OBJECTIVE To evaluate the long-term toxicity of fully human anti-human tumor necrosis factor-α monoclonal antibody(anti-hTNF-α FHMA)for injection in cynomolgus monkeys. METHODS Forty cynomolgus monkeys were randomly divided into 5 groups (4 males and 4 females in each group):negative control group,adalimumab 10 mg·kg-1 group,anti-hTNF-αFHMA 2,10 and 50 mg·kg-1 groups. Cynomolgus monkeys in each group were injected sc once a week for 5 consecutive times, followed by 4 weeks of recovery. During the test,general clinical observation,body mass,body temperature,electrocardiogram(ECG),hematology,coagulation function,blood biochemistry,urine, ophthalmology,immune index,and pathological changes in organs and tissues were observed. At the same time,plasma drug concentrations were detected and the toxicokinetics parameters were analyzed. RESULTS No significant toxicological changes related to drugs were observed in general clinical observation,body mass,body temperature,ECG,ophthalmic examination,blood cell counts,coagu?lation function,blood biochemistry,urine analysis,lymphocyte subsets,cytokines,serum immuno?globulin,serum complement. Neutralizing anti-drug antibody(ADA)could be detected in adalimumab group and anti-hTNF-αFHMA groups. Anti-hTNF-αFHMA showed linear dynamic characteristics in cyno?molgus monkeys. At the same dose(10 mg·kg-1),anti-hTNF-αFHMA had similar immunogenicity and kinetics characteristics to adalimumab. CONCLUSION The level of anti-hTNF-α FHMA at which no adverse effect was observed was 50 mg · kg-1,which is equivalent to 75 times clinical dosage of quasi (0.67 mg·kg-1),which suggests that anti-hTNF-αFHMA be safe in clinical use.

Objective:To introduce a novel surgical technique for dissecting perforator vessels (orderly retrograde four-side dissection) in anterolateral thigh perforator flap (ALTPF) and explore its clinical outcome.Methods:Respective analysis of 94 patients who underwent reconstruction of soft tissue defects with ALTPF which were dissected by orderly retrograde four-side dissection between June, 2013 and December, 2016. After surgery, the survival of flaps, recovery in shape and function of the recipient sites, and the effect on shape and function of the donor sites were observed.Results:The size of ALTPF ranged from 7 cm×5 cm to 32 cm×10 cm. Ninety-four perforators were included in 94 ALTPF, which were 89 perforators of the descending branch of circumflex femoral lateral artery, 4 perforators of the transverse branch of circumflex femoral lateral artery and 1 perforator of femoral medial artery. The time for flap harvesting was 35-95(54.39±16.39) min. Success rate of perforator harvesting was 98.9%, only 1 perforator was injured and another encountered vasospasm during surgery. Three cases had vascular crisis after flap transfer with 2 venous crises and 1 artery crisis. All of the flaps completely survived except 1 that had a partial necrosis. The follow-up time was (12.91±9.17) months. No muscular weakness on donor sites was shown in all cases.Conclusion:Orderly retrograde four-side dissection of perforator vessels in the ALTPF has achieved less donor site morbidity, shorter surgical time and is safer than the traditional techniques. It is a reliable technique to harvest perforator flaps.

A child who suffered a complex and exceptionally large soft tissue defects of both lower extremities and feet was referred in January, 2017. A debulking deep inferior epigastric perforator (DIEPF) was used to cover the defect in right shank. The defects in left shank and foot were reconstructed by latissimus dorsi flap and bilateral debulking anterolateral thigh perforator flap (ALTPF) . Two years after operation, the appearance and texture of both lower limbs were good, and the child could walk and run almost normally. There were slightly noticeable scars left in both thighs and the back.

Objective To investigate the feasibility and clinical effects of chimeric perforator flap based on the descending branch of lateral circumflex femoral artery (d-LCFA) for reconstructing the three-dimensional tissue defect in lower extremities. Methods From May, 2008 to June, 2017, 79 cases of soft tissue defects with dead space were repaired by using a d-LCFA chimeric perforator flap, in which 33 cases of car accident trauma, 12 cases of chronic tibial osteomyelitis, 10 cases of plowing machine injury, 9 cases of chronic calcaneal osteomyelitis, 6 cases of falling injury, 5 cases of crushing injury, 3 cases of spoke injury, and 1 case of suppurative knee arthritis. These patients were accompany with different degrees of infection and dead space after radical debridement. The dead cavity was filled by muscular flap, and perforator flap covered the superficial wound. Recording the flap 's appearance, color, texture, osteomyelitis recurrence and the patient 's knee extension at 1, 3, 6, 9 and 12 months followed-up. Results Seventy-five flaps survived without complications, and the donor sites were closed directly. All patients had no post-operative hematoma or secondary infection. Vascular crisis occurred in 2 days after the operation in 4 flaps, 1 flap had an arterial crisis on the second-postoperative-day, and the flap was necrotic after surgical exploration. The deep cir-cumflex iliac artery chimeric perforator flap was used for repairing. Three flaps with venous crisis during 48 h after operation, in which 2 flaps survived eventually after surgical exploration, and another flap was necrosis and repaired by skin graft. The followed-up periods ranged from 3 months to 30 months (mean, 9.7 months). All flaps had satisfied with appearance and texture. There were no osteomyelitis recurrence and any ranges of motion limitations in the hip and knee joints of the operated leg. Conclusion The chimeric perforator flap with d-LCFA merely anastomosed 1 group vascular pedicle can make the dead space be filled and cover the superficial wound simultaneously. It is an ideal option for reconstructing the skin defect with dead space in lower extremity, which can improve the quality of restoration of recipient site and reduce the damage of donor site.

