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.Design of anterolateral thigh perforator flap aided by three-dimensional printing technique for repairing irregular extremity wounds
Chengwei GE ; Guodong JIANG ; Kai WANG ; Zhigang CHE ; Junnan CHENG ; Zhicheng TENG ; Song YUAN ; Jihui JU
Chinese Journal of Plastic Surgery 2024;40(9):946-953
		                        		
		                        			
		                        			Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.
		                        		
		                        		
		                        		
		                        	
7.Effects of the first dorsal metatarsal artery terminal branch flaps in repairing skin and soft tissue defects of fingers
Haibo WU ; Guangzhe JIN ; Jin LI ; Yan ZHANG ; Kai WANG ; Qiang WANG ; Xiaoqiang TANG ; Jihui JU ; Ruixing HOU
Chinese Journal of Burns 2024;40(10):963-970
		                        		
		                        			
		                        			Objective:To explore the effects of the first dorsal metatarsal artery terminal branch flaps in repairing skin and soft tissue defects of fingers.Methods:The study was a retrospective observational study. From October 2021 to December 2022, 44 patients with skin and soft tissue defects in 55 fingers who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital. There were 39 males (48 fingers) and 5 females (7 fingers), aged 18 to 54 years. The single wound area after debridement ranged from 1.5 cm×1.0 cm to 3.0 cm×2.0 cm. The color Doppler ultrasonography was performed before operation to locate the first dorsal metatarsal artery and its terminal branches, and a first dorsal metatarsal artery terminal branch flap was designed according to the wound condition, with the area of harvested single flap ranged from 1.7 cm×1.2 cm to 3.2 cm×2.2 cm. The wounds in the flap donor areas were transplanted with full-thickness skin grafts from ipsilateral inner calf. The type of flap was recorded, and the diameter of the terminal branch of the first dorsal metatarsal artery was measured during operation. The survival of the flap was observed one week after operation. The wound healing in the flap donor and recipient areas was observed two weeks after operation. At the last follow-up, the functional recovery of the affected fingers was evaluated by the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, the sensory function of the flap was evaluated using the sensory function evaluation standard of British Medical Research Council, the scar in the donor and recipient areas of the flap was evaluated using the Vancouver scar scale (VSS), and the Allen test was conducted in the toe of flap donor area to evaluate the blood flow.Results:The monoblock type flaps in 31 patients and flow-through type flaps in 2 patients were used to repair wounds in single finger, 2 monoblock type flaps in 8 patients were used to repair wounds in 2 fingers at the same time, and the single-pedicle and two-flap type flaps in 3 patients were used to repair wounds in 2 fingers at the same time. The diameter of the fibular terminal branch of the first dorsal metatarsal artery ranged from 0.40 to 1.10 mm, and the diameter of the tibial terminal branch of the first dorsal metatarsal artery ranged from 0.70 to 0.75 mm. All the flaps survived at one week after operation, and all the wounds demonstrated optimal healing in the flap donor and recipient areas at two weeks after operation. All patients were followed up for 6 to 18 months. At the last follow-up, the functional recovery of 48 fingers was evaluated as excellent, and the functional recovery of 7 fingers was evaluated as good; the sensory function of 8 flaps was rated as S2, and the sensory function of 47 flaps was rated as S3, and the two-point discrimination distance of the flaps was 8-14 mm; the VSS scores in the flap recipient areas ranged from 3 to 6, and the VSS scores in the flap donor areas ranged from 4 to 7; the Allen test result of the toes in the donor areas were all negative with normal blood flow.Conclusions:The first dorsal metatarsal artery terminal branch flaps have several advantages, including relatively hidden donor area, shallow anatomical level, simple intraoperative operation, and flexible flap design. The flap is incised without damaging the main artery of the toe, which can repair skin and soft tissue defects of the fingers and ensure the utmost protection of the toes in donor areas. The fingers exhibit improved appearance, texture, sensation, and function after operation.
		                        		
		                        		
		                        		
		                        	
8.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.
		                        		
