Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(Ⅳ)prodrug(C8Pt(Ⅳ))and Cet.The so-called antibody-platinum(Ⅳ)prodrugs conjugates,named Cet-C8Pt(Ⅳ),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(Ⅳ)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(Ⅳ)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(Ⅳ)prodrugs conjugates.

It is a common problem for all mentors to cultivate the capacity for scientific research of master degree candidates in plastic surgery under the current training program of "double-track in one" and "four-certificate in one". This study introduces the "COME" training mode that includes clinical study, off-hour, multiple modalities, and efficient feedback. This study elaborates the composition and method of this training mode, and compares the number and quality of published papers and thesis before and after its implementation. Results show that the "COME" training mode can significantly improve the capacity for scientific research of master degree candidates in plastic surgery.

It is a common problem for all mentors to cultivate the capacity for scientific research of master degree candidates in plastic surgery under the current training program of "double-track in one" and "four-certificate in one". This study introduces the "COME" training mode that includes clinical study, off-hour, multiple modalities, and efficient feedback. This study elaborates the composition and method of this training mode, and compares the number and quality of published papers and thesis before and after its implementation. Results show that the "COME" training mode can significantly improve the capacity for scientific research of master degree candidates in plastic surgery.

Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture (SPAC). However, application of external fixators is complex, and conventional two-dimensional (2D) imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry. The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models (3DPMs). In this study, patients coming from two centers were divided into two cohorts (3DPM group vs. control group) depending on whether a 3DPM was used for preoperative surgical planning. Operation duration, improvement in metatarsal-tibial angle (MTA), range of motion (ROM), the American Orthopedic Foot and Ankle Society (AOFAS) scores, complications, and patient-reported satisfaction were compared between two groups. The 3DPM group had significantly shorter operation duration than the control group ((2.0±0.3) h vs. (3.2±0.3) h,

Objective:To observe the effect of adipose tissue decellularized matrix hydrogel (DAT-gel) on the repair of sciatic nerve defect in rats.Methods:From April, 2019 to April, 2020, aseptic granular adipose tissue was collected from healthy adult women who underwent thigh or abdominal liposuction in the Department of Plastic Surgery, the First Medical Centre of the PLA General Hospital. Decellularisation and enzymatic digestion of adipose tissue were performed to prepare DAT-gel. Scanning electron microscope (SEM) was used to observe the ultrastructure of the hydrogel, and rheology was employed to test the gel dynamics and viscoelasticity of the hydrogel. A rat model of sciatic nerve defect was established and randomly divided into 3 groups: simple chitin catheter group (Chitin group), DAT-gel plus chitin catheter group (DAT-gel group) and autologous nerve reverse connection group (Autograft group) with 10 rats in each group. At the 12th week after surgery, the general view, function and morphology of the regenerated nerve were observed to evaluate the repairing status of the injured nerve. One-way analysis of variance (one-way ANOVA) was used for data analysis. If the difference between the groups was statistically significant, the Turkey method was further used for pairwise comparison. P<0.05 was considered as statistically significant. Results:The results of SEM showed that the DAT-gel had a three-dimensional structure in porous fibre network. The results of rheological test results showed that the complex viscosity of the hydrogel at 4 ℃ and 37 ℃ were 148.91 mPa·s and 801.29 mPa·s, respectively. DAT-gel underwent a sol-gel phase transition when the temperature had been increased. The results showed that DAT-gel had a good temperature-sensitive effect, and its critical point of sol-gel phase transition was similar to the internal temperature of rat. The results of animal experiments showed that the morphology and function of the regenerated nerve in the DAT-gel group were superior to Chitin group at 12 weeks after surgery, according to macroscopic view of the regenerated nerve, electrophysiology of the nerve, the morphology of the new axon and the target muscle, etc.. There was statistically significant between groups ( P<0.05). Conclusion:DAT-gel can significantly promote a repair of sciatic nerve defects in rats.

