone defect.Thirty-three patients with finger soft tissue or bone defect were treated from December 2014 to October 2016, including 24 males and 9 females aged from 21 to 52 years old with an average of (36.42±5.70) years old, and soft tissue defect area ranged from 1.3 cm×1.8 cm to 2.3 cm×4.2 cm. According to damage degree, nature and patients' options, 15 finger of 15 cases were adopted retrograde dorsal metacarpal artery perforators fascia flap, 10 fingers of 9 cases were treated with free foot artery descending branch wrist skin flap, 9 fingers of 9 cases were treated with free the second toe details phalanges compound flap. Survival rate, postoperative complications and finger function assessed by Dargan functional criteria at the latest follow up were observed.All flaps were survived, both of donor site and recipient site were without deep infected. The donor site of one patient occurred necrotic, and the distal donor site of one patient occurred surface necrotic, then healed by active dressing change. All patients were followed up from 6 to 16 months with an average of(8.34±1.28) months. Two points of finger recognition were restored between 8 and 12 mm with an average of (8.84±0.43) mm, and the appearance, texture and sensory functions of skin flap were restored. No obvious complications were observed on the donor site. According to Dargan function evaluation of finger joints, 18 patients got excellent results, 14 moderate and 1 good.Three kinds of mini skin flap could receive good results in repairing soft tissue of finger or bone defect. Reverse dorsal metacarpal artery perforator fascia flap is not necessary with anastomosing blood vessels and has advantages of safe, simple and high survival rate. Descending branch of superior cutaneous branch of free ulnar artery could cut multiple other perforator flaps simultaneously, and the scar is small and hidden. Dissociated the second toe combined metatarsal phalangeal flap could repair shape and function of finger to the maximum extent and donor site is hidden.

The aim of the present study was to investigate the effect of glucocorticoids in osteoblasts and to examine the role of β‑ecdysterone in the pathogenesis of glucocorticoid‑induced osteoporosis. Osteoblasts were induced from bone marrow mesenchymal stem cells, which were isolated from C57BL/6 mice. Cell viability and apoptosis of osteoblasts were measured by Cell Counting Kit‑8 and flow cytometry analysis, respectively. The expression of related genes and proteins was measured by reverse transcription quantitative polymerase chain reaction and western blot analysis respectively. Dose‑dependent decreases in the cell proliferation and differentiation were observed in dexamethasone (Dex)‑treated osteoblasts, evidenced by downregulation in the activity of alkaline phosphatasedecreased expression levels of Runt‑related transcription factor 2 and osteocalcin, and upregulated expression of RANK ligand. Dex also induced apoptosis and inhibited autophagy of osteoblasts, evidenced by upregulated B‑cell lymphoma 2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio and the activation of mammalian target of rapamycin (mTOR), and decreased expression levels of Beclin‑1, autophagy protein 5 and microtubule‑associated protein 1 light chain 3 II. The effects on cell proliferation, apoptosis and autophagy induced by Dex were reversed by β‑ecdysterone in a dose‑dependent manner. Therefore, β‑ecdysterone may be a promising candidate drug for the treatment of osteoporosis through inducing osteoblast autophagic activity by inactivating mTOR.

Osteoarthritis (OA) is a common bone and joint disease with a wild range of risk factors, which is associated with endoplasmic reticulum (ER) stress. The aim of our study was to discuss the possible mechanism of ER stress associated with OA in vivo and explore novel therapeutic method against OA. OA-induced damages in cartilage tissues were evaluated by HE, Safranin O/fast green, and TUNEL staining. The inflammatory factors concentration and the expression of FAP, MMP2, MMP9, Bax, Bcl-2, CHOP, and GRP78 were evaluated by ELISA, real-time PCR, and Western blot analyses. As results, 4-phenylbutyric acid (4-PBA)-treated OA cartilage tissues presented alleviated tissue damage with less apoptotic cells and cytokine production in comparison with advanced-OA tissues. Downregulation of Bax/Bcl-2, CHOP, GRP78, inflammatory factors, and reactive oxygen species generation, and the increase of MMP level detected after 4-PBA treatment indicated an inhibitory effect of 4-PBA on cell apoptosis, inflammatory response, and ER stress in OA. In conclusion, we indicate that ER stress causes cell apoptosis and inflammatory response, resulting in the tissue damage within OA. At the same time, 4-PBA exhibited protective effect on cartilage cells against OA through the inhibition of ER stress.

