1.Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4Pathway via the p300-p53 Axis
Xinyan HUANG ; Wenxi WANG ; Songzhao ZHANG ; Lili LI ; Jihui HUANG
Biomolecules & Therapeutics 2025;33(2):365-377
The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.
2.Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4Pathway via the p300-p53 Axis
Xinyan HUANG ; Wenxi WANG ; Songzhao ZHANG ; Lili LI ; Jihui HUANG
Biomolecules & Therapeutics 2025;33(2):365-377
The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.
3.Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4Pathway via the p300-p53 Axis
Xinyan HUANG ; Wenxi WANG ; Songzhao ZHANG ; Lili LI ; Jihui HUANG
Biomolecules & Therapeutics 2025;33(2):365-377
The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.
4.Glutamate Receptor Antagonists Attenuate Stereotyped Behaviors via Modulating BDNF Levels in Obsessive-complusive Disorder Model Mice
Weijie WANG ; Yuchong LUO ; Dongmiao HUANG ; Chen YANG ; Jihui YUE ; Xianglan WANG ; Shenglin WEN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):475-485
ObjectiveTo explore whether fluoroethylnormemantine (FENM), an NMDA receptor antagonist, could improve compulsive-like behaviors and to investigate its underlying mechanisms in the RU24969-induced obsessive-compulsive disorder (OCD) mouse model. MethodsThirty-two mice were randomly assigned to four groups: Saline (n=8), RU24969 (n=8), RU+FENM (n=8), and FENM (n=8). Mice received FENM or an equivalent volume of saline for pre-treatment, followed by RU24969 or saline for model induction 30 minutes later. Behavioral tests were performed 1 hour after modeling, and serum samples were collected to measure the level of brain-derived neurotrophic factor (BDNF). Evans Blue dye was intravenously injected to assess dye content in brain tissue, thereby evaluating potential blood-brain barrier damage. ResultsFENM treatment significantly improved repetitive stereotyped circling behavior (F=39.850, P<0.001) and alleviated persistent motor activity (F=50.200, P<0.001) in RU24969 model mice. Additionally, FENM treatment significantly increased serum BDNF level in RU24969-induced OCD mice (F=18.930, P<0.001). ConclusionsFENM , an NMDA receptor antagonist, may alleviate compulsive behaviors in OCD mice by modulating BDNF levels , thereby exerting anti-compulsive effects. Neither the RU24969 model nor FENM treatment significantly affectes blood-brain barrier integrity.
5.Techniques and clinical effects of digit-tip replantation in children with anastomosis of superior digital arch artery
Sheng XIONG ; Yongjiang LYU ; Jinghui HUA ; Xiaolong HUANG ; Guiyang WANG ; Ruixing HOU ; Jihui JU
Chinese Journal of Microsurgery 2024;47(1):65-70
Objective:To investigate the techniques of digit-tip replantation with anastomosis of superior digital arch artery in children and to evaluate the clinical effects.Methods:From January 2020 to September 2022, 62 children (62 digits) with completely severed digit-tips were admitted to the Department of Paediatric Orthopaedics, Suzhou Ruihua Orthopaedic Hospital. All the injury planes were distal to the nail root. All arterial dissections were distal to the digital arterial arch with the vessel calibre from 0.15 mm to 0.35 mm. The superior arch arteries of the digital arterial arch were successfully anastomosed. After surgery, a significant blood flux to the replanted digit body were observed. Postoperative necroses or failures were analysed for the causes. All children with survived digit-tips were entered into scheduled follow-ups through a combination of visit of outpatient clinics or via WeChat and telephone reviews. Postoperative follow-up included digit body fullness, motion of distal interphalangeal joint, nail growth, scarring, and response of the replanted digit-tips to needling. Clinical outcomes were evaluated according to the evaluation criteria for finger replantation function.Results:Of the 62 replanted digit-tips, 56 survived after replantation. Two digits had wound infection after surgery, and survived by dressing change and applying sensitive antibiotics. Necrosis occurred in 6 replanted digit-tips, of which 2 necrotic digit bodies were amputated, and the stumps at the distal interphalangeal joint were repaired. The other 4 necrotic digits were healed after dressing change under the scab due to a smaller digit body. A total of 52 children (including 2 survivals from postoperative infection after dressing changes and 4 survivals with healing underneath-eschar after necrosis) and with 10 lost during follow-up (including 2 with stump repairs after necrosis). The follow-up period ranged from 2 to 30 months, with an average of 6 months. The shape and function of replanted digit-tips recovered well. According to the evaluation criteria for finger replantation function, 44 digits were of excellent, 6 of good, and 2 of fair.Conclusion:In children, the superior arch arteries of digital arterial arches of the digit-tips are small in diameter. However, the vessels in smaller calibres can be anastomosed, should proper surgical techniques are applied. Therefore, due to the satisfactory outcomes, microsurgeons should try the best efforts to replant a digit severed at the plane of digit-tip.