Objective:To explore the curative effects of thoracodorsal artery chimeric perforator flap used to repair extremity soft tissue defects complicated with a deep dead cavity.Methods:From July 2014 to July 2019, 17 patients with extremity soft tissue defects complicated with a deep dead cavity were repaired by a thoracodorsal artery chimeric perforator flap at Department of Orthopaedics, Xiangya Hospital. They were 10 males and 7 females, aged from 2 to 39 years (mean, 20.2 years). There were 7 cases of traffic accident trauma, 5 ones of chronic osteomyelitis, 2 ones of crushing injury and 3 ones of radical resection of tumor. The defects were located at the lower extremity in 15 cases and at the upper extremity in 2. The wound sizes ranged from 5 cm × 3 cm to 24 cm × 9 cm. All the wounds were complicated somewhat with a dead cavity or exposure of deep tissues after debridement. The muscular component of thoracodorsal artery chimeric perforator flap was used to fill the dead cavity while the skin component to cover the superficial wounds. The flap donor sites were closed directly. The flap survival and donor site recovery were followed up regularly after operation. The curative effects were assessed according to the comprehensive evaluation criteria of hand surgery for flaps.Results:Necrosis of the distal flap occurred in only one case which responded to dressing change; the flaps survived uneventfully in the other 16 cases. The recipient and donor sites of flaps healed primarily in all patients. Venous crisis developed in one case which survived uneventfully after vascular crisis exploration. The 17 patients were followed up for 6 to 24 months (mean, 15.8 months). In all patients the flap presented with good color, texture and elasticity but without obvious swelling. At the last follow-up, the curative effects by the comprehensive evaluation criteria of hand surgery for flaps were excellent in 10 cases, good in 6 and fair in one. Only linear scar remained at the flap donor site and abduction of the shoulder was not affected.Conclusion:The thoracodorsal artery chimeric perforator flap is an ideal means for repair of extremity soft tissue defects complicated with a deep dead cavity because it can repair the deep dead cavity and body surface wounds at the same time only after anastomosis of a bundle of vascular pedicles.

Objective:To investigate the feasibility and clinical effects of the chimeric multi-paddled anteriolateral thigh perforator flap (ALTP) for reconstruction of complex defects in extremities, which was pedicled with the descending branch of lateral circumflex femoral artery (d-LCFA).Methods:From August, 2010 to December, 2017, 11 cases of severe soft-tissue defects were repaired with this flap, including 4 cases of car accident trauma, 2 of machine injury, 2 of fall injuries, 1 of ploughing machine injury, 1 of crushing injury, and 1 of spoke injury. The injuries accompanied with different degrees of infections, dead space and left huge soft-tissue defects after radical debridement (10.0 cm×9.0 cm-20.0 cm×18.0 cm) . Dead cavity was filled by the muscular flap, and the large area soft-tissue defects were repaired by chimeric multi-paddled perforator flap. Appearance, colour and texture of the flap, recurrence of infection and knee extension were recorded at 1, 3, 6, 9 and 12 months follow-up.Results:After the operation, all recipient sites had no hematoma and no infection. Eight flaps survived successfully, and donor sites healed primarily. One flap had partial necrosis because of a mechanical stretch of the perforator during the operation, then repaired by the ipsilateral chimeric perforator flap based on d-LCFA. One flap occurred vascular crisis on the second day after the surgery, and it was rescued and survived completely after surgical exploration. The other flap which repaired wound on hand had partial necrosis too, and then repaired with posterior interosseous artery perforator flap. The follow-up periods ranged from 2 to 32 (mean, 10.2) months. All flaps had satisfactory appearance and texture. Only linear scars left at the donor sites. There were no motion limitations at the hip and knee joints of the effected leg.Conclusion:The anteriolateral thigh perforator flap combined with multi-paddled and chimeric techniques can reduce donor site morbidities, simplify the anastomosis of blood vessel, and improve the appearance and effects of the recipient site. It is a feasible method in repairing severe soft tissue defects of limbs.