Osteoporosis is an aging process of skeletal tissues with characteristics of reductions in bone mass and microarchitectural deterioration of bone tissue. The present study aimed to investigate the effects of glucocorticoid‑induced osteoporosis on osteoblasts and to examine the roles of β‑ecdysterone (β‑Ecd) involved. In the present study, an in vivo model of osteoporosis was established through the subcutaneous implantation of prednisolone (PRED) into Sprague‑Dawley rats, with or without a subcutaneous injection of β‑Ecd (5 or 10 mg/kg body weight). Expression of Beclin‑1 and microtubule‑associated protein 1A/1B‑light chain 3I/II and apoptosis in lumbar vertebrae tissues was measured by immunofluorescence and TUNEL assays, respectively. Serum concentration of calcium and phosphorus, and the activity of tartrate‑resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were measured by biochemical assay. Reverse transcription‑quantitative polymerase chain reaction and western blotting was used for detect the expression of related genes and proteins. PRED treatment inhibited bone formation by decreasing bone mineral density, and suppressing the expression of Runt‑related transcription factor 2 and bone morphogenetic protein 2, while enhancing the activity of alkaline phosphatase, upregulating the expression of receptor activator of nuclear factor-κB ligand, and increasing the serum content of calcium, phosphorus and tartrate‑resistant acid phosphatase in rats. Additionally, PRED was revealed to inhibit autophagy through the downregulation of Beclin‑1, autophagy protein 5 and microtubule‑associated protein 1A/1B‑light chain 3I/II expression, whereas it induced the apoptosis, through the activation of caspase‑3 and the suppression of apoptosis regulator BCL2 expression. Notably, the PRED‑induced alterations in bone formation, autophagy and apoptosis were revealed to be attenuated by β‑Ecd administration. In conclusion, the findings of the present study suggested that β‑Ecd may be a promising candidate for the development of therapeutic strategies for the treatment of osteoporosis, through the induction of autophagy and the inhibition of apoptosis in vivo.

To explore individual choice and therapeutic effect of distal fibula internal fixation in treating ankle fractures in elderly.From May 2012 to April 2015, 68 elderly patients with ankle fractures were treated by surgical operation, included 37 males and 31 females with an average of 69.2 years old ranging from 62 to 81 years. According to Danis-Weber classification, there were 19 cases belong to type A, 31 cases belong to type B, and 18 cases belong to type C. According to Lange-Hanson classification, 22 cases were supinatio-extorsion, 18 were pronate-extorsion, 19 were supinatio-adduction, and 9 were pronate-abduction. All patients were performed individyually with different internal fixation methods for the treatment of distal fibula fracture according to different types of fracture. Clinical results were evaluated based on clinical examination, radiographic evaluation and AOFAS score.Twelve patients were treated with Herbert screw, 7 cases with Kirschner wire tension band, 5 cases with 1/3 tube plate, 6 cases with reconstruction plate, 17 cases with fibular end dissection steel plate composite, and 21 cases with distal fibula anatomic locking plate. All patients were followed up from 12 to 26 months with an average of 17.7 months. The operative incision of all patients were primary healed. And there was no bone nonunion, ankle instability, internal fixation loosening and fracture occurred. Fracture healing time ranged from 2.7 to 4 months with an average of 3.2 months, and had significant differences among different groups(Good clinical results could be obtained by using individualized internal fixation for distal fibula fracture for the treatment of the ankle fractures in elderly.