6.Application of highly selective arterial indocyanine green angiography in the design of anterolateral thigh free flap
Shi WANG ; Shuai DONG ; Yang CAO ; Guiyang WANG ; Chengpeng YANG ; Fengwen SUN ; Yongtao HUANG ; Liping GUO ; Liang YANG ; Rong ZHOU ; Jihui JU
Chinese Journal of Burns 2024;40(10):948-954
Objective:To introduce the application of highly selective arterial indocyanine green angiography (hereinafter referred to as highly selective arterial angiography) in the design of anterolateral thigh free flap.Methods:This study was a retrospective observational study. From November 2023 to April 2024, 29 patients with wounds in extremities which were repaired by anterolateral thigh free flaps designed under the assistance of highly selective arterial angiography and met the inclusion criteria were admitted to the Department of Hand Surgery and Department of Wound Repair Surgery of Suzhou Ruihua Orthopedic Hospital, including 26 males and 3 females, aged 16 to 71 years. The wound area after debridement ranged from 8.0 cm×4.5 cm to 27.0 cm×16.0 cm. During the surgery, highly selective arterial angiography was used to assist in flap design. The fluorescence development range of the source arteries or perforators of flaps was observed. The blood supply range of the source arteries or perforators of flaps was determined based on the fluorescence development of the skin, and the excision position of the flap was adjusted. The flap incision area ranged from 9.0 cm×6.0 cm to 29.0 cm×16.0 cm. During the surgery, the number of highly selective arterial angiography, the type of source artery of perforators for puncture, and changes in the excision position of flaps were observed and recorded. After surgery, the blood supply and survival of flaps, the healing of wounds and the survival of skin grafts in the flap donor sites, and the angiography-related complications were observed.Results:All the 32 flaps of 29 patients were successfully excised. The highly selective arterial angiography was performed 37 times, including 13 cases of puncture of the oblique branch of the lateral circumflex femoral artery, 6 cases of puncture of the descending branch, 8 cases of double puncture of the oblique and descending branches, and 2 cases of puncture of arteries from other branches. During the surgery, the excision position of 28 flaps did not change, the excision position of 3 flaps moved towards proximal extremity of the thigh, and the excision position of 1 flap moved towards distal extremity of the thigh. All the flaps survived successfully after the surgery, and there was no partial necrosis of the flaps at the proximal or distal ends. The wounds in the flap donor sites healed, and all skin grafts survived. No angiography-related complications occurred.Conclusions:Highly selective arterial angiography can be used to determine the blood supply range of the source artery and perforators of the anterolateral thigh free flaps during the surgery. It can evaluate the blood supply of flaps more intuitively and objectively. Its application in assisting flap design can avoid partial flap necrosis caused by unreasonable preoperative design to a certain extent, and it is safe and reliable.
