1.Long-term toxicity of fully humanized anti-human tumor necrosis factor-αmonoclonal antibody for injection in cynomolgus monkeys
Nan ZHANG ; Jiong WANG ; Yating ZHANG ; Gang SONG ; Shanshan ZHAN ; Yongbing PAN
Chinese Journal of Pharmacology and Toxicology 2015;(6):945-953
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.
2.A novel surgical technique for dissecting perforator vessel in anterolateral thigh perforator flap: Orderly retrograde four-side dissection
Juyu TANG ; Liming QING ; Panfeng WU ; Zhengbing ZHOU ; Fang YU ; Xiaoyang PANG ; Ding PAN ; Lei ZENG ; Yongbing XIAO ; Rui LIU
Chinese Journal of Microsurgery 2021;44(2):137-140
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.
3.Special forms of perforator flap in reconstruction of complex and exceptionally large defects of both lower extremities in child: A case report
Fang YU ; Juyu TANG ; Panfeng WU ; Xiaoyang PANG ; Lei ZENG ; Yongbing XIAO ; Ding PAN ; Liming QING ; Rui LIU
Chinese Journal of Microsurgery 2021;44(2):221-223
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.
4. Posterior tibial artery perforator pedicled propeller flaps for children heel injuries in spoke wheel accident
Juyu TANG ; Fang YU ; Panfeng WU ; Zhengbing ZHOU ; Yongbing XIAO ; Xiaoyang PANG ; Lei ZENG ; Ding PAN ; Liming QING ; Rui LIU
Chinese Journal of Plastic Surgery 2018;34(8):636-639
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.
5. Reconstruction of the soft-tissue defects of the limbs in children by free circumflex scapular artery perforator flap
Panfeng WU ; Juyu TANG ; Zhengbing ZHOU ; Fang YU ; Xiaoyang PANG ; Lei ZENG ; Ding PAN ; Yongbing XIAO ; Liming QING ; Rui LIU
Chinese Journal of Plastic Surgery 2018;34(9):698-704
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.
6. The clinical application of individual design deep inferior epigastric perforator flap for resurfacing the various types of soft tissue defects in extremities
Liming QING ; Juyu TANG ; Panfeng WU ; Zhengbing ZHOU ; Fang YU ; Xiaoyang PANG ; Ding PAN ; Lei ZENG ; Yongbing XIAO ; Rui LIU
Chinese Journal of Plastic Surgery 2018;34(9):709-714
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.
7.Repairation of large soft tissue defects of lower limbs with combined transplantation of bilateral perforator flap based on the descending branch of lateral circumflex femoral artery
Zhengbing ZHOU ; Juyu TANG ; Panfeng WU ; Fang YU ; Ding PAN ; Lei ZENG ; Yongbing XIAO ; Xiaoyang PANG ; Liming QING ; Rui LIU
Chinese Journal of Microsurgery 2020;43(6):535-539
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.
8.Specially formed radial collateral artery perforator flap in repair of complex defects of digits
Fang YU ; Juyu TANG ; Panfeng WU ; Zhengbing ZHOU ; Xiaoyang PANG ; Lei ZENG ; Yongbing XIAO ; Ding PAN ; Liming QING ; Rui LIU
Chinese Journal of Microsurgery 2021;44(4):364-368
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.
9.Anterolateral thigh chimeric perforator flap for repairing of large area compound tissue defect around knee joint
Panfeng WU ; Juyu TANG ; Da ZHONG ; Liming QING ; Xiaoyang PANG ; Fang YU ; Lei ZENG ; Ding PAN ; Yongbing XIAO ; Rui LIU ; Chenxiong HUANG
Chinese Journal of Microsurgery 2021;44(5):507-511
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.
10.Repairing of composite soft tissue defects in limbs with micro-dissected chimeric perforator flap pedicled with the descending branch of lateral circumflex femoral artery
Juyu TANG ; Yuling WANG ; Panfeng WU ; Fang YU ; Liming QING ; Ding PAN ; Xiaoyang PANG ; Lei ZENG ; Yongbing XIAO ; Rui LIU
Chinese Journal of Microsurgery 2021;44(6):621-624
Objective:To evaluate the feasibility and clinical results of micro-dissected chimeric (II-MCh) perforator flap based on the descending branch of lateral circumflex femoral artery(d-LCFA) for repairing composite soft tissue defects of limbs.Methods:From April, 2011 to December, 2019, a total of 19 cases of composite soft tissue defects of limbs combined with deep cavity were repaired with II-MCh perforator flap or micro-dissected thin lobulated (III-MPCh) perforator flap based on d-LCFA. The flap was micro-dissected before cut off the perforator. The deep dead cavity was filled with muscle flap, and the superficial wound was repaired with micro-dissected thin perforator flap. The sizes of flaps were 6.0 cm×3.0 cm-33.0 cm×8.0 cm. The muscle flaps were cut with volumes of 5.0 cm×3.0 cm×1.0 cm-13.0 cm×10.0 cm×1.5 cm. Donor sites of the flap were closed directly. Postoperative reviews were assigned at 1, 3, 6, 9 and 12 months. The appearance, colour, texture and recurrence of infection of the flap were checked and recorded.Results:Sixteen flaps survived successfully without necrosis and with primary healing at the donor sites. Two flaps had venous occlusion within 24 hours after surgery and healed after surgical exploration and venous anastomosis. One flap had arterial crisis within 24 hours after surgery and healed after surgical exploration and arterial anastomosis. All patients entered follow-up for 8-36 months with an average of 16 months. All recipient sites achieved satisfactory appearance and function, and only linear scars left at the donor sites.Conclusion:The II-MCh perforator flap based on d-LCFA is a special modality of anterolateral thigh perforator flap, which achieves a satisfying appearance at the recipient site by micro-dissecting the flap within one procedure. This emerging technique can effectively fill the dead cavity, and is an effective method to repair complex soft tissue defects of limbs combined with deep cavity.