To discuss the surgical method and clinical efficacy for open tarsometatarsal joint injuries.From March 2011 to January 2015, 21 patients with open tarsometatarsal joint injuries were treated with stage-surgery method, including 14 males and 7 females with an average age of 45.6 years old ranging from 20 to 75 years. Injury site occurred in the left foot of 13 cases and right foot of 8 cases. Traffic injury was in 5 cases, crush injury in 6 cases, heavy crushing was in 10 cases. According to Myerson to classify for tarsometatarsal joint injury, 5 cases were type B2, 9 cases were type C1, and 7 cases were type C2. And according to Gustilo to typing for soft tissue injury, 5 cases were type IIB, 10 cases were type IIIA, 6 cases were type IIIB. Fracture healingand complications were observed after operation and clinical effects were evaluated according to the midfoot score of AOFAS.All the patients were followed up from 11 to 40 months with an average of 16.2 months. The fracture healing time was from 10 to 16 weeks with an average of 12.3 weeks. No complications such as deep infection, nonunion and osteomyelitis were found. Midfoot score of AOFAS at last follow-up was 83.0±14.9, 9 cases got excellent results, 8 good, 2 fair, 2 poor. Two patients complicated with severe traumatic arthritis once again underwent tarsometatarsal arthrodesis.For the treatment of open tarsometatarsal joint injury, reasonable debridement, comprehensive assessment for the soft tissue injury, correctly grasp the surgical indications and time of internal fixation, can reduce the incidence of deep infection and osteomyelitis.

Monotropein, the primary iridoid glycoside isolated from Morindacitrifolia, has been previously reported to possess potent antioxidant and antiosteoporotic properties. However, there is no direct evidence correlating the antiosteoporotic effect of monotropein with its observed antioxidant capacity, and the molecular mechanisms involved in mediating these processes remain unclear. Therefore, the aim of the present study was to investigate the protective effects of monotropein against oxidative stress in osteoblasts and the mechanisms involved in mediating this process. Osteoblast viability was evaluated using the MTT assay. The mitochondrial membrane potential and reactive oxygen species were detected by flow cytometry analyses. Western blotting and enzyme‑linked immunosorbent assays were performed to detect protein expression levels. A significant reduction in osteoblast viability was observed at 24 h following exposure to various concentrations (100‑1,000 µM) of H2O2 compared with untreated osteoblasts. The cytotoxic effect of H2O2 was notably reversed when osteoblasts were pretreated with 1‑10 µg/ml monotropein. Pretreatment with 1-10 µg/ml monotropein increased the mitochondrial membrane potential and reduced the generation of reactive oxygen species in osteoblasts following exposure to H2O2. In addition, the H2O2‑induced increase in apoptotic markers (caspase-3 and caspase-9) and H2O2-induced reduction in sirtuin 1 levels were significantly reversed following pretreatment of cells with monotropein. Furthermore, monotropein significantly reduced H2O2‑induced stimulation of NF‑κB expression, in addition to the expression of a number of proinflammatory mediators. These results indicate that monotropein suppresses apoptosis and the inflammatory response in H2O2‑induced osteoblasts through the activation of the mitochondrial apoptotic signaling pathway and inhibition of the NF‑κB signaling pathway.

To investigate the methods and clinical effects of repairing finger soft tissue defect with free vascularized flaps based on the wrist cutaneous branch of ulnar artery.From February 2010 to December 2012, 16 patients with finger soft tissue defects were repaired by free vascularized flaps based on the wrist cutaneous branch of ulnar artery, including 10 males and 6 females with an average age of 38.2 years old ranging from 18 to 52 years. Among them, 5 cases caused by hot crush injury, 8 cases caused by machine crush injury, 3 cases caused by firecracker burst injury. The defect area varied from 1.3 cm x 2.3 cm to 2.6 cm x 5.0 cm. The flap area varied from 1.5 cm x 2.5 cm to 2.8 cm x 5.2 cm. The appearance and two-point discrimination of flap were observed after operation.All flaps survived and wounds healed primarily. No wound infection and skin necrosis were found in donor site and recipient site. Among repair methods, direct suture in forearm donor site had 11 cases and skin graft had 5 cases. All patients were followed up from 6 to 24 months with an average of 10.8 months. The appearance of flap was not fat or clumsy, texture and color were similar to the recipient site, the sensation were good, two-point discrimination was 6 to 9 mm. The appearance of donor site were well complicated with mild scarring without dysfunction obviously.The free vascularized flaps based on the wrist cutaneous branch of ulnar artery has the advantages of vascular anatomy constant,thickness moderate and carry sensory nerves, etc, which is effective way to repair finger soft tissue defects.