7.Application of "ABC" three line perforator locating method for free anterolateral perforator flap of calf
Tao ZHANG ; Lin YANG ; Junnan CHENG ; Shengzhe LIU ; Zhijin LIU ; Yongtao HUANG ; Qinfeng GAO ; Fengwen SUN ; Chengpeng YANG ; Jihui JU
Chinese Journal of Microsurgery 2023;46(1):70-75
Objective:To explore the feasibility of an "ABC" three line perforator locating method in design and harvest of free anterolateral perforator flap of calf.Methods:Between March 2021 and November 2021, 42 patients with 62 wounds on hand and foot were treated in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. The "ABC" three line perforator locating method was applied to determine the location and source of perforating branch before operation and to guide the design and harvest of flap during operation in wound reconstruction. Among the 42 patients, 24 had the injury of single digit, 7 had the injuries with 2 digits, 4 with 3 digits, 1 with 4 digits, 1 of the first web, 1 in the wrist, 2 of the great toe, 1 of second toe and 1 in dorsal foot. The sizes of soft tissue defect were 1.5 cm×2.0 cm-3.0 cm×14.0 cm. The sizes of the flaps were 2.0 cm×2.5 cm-3.5 cm×15.0 cm. All donor sites were sutured directly. In the follow-up, sensations of flaps were evaluated following the sensory function evaluation standard of British Medical Research Council(BMRC), and the recovery of the donor and recipient sites was evaluated by the flap comprehensive evaluation scale. Regular follow-up were scheduled at outpatient clinic.Results:A total of 162 perforators were located before operation. There were 95 perforating branches being explored in the operation, of which 5 patients had 1 extra perforating branch than that located before surgery. Seventy-six perforating branches were found consistent with preoperative localisation, with a coincidence rate of 84.4%(76/90). Sixty-four perforating branches were found consistent with the preoperative source with an accuracy rate of 84.2%(64/76). All the 62 flaps survived without a vascular compromise. Follow-up lasted for 6-10(mean 7.1) months. The colour and texture of the flaps were excellent. The flaps were thin and wear-resistant. The sensory function of the flaps was evaluated at S 1-S 3 by BMRC. Comprehensive evaluation scale of flap was excellent in 38 patients and good in 4 patients. Conclusion:"ABC" three line perforator locating method in design of free anterolateral calf flap is a feasible and an ideal auxiliary method in surgical practice. It combines anatomical knowledge, clinical experience and Doppler ultrasound localisation as well as accurately guides the location and source prediction of perforator before surgery.
8.Comparison of robot-assisted and free-hand percutaneous cannulated screwing for femoral neck fractures in the middle-aged and young patients
Fuming HUANG ; Xinzhe ZHANG ; Weixiong LI ; Rui CHEN ; Kaijun LIANG ; Haiqiao XU ; Haizhou HUANG ; Jihui ZHOU ; Shibang LIN
Chinese Journal of Orthopaedic Trauma 2023;25(11):979-985
Objective:To compare the clinical efficacy between robot-assisted and free-hand percutaneous cannulated screwing (PCS) in the treatment of femoral neck fractures in the middle-aged and young patients.Methods:A retrospective study was conducted to analyze the clinical data of 53 patients with femoral neck fracture who had been treated with PCS from May 2020 to May 2022 at Department of Traumatic Surgery, Maoming Hospital Affiliated to Southern Medical University. In the robot group of 25 patients subjected to robot-assisted PCS, there were 11 males and 14 females with an age of (48.2 ± 11.9) years; in the free-hand group of 28 patients subjected to free-hand PCS, there were 13 males and 15 females with an age of (48.5 ± 9.8) years. The 2 groups were compared in terms of operation time, intraoperative bleeding, intraoperative guide drills, intraoperative fluoroscopy frequency, fracture union time, Harris hip score at the last follow-up and postoperative complications. Postoperative imaging examination was performed to evaluate distribution accuracy of the cannulated screws in the femoral neck (deviation between the screws and the femoral neck