Objective:To investigate the effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats.Methods:The experimental research method was used. Fifty-one no matter male or female Sprague-Dawley rats aged 7-10 weeks were selected, and two round full-thickness skin defect wounds with a diameter of 2 cm were created on the back of each rat at a distance about 1.0 cm to the spine. The rats were divided into temperature-sensitive hydrogel group, gel group, and blank control group according to the random number table, with 17 rats and 34 wounds in each group. Wounds of rats in the first two groups were applied respectively with 0.3 mL temperature-sensitive hydroxybutyl chitosan hydrogel and carboxymethyl chitosan hydrogel immediately after injury, and the wounds of rats in blank control group received no treatment. The wounds of rats in the three groups were all covered with vaseline oil gauze. The states of temperature-sensitive hydroxybutyl chitosan hydrogel in wounds of rats in temperature-sensitive hydrogel group and carboxymethyl chitosan hydrogel in wounds of rats in gel group were observed every day when the dressings were changed, and the difficulty of vaseline oil gauze removal was recorded. On the 3rd, 7th, 10th, 14th, and 21st day after injury, the wound healing of rats in the three groups was observed and the wound healing rates were calculated. On the 3rd, 7th, 10th, 14th, and 21st day after injury, tissue from 4 wounds of 2 rats in each group was collected for the following observation and detection. The infiltration of inflammatory cells, angiogenesis, and re-epithelialization were observed by hematoxylin eosin staining. The regeneration and remodeling of collagen fibers were observed by Masson staining, and the collagen volume fraction was calculated. The expressions of interleukin-6 (IL-6), transforming growth factor β 1 (TGF-β 1), and matrix metalloproteinase-1 (MMP-1) were detected by enzyme-linked immunosorbent assay method. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni test. Results:The carboxymethyl chitosan gel in wounds of rats in gel group was liquid gel and could flow with the body position, while the temperature-sensitive hydroxybutyl chitosan hydrogel in wounds of rats in temperature-sensitive hydrogel group was solid gel and could not flow with the body position, and the distribution of the latter was more uniform. The vaseline oil gauzes were easily removed in wounds of rats in temperature-sensitive hydrogel group, while the vaseline oil gauzes were difficult to remove in the other two groups. On the 3rd, 7th, 10th, 14th, and 21st day after injury, the wound granulation tissue of rats grew well in temperature-sensitive hydrogel group and gel group, with no obvious infection, and two rats in blank control group died of wound infection on the 3rd and 5th day after injury. On the 7th, 10th, 14th, and 21st day after injury, the wound healing rates of rats in temperature-sensitive hydrogel group and gel group were significantly higher than that in blank control group ( P<0.01). On the 10th day after injury, the wound healing rate of rats in temperature-sensitive hydrogel group was significantly higher than that in gel group ( P<0.05). A large number of neutrophils and lymphocytes infiltrated into the wounds of rats in the three groups on the 3rd day after injury. The infiltration of inflammatory cells was gradually reduced and the wound healed gradually in rats of temperature-sensitive hydrogel group and gel group from the 7th to 21st day after injury, and the epidermis and dermis could be seen, without hair follicles and other skin appendages. The wounds of rats in blank control group did not heal completely on 21st day after injury. From the 3rd to 10th day after injury, the newly formed collagen fibers increased gradually in the wounds of rats in the three groups. On the 14th and 21st day after injury, the collagen fibers in the wounds of rats in temperature-sensitive hydrogel group and gel group were denser and more orderly than those in blank control group. On the 10th, 14th, and 21st day after injury, the collagen volume fraction of wounds of rats in temperature-sensitive hydrogel group and gel group was significantly higher than that in blank control group ( P<0.01). On the 14th day after injury, the collagen volume fraction of wounds of rats in temperature-sensitive hydrogel group was significantly higher than that in gel group ( P<0.01). On the 3rd, 7th, and 10th day after injury, the expressions of IL-6 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group ( P<0.01), and the expressions of IL-6 in wounds of rats in gel group were significantly lower than those in blank control group ( P<0.01). On the 3rd, 7th, and 10th day after injury, the expressions of TGF-β 1 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group ( P<0.01). The expressions of TGF-β 1 in wounds of rats in gel group were significantly lower than those in blank control group on the 3rd and 7th day after injury ( P<0.01), and the expression of TGF-β 1 in wounds of rats in gel group was significantly higher than that in blank control group on the 10th day after injury ( P<0.01). On the 14th day after injury, the expression of TGF-β 1 in wounds of rats in gel group was significantly higher than that in temperature-sensitive hydrogel group and blank control group ( P<0.01). On the 21st day after injury, the expression of TGF-β 1 in wounds of rats in temperature-sensitive hydrogel group was significantly lower than that in gel group and blank control group ( P<0.01), and the expression of TGF-β 1 in wounds of rats in gel group was significantly lower than that in blank control group ( P<0.01). On the 7th day after injury, the expression of MMP-1 in wounds of rats in gel group was significantly higher than that in temperature-sensitive hydrogel group and blank control group ( P<0.01). On the 10th, 14th, and 21st day after injury, the expressions of MMP-1 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group ( P<0.01). On the 10th day after injury, the expression of MMP-1 in wounds of rats in gel group was significantly lower than that in blank control group ( P<0.01). On the 14th and 21st day after injury, the expressions of MMP-1 in wounds of rats in gel group were significantly higher than those in blank control group ( P<0.01). Conclusions:Temperature-sensitive hydroxybutyl chitosan hydrogel can promote the healing of full-thickness skin defect wounds in rats by increasing the expressions of IL-6, TGF-β 1, and MMP-1, regulating the wound healing environment, inhibiting inflammatory reaction, improving the strength of tissue repair, and promoting collagen synthesis or decomposition

