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.

To investigate the feasibility and clinical efficacy of free graft of vascularized iliac bone flap based on deep iliac circumflex vessels for the treatment of osteonecrosis of femoral head (ONFH). Methods Twelve cases of ONFH(13 hips) received free graft of vascularized iliac bone flap based on deep iliac circumflex ves-sels from April, 2016 to July, 2017.The average Harris score was (74.7±6.9) in the second stage and (68.6±9.2) in the third stage. After debriding the necrosis bone of the femoral head, the contralateral vascularized iliac bone flap had been harvested, and then implanted into the femoral head. The deep iliac circumflex artery and its accompanying vein were anastomosed with the transverse branch (or ascending branch) of the lateral circumflex femoral artery and con-comitant vein respectively. The herringbone brace was used for hip fixation for 3 weeks after operation. X-ray exami-nation (1, 3, 6, 9 and 12 months after operation, respectively) and Harris hip score (6 and 12 months after operation, respectively) were performed to evaluate the recovery results of the femoral head. Scores were recorded and analyzed by paired t-test.The difference was considered to statistically significant if P＜0.05. Results The patients were fol-lowed-up for 15(12-20)months. The iliac bone flap of 12 patients (13 hips) healed well. There was no necrosis and collapse in 12 hips, except 1 femoral head collapsed slightly because of weight loading too early. The average Harris score was (91.6±4.5) of the second stage and (84.8±6.1) of the third stage. Compared with scores before the operation, the difference was statistically significant (P＜0.05). Conclusion Free vascularized iliac bone grafting based on deep iliac circumflex vessels is an ideal treatment for ONFH head in middle and advanced stage.

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 investigate the feasibility and clinical effect of combined transplantation of bilateral perforator flap based on the descending branch of lateral circumflex femoral artery in the reconstruction of large soft tissue defects of lower limbs.Methods:From January, 2014 to September, 2019, 35 cases of large soft tissue defects of lower limbs were repaired by combined transplantation of bilateral perforator flap based on the descending branch of lateral circumflex femoral artery, and the donor sites were directly closed. The wound involved the shank, ankle and foot; The areas of defect ranged from 17.0 cm×12.0 cm to 33.0 cm×18.0 cm. External fixation were performed on 19 cases with open comminuted tibia fracture, and flap transplantation was preformed after through debridement and negative-pressure wound therapy for 5-7 days. The lateral femoral cutaneous nerve was remained in the flap, which was anastomosed with sensory nerves in the recipient site. The colour, texture, sensation, secondary ulcer of the flap and limb function were followed-up after the operation.Results:Of the 35 cases, 34 cases completely survived, and necrosis occurred in 1 case. The donor sites were closed primarily and complication was not observed in any of the cases. The followed-up period ranged from 6 to 38 months, at 17.6 months in average. The appearance and function of the reconstructed lower limbs were satisfactory.Conclusion:The combined transplantation of the perforate flap of descending branch of lateral femoral circumflex artery is safe and reliable. It can be used to repair large defect and the damage of the donor site is limited. It is an effective method to repair large area of soft tissue defects of lower limbs.

Objective:To explore the effects of specially formed radial collateral artery perforator flaps in reconstruction of the complex digit defects.Methods:From April, 2014 to March, 2020, 20 patients with multiple digit injuries combined with bone defects were treated by digit reconstruction with radial collateral artery chimeric and polyfoliate perforator flaps. Of the 20 patients, 7 patients were treated by chimeric perforator flaps, 12 by polyfoliate perforator flaps and 1 by chimeric polyfoliate perforator flap. Altogether 28 perforator flaps and 13 bone flaps were taken. The size of perforator flaps were 9.5 cm×4.0 cm to 4.0 cm×2.0 cm, and bone flap were 1.5 cm×0.6 cm×0.6 cm to 2.5 cm×1.0 cm×0.6 cm. All the donor sites were closed directly. Regular follow-up was performed. Function and clinical effect evaluation of repaired digits were made according to the Standard for Upper Limb Function Assessment of Hand Surgery Society of Chinese Medical Association and Sensory Function Assessment Criteria of British Medical Research Council (BMRC).Results:Twenty-seven flaps survived without any event. Venous congestion occurred in 1 flap with partial skin necrosis. Postoperative follow-up lasted from 3 months to 3.5 years (average 17.5 months). The appearance and texture of all flaps were good. All bone flaps properly healed. Sensory recovery achieved S 4 in 8 flaps, S 3 in 16 flaps and S 2 in 4 flaps. Hand function evaluation showed excellent in 12 patients and good in 8 patients. Conclusion:The specially formed radial collateral artery perforator flaps have the features of various designs with reliable blood supply, and are effective in repair of multiple digit injuries combined with soft tissue and bone defects.

Objective:To investigate the feasibility and clinical efficacy of anterolateral thigh chimeric perforator flap in repair of large area soft tissue defects around the knee joint.Methods:From January, 2015 to October, 2019, 9 patients with large area soft tissue defects around the knee joint were treated. All patients had different degrees of defect in knee joint capsule and joint opening. Before operation, the width of the flap was determined by "skin lifting and kneading test", and the location of perforators in anterolateral femoral region was confirmed and marked with the assistance of HHD detector. According to the size and shape of the wound surface, single leaf or lobulated perforator flap was designed based on the principle that the donor site should be closed directly. The minimum size of the flap was 14.0 cm×5.0 cm, there was 1 case of lobulated flap with the largest area, respectively was 17.0 cm×9.0 cm and 18.0 cm×8.5 cm. The chimeric tissue flap(muscle flap or fascia lata flap) was taken according to the location and severity of joint opening. The grafted tissue flap was used to fill the articular cavity, the flap was used to repair the wound of knee joint, the blood supply of the flap was reconstructed, and a drainage catheter was placed in the cavity of knee joint. The recovery follow-up conducted in outpatient department.Results:All flaps survived without vascular incident. The recipient site of flap in 1 patient was not thoroughly washed and drained, and there was more exudation. After dressing change and drainage, the rest recipient areas of the flap were healed in stage I. All patients entered 3 to 36(average 12) months of follow-up. The appearance and function of recipient area recovery were satisfactorily. Only a linear scar remained in donor site.Conclusion:Anterolateral thigh chemeric perforator flap is ideal for repairing large soft tissue defects around the knee joint.

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.