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 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 feasibility and clinical effects of deep femoral artery third perforating artery perforator flap for reconstruction of soft tissue defect in lower limbs.Methods From September,2008 to October,2016,8 cases of soft tissue defect in lower limbs which were repaired by deep femoral artery third perforating artery perforator flap,including 4 cases of traffic accident trauma,2 cases of chronic ulcer,1 case of a fall injury,1 case of the scar after fracture operation.The area of wounds was 8.0 cm×7.0 cm-19.0 cm×8.0 cm.Seven patients were accompanied by different degrees of infections.The deep femoral artery third perforating artery perforator flap was designed to repair,including 5 cases of pedicled flaps and 3 cases of free flaps.The flap's appearance,color,texture,infection recurrence and the recovery of lower limb function were recorded at 1,3,6,9 and 12 months followed-up.Results One flap suffered partial necrosis due to cross-zone backflow disorder,the ipsilateral medial sural artery pedicled perforator flap was used to repair.The rest of the flaps survived successfully.Skin graft was used to close the donor site in 1 case,and other donor sites were closed directly.All patients had no postoperative hematoma or secondary infection.The followed-up periods ranged from 2 to 28 months (mean,8.1 months).All flaps had satisfied appearance and texture.There were no complications such as paresthesia and numbness in the donor sites.And no motion limitations in hip and knee joint of the operated leg.Conclusion Deep femoral artery third perforating artery perforator flap can be used for both free flaps and pedicled flaps,which is a feasible method to repair soft tissue defect in lower limbs.

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 efficiency and effect of radial collateral artery chimeric perforator flap combining a vascularized fragment of the distal humerus to reconstruct thumb complex defects. Methods: 5 cases of thumb complex tissue defects patients admitted to Xiangya Hospital of Central South University from June 2014 to October 2018. The patients were all male and aged from 35 to 63 years (average age was 47 years). There were 2 cases of right thumb and 3 cases of left thumb. The skin defect area was from 16.0 cm×4.0 cm to 3.5 cm×2.0 cm, and the bone defect length was 2-3 cm.All defects were reconstructed with radial collateral artery chimeric perforator flap combining a vascularized fragment of the distal humerus. The sizes of perforator flap were from 4 cm×2 cm to 18 cm×5 cm, and the sizes of bone were from 2.0 cm×0.6 cm×0.5 cm to 2.5 cm×1.0 cm×0.5 cm.The posterior branchial cutaneous of the arm was included in skin flap. 2 flaps underlied microdissect to defat. After fixing bone flap and finger/metacarpal bone with Kirschner wires, the radial accessory vessels were anastomosed with the radial vessels and cephalic vein at the nasopharyngeal fossa.All donor sites were closed directly. Results: All flaps survived uneventfully. Kirschner wires were removed 4 to 6 weeks after operation. Postoperative follow-up ranged from 3 months to 4.5 years (average 19 months). All bone aps healed without union. Functions of thumb opposition and thumb to finger were all good. The hand function had excellent result in 3 cases and good in 2 cases. Sensory recovered to S4 in 1 case, S3 in 3 cases and S2 in 1 case. Evaluation of the appearance satisfaction of patients was 5 points in 3 cases and 4 points in 2 cases. Conclusions The radial collateral artery chimeric perforator flap combining a vascularized fragment of the distal humerus, which can reconstruct skin soft tissue and bone simultaneously, has good postoperative feeling and function recovery, and satisfactory appearance, and is an effective method to repair the defect of thumb complex tissue.

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.