Objective:To investigate the clinical effect of water-jet excision combined with skin graft in the treatment of giant congenital melanotic nevus.Methods:The patients with giant nevus who were admitted to the Department of Plastic Surgery, Chinese PLA General Hospital from January 2015 to May 2019 were retrospectively analyzed. All patients were treated by layer-by-layer cutting of giant nevus with water-jet, preserving the subcutaneous fascial layer and part of the dermis as much as possible, then following by skin graft transplantation. The patients visited the hospital 1-2 years after operation. The postoperative scar of skin graft area was scored by Patient and Observer Scar Assessment Scale (POSAS), and the satisfaction of skin graft area was evaluated by digital scoring method (1-10 points). The recurrence of nevus pigmentosus and implantation metastasis were observed. Descriptive method were used for statistical analysis.Results:A total of 7 children were included, 2 males and 5 females, aged 4 to 14 years. There were 3 cases on the trunk and 4 cases on the extremities. Giant nevi accounted for (7.4 ± 3.1)% of the body surface area. Then skin graft survived well after surgery in all 7 children. During the 1-year follow-up after operation, the POSAS score of skin graft scar showed that the sum of 1-3 points in the scores of scar pain, itching, hardness and thickness by the patients or their families was 6, 4, 4 and 5 cases, respectively, and the sum of 4-10 points in the pigmentation and irregularity was 5 and 5 cases, respectively. None of the 7 patients had functional limitation in the skin graft area; the physicians’, scores for vascularity, pigmentation, thickness, and flexibility of the scars in the skin graft area were low, with a sum of 6, 3, 4, and 4 for the number of cases with 1-3 points and 2 and 4 for the number of cases with 1-3 points and 4-6 points in the flatness score, respectively. The satisfaction of both doctors and patients (sum of 7-10 points) was 4 and 5 cases, respectively. 7 cases were reexamined 1 year after operation, with recurrence of 2 punctate nevus pigmentosus(less than 1 mm in diameter) in only one case. No implantation metastasis in the skin graft area of nevus pigmentosus happened.Conclusions:Water-jet excision combined with skin graft in the treatment of giant nevus is simple and only one procedure required. The donor site only needs to cut a split-thickness skin graft. The postoperative scar is not obvious and the skin elasticity is better. Patients were relatively satisfied with the postoperative effect. It is suitable for the resection of nevus pigmentosus in the trunk especially the nevus pigmentosus with good texture and lighter color but not for the lesion at articular area of limbs.