axis, parallelism between the screws and distance between the screws and the neck cortex).Results:There was no statistically significant difference between the robot and free-hand groups in the general clinical data before operation, showing comparability ( P>0.05). The robot group showed significantly shorter operation time [(32.7 ± 4.8) min], significantly less intraoperative bleeding [(14.6 ± 4.8) mL], significantly less intraoperative guide drillings [(3.5 ± 0.7) times] and significantly less intraoperative fluoroscopy frequency [(7.9 ± 1.4) times] than the free-hand group [(56.9 ± 11.3) min, (27.0 ± 7.3) mL, (9.1 ± 1.8) times and (16.3 ± 6.0) times)] (all P<0.05). Postoperative imaging showed that the deviation between the screws and the femoral neck axis was 4.4° ± 1.1° on the anteroposterior X-ray film and 3.2° ± 0.8° on the lateral X-ray film, the parallelism between the screws 4.9° ± 0.8° on the anteroposterior X-ray film and 3.0° ± 0.7° on the lateral X-ray film, and the distance between the screws and the femoral neck cortex (10.4 ± 2.7) mm in the robot group, all significantly smaller than those in the free-hand group [10.5° ± 2.8°, 4.9° ± 1.1°, 12.1° ± 4.0°, 5.1° ± 1.3°, and (15.4 ± 3.2) mm] (all P<0.05). All the 53 patients were followed up for (22.2 ± 8.5) months. All fractures got united. The fracture union time in the robot group [(20.6 ± 4.6) weeks] was insignificantly shorter than that in the free-hand group [(23.7 ± 7.7) weeks] ( P>0.05). At the last follow-up, the Harris hip score in the robot group [(88.6 ± 5.6) points] was significantly higher than that in the free-hand group [(84.8 ± 6.3) points] ( P<0.05). Follow-ups revealed 2 cases of internal fixation loosening, 1 case of screw head cutting and 1 case of femoral head necrosis in the free-hand group but none of such complications in the robot group. Conclusion:In the treatment of femoral neck fractures in the middle-aged and young patients, compared with free-hand PCS, robot-assisted PCS shows advantages of shorter intraoperative time, less bleeding, less fluoroscopic radiation, higher accuracy of screw placement, a lower incidence of postoperative complications and better functional recovery of the hip joint.
9.Effects of bilobated superficial peroneal artery perforator flap in repairing two adjacent wounds of the fingers
Tao ZHANG ; Junnan CHENG ; Lin YANG ; Fengwen SUN ; Qinfeng GAO ; Yongtao HUANG ; Chengpeng YANG ; Yang CAO ; Zhijin LIU ; Jihui JU
Chinese Journal of Burns 2023;39(7):655-661
Objective:To investigate the therapeutic efficacy of bilobated superficial peroneal artery perforator flap in repairing two adjacent wounds of the fingers.Methods:A retrospective observational study was conducted. From January 2021 to January 2022, 15 patients with two adjacent wounds of the fingers who met the inclusion criteria were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 10 males and 5 females, aged 25 to 51 years. The area of single wound after debridement was from 2.5 cm×2.0 cm to 7.5 cm×2.5 cm. All the wounds were repaired by the bilobated superficial peroneal artery perforator flap from the lower leg. The single lobe area of bilobated flap was from 3.0 cm×2.0 cm to 8.0 cm×3.0 cm. The wounds in all the donor sites were sutured directly. During the operation, the number of resected flaps, the number and type of carried perforators were recorded, and the calibers of perforator and superficial peroneal artery and the length of vascular pedicle were measured. The survival of flap and the wound healing in the donor and recipient sites were recorded after operation. The recovery of donor and recipient sites were recorded during follow-up. At the last follow-up, the repair effect of flap was evaluated by the comprehensive evaluation scale, and the sensory function of flap was evaluated by the sensory function evaluation standard of British Medical Research Association.Results:During the operation, 15 bilobated flaps were successfully resected, carrying 36 superficial peroneal artery perforators, all of which were septocutaneous perforators with the caliber of 0.2-0.8 mm. The caliber of superficial peroneal artery was 0.4-1.1 