To discuss the effect of surgical staging and using craft bone with vancomycin for the treatment of calcaneal fractures.From January 2006 to December 2012,13 patients with open calcaneal fractures were treated including 9 males and 4 females with an average of 35.2 years old ranging from 23 to 66. All cases were emergency cases. According to Sanders classification of calcaneal fractures, 2 cases were type II, 7 cases were type III, 4 cases were type IV. According to Gustilo-Anderson soft tissue injury classification, 8 cases were type II, 2 cases were type III A, 2 cases were type III B, 1 case were type III C. Firstly a thorough debridement or VSD procedures were applied,secondly calcaneal fracture were treated with open reduction, plate fixation and bone graft complex with antibiotics. Based on clinical examination, radiographic evaluation, and American Foot and Ankle Surgery Society (AOFAS), ankle function were evaluated after operation.Open wounds were headed after dressing and repairing,, lateral calcaneal wound were healed during the first period. All patients were followed up for 6 to 36 months (means 14.5 months). Fracture healing time was 14 to 20 weeks (means 16.2 weeks). Last follow-up AOFAS ankle-hindfoot score was (80.0 +/- 7.4) ranging from 55 to 95.For patients with open fractures, through reasonable clinical evaluation, staging operation, using bone graft with antibiotics can reduce the incidence of postoperative wound infection and promote fracture healing.

To investigate the effcacy of the staple fixation for the treatment of hamate metacarpal joint injury.From May 2009 to November 2012,16 patients with hamate metacarpal joint injury were treated with staple fixation including 10 males and 6 females with an average age of 33.6 years old ranging from 21 to 57 years. Among them, 11 cases were on the fourth or fifth metacarpal base dislocation without fractures, 5 cases were the fourth or fifth metacarpal base dislocation with avulsion fractures of the back of hamatum. Regular X-ray review was used to observe the fracture healing, joint replacement and position of staple fixation. The function of carpometacarpal joint and metacarpophalangeal joint were evaluated according to ASIA (TAM) system evaluation method.All incision were healed well with no infection. All patients were followed up from 16 to 24 months with an average of (10.0 +/- 2.7) months. No dislocation recurred, the position of internal fixator was good,no broken nail and screw withdrawal were occurred. Five patients with avulsion fracture of the back of hamatum achieved bone healing. The function of carpometacarpal joint and metacarpophalangeal was excellent in 10 cases,good in 5 cases, moderate in 1 case.The application of the staple for the treatment of hamatometacarpal joint injury has the advantages of simple operation, small trauma, reliable fixation, early postoperative function exercise and other advantages, which is the ideal operation mode for hamatometacarpal joint injury.

Controversy exists concerning the need for operative repair of the deltoid ligament during management of acute ankle fractures. The purpose of our report was to identify the indications for surgical intervention for deltoid ligament injury in the setting of ankle fractures. Furthermore, we aimed to elucidate the clinical outcomes after deltoid ligament repair in this setting. This was a multicenter study, involving 4 clinical institutions. From January 2006 to December 2011, 1533 ankle fractures underwent surgical intervention. Of this group, 131 deltoid ligament ruptures (8.55%) were identified and repaired operatively. Of the 131 patients, 74 were male (56.5%) and 57 were female (43.5%), with a mean age of 33.2 (range 16 to 63) years. The outcome measures included the clinical examination findings, radiographic findings, American Orthopaedic Foot and Ankle Society ankle-hindfoot scores, visual analog scale (VAS) scores, and Medical Outcomes Study Short Form 36-item questionnaire scores. All incisions healed primarily. A total of 106 patients were followed up for a minimum of 12 (range 12 to 72) months, with an average follow-up period of 27 months. The mean interval to fracture union was 14.5 (range 9 to 16) weeks. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score at the latest follow-up visit was 91.4 (range 83 to 100) points. The mean visual analog scale score was 1.2 (range 0 to 6) points. The mean Short Form-36 score was 91.2 (range 80 to 96) points. Compared with the preoperative scores, all the 3 outcome measures had improved significantly postoperatively (p < .05). The postoperative stress radiographs did not reveal any ankle instability. None had evidence of post-traumatic arthritis of the ankle from the clinical examination and radiographs. A reasonable clinical evaluation and surgical repair was executed, with an appropriate repair technique chosen according to the site of deltoid ligament rupture. The results of the present multicenter study have shown that deltoid ligament rupture can be repaired in patients with an unstable medial ankle after fracture fixation and prevent ankle stabilization-related complications.