Objective:To investigate the clinical effect of water-jet excision combined with skin graft in the treatment of giant congenital melanotic nevus.Methods:The patients with giant nevus who were admitted to the Department of Plastic Surgery, Chinese PLA General Hospital from January 2015 to May 2019 were retrospectively analyzed. All patients were treated by layer-by-layer cutting of giant nevus with water-jet, preserving the subcutaneous fascial layer and part of the dermis as much as possible, then following by skin graft transplantation. The patients visited the hospital 1-2 years after operation. The postoperative scar of skin graft area was scored by Patient and Observer Scar Assessment Scale (POSAS), and the satisfaction of skin graft area was evaluated by digital scoring method (1-10 points). The recurrence of nevus pigmentosus and implantation metastasis were observed. Descriptive method were used for statistical analysis.Results:A total of 7 children were included, 2 males and 5 females, aged 4 to 14 years. There were 3 cases on the trunk and 4 cases on the extremities. Giant nevi accounted for (7.4 ± 3.1)% of the body surface area. Then skin graft survived well after surgery in all 7 children. During the 1-year follow-up after operation, the POSAS score of skin graft scar showed that the sum of 1-3 points in the scores of scar pain, itching, hardness and thickness by the patients or their families was 6, 4, 4 and 5 cases, respectively, and the sum of 4-10 points in the pigmentation and irregularity was 5 and 5 cases, respectively. None of the 7 patients had functional limitation in the skin graft area; the physicians’, scores for vascularity, pigmentation, thickness, and flexibility of the scars in the skin graft area were low, with a sum of 6, 3, 4, and 4 for the number of cases with 1-3 points and 2 and 4 for the number of cases with 1-3 points and 4-6 points in the flatness score, respectively. The satisfaction of both doctors and patients (sum of 7-10 points) was 4 and 5 cases, respectively. 7 cases were reexamined 1 year after operation, with recurrence of 2 punctate nevus pigmentosus(less than 1 mm in diameter) in only one case. No implantation metastasis in the skin graft area of nevus pigmentosus happened.Conclusions:Water-jet excision combined with skin graft in the treatment of giant nevus is simple and only one procedure required. The donor site only needs to cut a split-thickness skin graft. The postoperative scar is not obvious and the skin elasticity is better. Patients were relatively satisfied with the postoperative effect. It is suitable for the resection of nevus pigmentosus in the trunk especially the nevus pigmentosus with good texture and lighter color but not for the lesion at articular area of limbs.

Objective:This study is to investigate the parameter settings and imaging effects of Micro-CT scanning externalmalignancies during operation and summarize the characteristics of Micro-CT images regarding external soft tissue and tumors.Methods:According to the inclusion criteria, patients with externalmalignancies admitted to the Department of Plastic and Reconstructive Surgery of the First Medical Center of the PLA General Hospital from October 2018 to January 2020 were collected. Through the surgical resection of tumors, the isolated tumor specimens were divided into appropriate sizes (length × width × thickness not exceeding 5 cm×3 cm×3 cm), placed on the Micro-CT scanning bed, and scanned with different parameters. (1) Scanning with different times: with the fixedscanning voltage (50 kV for sarcoma, 70 kV for other tumors), the same specimen was scanned with 4min and 14min protocols respectively. (2) Scanning with different voltages: with the fixed scanning time (4 min), the same specimen was scanned with 30, 50, 70, and 90 kV voltages respectively. After comparing the imaging results with different scanning times and different scanning voltages, the optimal scanning parameters for different tumors were obtained. (3) The regions of interest for radiology were taken from the specimens, and pathological HE stained slides were prepared. Digital slices were obtained by precice automatic digital slice scanning system. The slices were compared with Micro-CT corresponding cross-sectional images and the radiological characteristics of different tissues were recorded.Results:A total of 27 patients were included/incorporated into the study and there were 15 males and 12 females, aged from 33 to 82, with an average age of 63.9 years old, including 16 cases of skin squamous cell carcinoma, 2 cases of basal cell carcinoma, and 2 cases of extramammary Paget′s disease, 1 case of melanoma, 3 cases of cutaneous fibrosarcoma, 1 case of angiosarcoma, and 2 cases of liposarcoma. A total of 65 groups were compared between Micro-CT images and pathology slides. (1) Scanning time: both 4 min and 14 min scanning times can obtain clear images which can meet requirements for morphology observation and identification of margins of tumors. (2) Scanning voltage: as for squamous cell carcinoma, the quality of images obtained by the scanning voltage of 30 and 50 kV is poor, while by the voltage of 70 and 90 kV is high. As for sarcoma, the quality of images obtained by the scanning voltage of 30 kV is poor; by the voltage of 50 kV is high and the contrast between tumor and subcutaneous fat is low by the scanning voltage of 70 and 90 kV. (3) The radiological morphology of external tumors and surrounding tissues are similar with the pathology slides. The boundary between skin and subcutaneous tissue is clear and the hair follicles are clearly distinguishable. The radiological characteristics of tumors are related to the type of tumors and the density of tumors, including high-density shadows, thicker than normal skin, no hair follicles and some small calcification points. The boundary between squamous cell carcinoma or sarcoma and normal skin or subcutaneous can be distinguished. As for the tumors in the skin, such as basal cell carcinoma, extra-mammary Paget′s disease, etc. the imaging results are poor.Conclusions:The Micro-CT scanning parameters need to be set according to the type of the tumor. The scanning time has little effect on the evaluation of the tumor. It is recommended to choose the protocol of 4 min during operation. The recommended scanning voltage of squamous cell carcinoma is 70 kV and the voltage of sarcoma is 50 kV. Micro-CT can clearly imaging the skin structure of soft tissue specimens on the body surface; configuration is identifiable for tumors that invade beyond skin and have a large heterogeneity of density compared with surrounding tissues; for tumors that do not exceed the dermis, the imaging effect is not good.