mm and the length of vascular pedicle was 3-8 cm. After operation, all the flaps survived with no vascular crisis occurred, and the wounds in donor and recipient sites healed well. During the follow-up of 6 to 12 months, the color and texture of flaps were similar to those of normal tissue in the hand and the appearance of flap was good in 10 cases; the other 5 cases underwent the stage Ⅱ flap thinning and plastic surgery 6 months after operation due to the bloated appearance of flaps. There was only linear scar in the donor site of lower leg, with no obvious scar hyperplasia or pigmentation, and there was no obvious adverse effect on the sensation or motor function of the distal limbs in the donor area. At the last follow-up, the repair effect of flap of 15 patients was excellent in 11 cases and good in 4 cases, and the sensory function of the flap was evaluated as grade S 2 in all cases. Conclusions:The bilobated superficial peroneal artery perforator flap has high proportion of septocutaneous perforator, and the blood supply is sufficient and reliable. Using this flap to repair two adjacent wounds of the fingers causes minimal damage to the donor area, only one group of blood vessels is needed to be anastomosed to repair two wounds, the difficulty of microoperation is reduced, and good flap repair effect and sensory function can be obtained.
10.Clinical effects of anterolateral thigh flap with blood supply source of medial femoral perforator in repairing the wounds on extremities
Chengpeng YANG ; Linfeng TANG ; Zhijin LIU ; Shengzhe LIU ; Lin YANG ; Junnan CHENG ; Tao ZHANG ; Fengwen SUN ; Yongtao HUANG ; Qinfeng GAO ; Jihui JU
Chinese Journal of Burns 2023;39(9):842-848
Objective:To investigate clinical effects of anterolateral thigh flap with blood supply source of medial femoral perforator in repairing the wounds on extremities.Methods:A retrospective observational study was conducted. From October 2018 to June 2021, Suzhou Ruihua Orthopedic Hospital admitted 12 patients (11 males and 1 female, aged 24-64 years) who met the inclusion criteria, and did not have the lateral circumflex femoral artery during anterolateral thigh flap resection, or changed to medial femoral perforator as a source of blood supply due to small perforator to repair the wound with flap transplantation. The wounds were on the upper limbs in 7 cases and on the lower limbs in 5 cases. The wound area after debridement was 8.0 cm×5.0 cm-24.0 cm×6.5 cm, and the applied flap area was 9 cm×6 cm-25 cm×7 cm. During transplantation, the perforating branch or source artery of the flap was anastomosed end to end with the vascular pedicle of the recipient area. Subcutaneous beauty suture was performed on all the donor wounds. After operation, the survival of the flap and vascular crisis were observed; and the wound healing at the donor site was observed. During follow-up, the texture of the flap and complications at the donor site were observed. At the last follow-up, the effect of flap repair was evaluated by using the modified self-made comprehensive efficacy rating table.Results:After operation, all the flaps of patients survived without vascular crisis; the wounds in the donor site healed smoothly. During follow-up of 6 to 26 months, the flaps had good texture; only linear scars remained in the donor area without scar contracture, pain or other discomfort. At the last follow-up, the total score of flap repair effect of 12 patients was 75-95, with an average of 87, of which 5 cases were rated as excellent, 6 cases as good, and 1 case as fair, and the proportion of excellent and good patients was 11/12.Conclusions:The application of anterolateral thigh flap with blood supply from the medial femoral perforator to repair wounds on extremities is an alternative method for the vascular variations such as no descending branch, oblique branch, or small perforator of the lateral circumflex femoral artery during the resection of the anterolateral thigh flap. This operation has the advantages of simple operation, small trauma, and others, which effectively ensures the smooth operation.

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