Objective: To explore the clinic effects of posterior tibial artery perforator pedicled propeller flaps for children heel injuries in spoke wheel accidents. Methods: During August 2010 and May 2016, 12 children with spoke heel injuries were covered by posterior tibial artery perforator pedicled propeller flaps. The skin and soft tissue defects ranged from 4 cm×3 cm to 8 cm×3 cm. There were 4 cases with achilles tendon exposure, 8 cases with achilles tendon defect in distal, 6 cases with part of calcaneus defect. The range of achilles tendon defect were 2-5 cm(average 3.2 cm). The flap size ranged from 8.0 cm×3.0 cm to 12.5 cm×4.0 cm. In 6 cases, fascia tissue was harvested to fill the heel cavity. The donor sites were closed directly in 11 cases, and covered with skin grafting in one case. Results: All flaps survived smoothly with no complications. All patients were followed up 3 months to 20 months (mean, 8.5 months). The color and appearance of the flaps were satisfactory, with no impact on wearing shoes and walking. Conclusions Posterior tibial artery perforator pedicled propeller flap which has reliable blood supply, less donor-site morbidities, cosmetic shape, simple operation and less postoperative complications is an ideal method for surfacing heel spoke injuries in children.

Objective: To explore the feasibility of free circumflex scapular artery perforator flap for repairing the wounds of the limbs in children. Methods: From April, 2010 to October, 2017. 39 cases of pediatric patients who suffered from skin and soft defects in the limbs with exposure of bone, joint or tendon were repaired by the circumflex scapular artery perforator flap.The flap size ranged from 6.0 cm×3.5 cm to 16 cm×14 cm. Doppler detection was used to determine the distribution of the descending, ascending and transverse branches of the circumflex scapular artery. The proper perforator flap type was selected according to the shape and the size of the wound. Results: Thirty-seven flaps survived smoothly. Venous crisis occurred in one case and arterial crisis occurred in another case at the second postoperative day. Both flaps survived completely after exploration. All flaps were healed at the recipient sites. Delayed healing of the donor site wound occurred in two cases. All cases were followed up for 3 to 36 months (average 12 months), and the appearance and function of the recipient sites were satisfactory. Only linear scars remained in the donor sites. Conclusions The free circumflex scapular artery perforator flap is an ideal method to resurface the soft-tissue defects of extremities in children.

Objective: To explore the feasibility and efficiency of deep inferior epigastric perforator flap (DIEP) based on individual design which was used for reconstructing the various types of soft tissue defects in extremities. Methods: From September 2009 to October 2017, ninety three patients were included for respective analysis who presented with bone and tendon exposure or dead space, and reconstructed through individualized DIEP flaps in our department. We evaluated the appearance of donor site according to patients′satisfaction. Results: Eight patients had pedicle DIEP flaps, 47 patients were treated with free traditional DIEP flaps, and 38 cases underwent with special forms of DIEP flaps. The special forms of DIEP flaps included 8 chimeric DIEP flaps, 13 dual skin paddles DIEP flaps, 12 microdissection DIEP flaps, 1 conjoined DIEP flap, 2 flow-through DIEP flaps, 1 mutipaddles chimeric DIEP flap and 1 microdissection dual skin paddles DIEP. The size of flap ranged from 7 cm×4 cm to 36 cm×11 cm. All of the donor sites were primarily closed.Most of flaps survived, only two cases suffered with necrosis due to vascular crisis. Those patients have been followed-up from 5 to 24 months (average 12.4 months). A good color and texture were achieved in most of recipient sites. 16.1% of patients needed the second debulking procedure. The function of abdominal wall was normal postoperatively. Transverse flap design was performed for 32 patients, oblique design for 46 patients, irregular design for 13 patients, and longitudinal design for 2 patients. The rate of excellent donor site appearance was 86.9% in the transverse designed flaps, 70.0% for the donor site with the oblique designed flap, and 37.5% for the donor site with the irregular designed flap. Conclusions The individualized DIEP flaps based on different wound characteristics are ideal approaches for reconstruction of various types of soft tissue defects in extremities.

Objective To investigate the clinical efficiency of posterior tibial artery perforator pedicle propeller flaps for soft tissue coverage of the lower leg and foot defects.Methods From May,2008 to May,2016,30 cases with soft tissue defects of the lower leg and foot were cured by using posterior tibial artery perforator pedicle propeller flaps.The size of flaps ranged from 8.0 cm×4.0 cm to 24.0 cm×9.0 cm.Fascia flap was harvested in 5 cases,8 cases with deep fascia,and 6 cases with saphenous vein and saphenous nerve.The degree of flap rotation were from 160° to 180°.The donor sites were closed directly in 27 cases,and covered with skin grafting in 1 case,and with sequential flap in 2 cases.The shape,color,texture and satisfaction of the flaps were recorded during follow-up.Results Twenty-five flaps survived completely.The distal part of skin flap necrosis occurred in 3 cases and the wound healed well after dressing change.The distal part of flap necrosis occurred in 1 case,and free anterolateral thigh perforator flap was used to repair in the second phase.The complete necrosis of the flap occurred in 1 case,healing with scar after 2 months dressing treatment.All cases were followed-up from 4 months to 4.5 yeas (average 1.7 years).All flaps were smooth with a satis fied appearance and high patient satisfaction.Conclusion Posterior tibial artery perforator pedicle propeller flap which has reliable blood supply,less donor-site morbidities,cosmetic shape,simple operation and less postoperative complications,is an ideal method for soft tissue coverage of the lower leg and foot defects.