Objective:This study is to investigate the parameter settings and imaging effects of Micro-CT scanning externalmalignancies during operation and summarize the characteristics of Micro-CT images regarding external soft tissue and tumors.Methods:According to the inclusion criteria, patients with externalmalignancies admitted to the Department of Plastic and Reconstructive Surgery of the First Medical Center of the PLA General Hospital from October 2018 to January 2020 were collected. Through the surgical resection of tumors, the isolated tumor specimens were divided into appropriate sizes (length × width × thickness not exceeding 5 cm×3 cm×3 cm), placed on the Micro-CT scanning bed, and scanned with different parameters. (1) Scanning with different times: with the fixedscanning voltage (50 kV for sarcoma, 70 kV for other tumors), the same specimen was scanned with 4min and 14min protocols respectively. (2) Scanning with different voltages: with the fixed scanning time (4 min), the same specimen was scanned with 30, 50, 70, and 90 kV voltages respectively. After comparing the imaging results with different scanning times and different scanning voltages, the optimal scanning parameters for different tumors were obtained. (3) The regions of interest for radiology were taken from the specimens, and pathological HE stained slides were prepared. Digital slices were obtained by precice automatic digital slice scanning system. The slices were compared with Micro-CT corresponding cross-sectional images and the radiological characteristics of different tissues were recorded.Results:A total of 27 patients were included/incorporated into the study and there were 15 males and 12 females, aged from 33 to 82, with an average age of 63.9 years old, including 16 cases of skin squamous cell carcinoma, 2 cases of basal cell carcinoma, and 2 cases of extramammary Paget′s disease, 1 case of melanoma, 3 cases of cutaneous fibrosarcoma, 1 case of angiosarcoma, and 2 cases of liposarcoma. A total of 65 groups were compared between Micro-CT images and pathology slides. (1) Scanning time: both 4 min and 14 min scanning times can obtain clear images which can meet requirements for morphology observation and identification of margins of tumors. (2) Scanning voltage: as for squamous cell carcinoma, the quality of images obtained by the scanning voltage of 30 and 50 kV is poor, while by the voltage of 70 and 90 kV is high. As for sarcoma, the quality of images obtained by the scanning voltage of 30 kV is poor; by the voltage of 50 kV is high and the contrast between tumor and subcutaneous fat is low by the scanning voltage of 70 and 90 kV. (3) The radiological morphology of external tumors and surrounding tissues are similar with the pathology slides. The boundary between skin and subcutaneous tissue is clear and the hair follicles are clearly distinguishable. The radiological characteristics of tumors are related to the type of tumors and the density of tumors, including high-density shadows, thicker than normal skin, no hair follicles and some small calcification points. The boundary between squamous cell carcinoma or sarcoma and normal skin or subcutaneous can be distinguished. As for the tumors in the skin, such as basal cell carcinoma, extra-mammary Paget′s disease, etc. the imaging results are poor.Conclusions:The Micro-CT scanning parameters need to be set according to the type of the tumor. The scanning time has little effect on the evaluation of the tumor. It is recommended to choose the protocol of 4 min during operation. The recommended scanning voltage of squamous cell carcinoma is 70 kV and the voltage of sarcoma is 50 kV. Micro-CT can clearly imaging the skin structure of soft tissue specimens on the body surface; configuration is identifiable for tumors that invade beyond skin and have a large heterogeneity of density compared with surrounding tissues; for tumors that do not exceed the dermis, the imaging effect is not good.