		                        		
		                        		
		                        	
9.The application of health education with the combination of hospital WeChat platform and teach-back method in improving the quality of life of patients with prostate cancer after operation
Tingting GU ; Huiling WANG ; Yuanyuan SHEN ; Han JIANG ; Ying GU ; Jihui SHI ; Wei FENG
Chinese Journal of Practical Nursing 2024;40(18):1403-1410
		                        		
		                        			
		                        			Objective:To explore the application of 'hospital WeChat' platform combined with feedback method in improving the quality of life of patients with prostate cancer after operation, to provide suggestions for health education of patients with prostate cancer after operation.Methods:A randomized controlled trial was conducted. A total of 80 male patients who underwent radical prostatectomy in the Third People's Hospital of Yancheng City from June 2022 to July 2023 were selected by convenient sampling method. They were divided into control group and experimental group by random number method, with 40 cases in each group. The control group used routine nursing health education, the experimental group used the 'hospital WeChat' platform combined with feedback method for health education. The severity of urinary incontinence, quality of life, and satisfaction with health education after discharge were compared between the two groups.Results:Forty patients in each group completed the study. The age of the control group was (73.40 ± 4.02) years old, and the age of the experimental group was (73.25 ± 4.02) years old. The urinary incontinence scores of the experimental group at 1 week, 1 month and 3 months after discharge were (14.00 ± 1.41), (11.90 ± 1.34) and (5.13 ± 3.45) points, respectively, which were significantly different from those of the control group (16.10 ± 2.04), (15.00 ± 1.20) and (10.90 ± 3.70) points, the differences were statistically significant ( t=-5.36, -10.93, -7.23, all P<0.05). The total scores of quality of life in the experimental group at 1 and 3 months after discharge were (77.51 ± 6.11) and (79.53 ± 5.42) points, which were significantly higher than (67.70 ± 6.62) and (69.05 ± 6.92) points in the control group, the differences were statistically significant ( t=6.89, 7.62, both P<0.05). The satisfaction scores of health education mode, attitude and evaluation items in the experimental group after discharge were (5.03 ± 0.70), (4.95 ± 0.81) and (5.33 ± 0.86) points, respectively, which were higher than those in the control group (3.93 ± 1.00), (3.65 ± 1.10) and (3.80 ± 0.72) points, the differences were statistically significant ( t=5.72, 6.01, 8.59, all P<0.05). Conclusions:The 'hospital WeChat' platform combined with feedback method can effectively improve the urinary incontinence of patients after prostate cancer surgery, and improve the quality of life and satisfaction of health education for patients. This study is hopeful to provide specific measures for health education for clinical prostate cancer patients.
		                        		
		                        		
		                        		
		                        	
10.Therapeutic potential of exosome derived from remote ischemic conditioning in alleviating neurologic dysfunction after cardiac arrest in a rat model
Heng ZHAI ; Jihui WANG ; Xi CHEN ; Yang ZHANG ; Shuqun HU ; Jun WANG ; Yigen PENG ; Ningjun ZHAO ; Xianliang YAN ; Chenglei SU ; Tie XU
Chinese Journal of Emergency Medicine 2024;33(7):991-998
		                        		
		                        			
		                        			Objective:To investigate the therapeutic effect of exosomes derived from remote ischemic conditioning on neurological dysfunction after cardiopulmonary resuscitation in a rat model of cardiac arrest and the relationship with glycocalyx protection.Methods:Exosomes were isolated from the blood of healthy adult male Sprague-Dawley rats using ultracentrifugation after undergoing remote ischemic conditioning for use as intervention drugs. Nanoparticle tracking analysis technology was used for exosome detection. Thirty-six adult male Sprague-Dawley rats were randomly assigned to 3 groups ( n=12 each) :Sham group, Control group and Exosome group. Cardiac arrest was induced by asphyxia for 7 min in the Control and Exosome groups. Placebo or exosomes (1×10 10 Particles) were infused intravenously at 5 min after the rats had returned of spontaneous circulation. Neuropsychological deficit score (NDS), open field test, Y maze and Morris water maze were used to assess neurological outcomes. The levels of plasma Hyaluronic acid (HA) and syndecan-1 (Sdc-1) were detected by Elisa. The expression levels of matrix metalloproteinase-2/9 (MMP-2/9) in hippocampal CA1 region were detected by Western blot. Results:After undergoing remote ischemic conditioning, the plasma levels of exosomes were elevated in rats compared to normal rats. Compared with the control group, the behavioral experiment of rats in the exosomes group were significantly improved, as evidenced by an increase in horizontal locomotor distance (5.86±2.89 vs. 17.53±5.51, P< 0.05), an increase in the correct rate of spontaneous alternation (13.29±15.07 vs. 42.63±10.25, P< 0.05), and a shortening of avoidance latency (25.83±8.54 vs. 13.49±4.55, P< 0.05). Plasma HA and Sdc-1 levels were significantly lower 24 h after resuscitation (HA: 26.34±9.83 vs. 14.84±6.26, P< 0.05; Sdc-1: 0.05±0.03 vs. 0.02±0.02, P<0.05), along with significantly lower MMP-2/9 levels in hippocampal tissue. Conclusions:Exosomes extracted from the plasma of rats undergoing remote ischemic conditioning can improve neurological dysfunction after cardiac arrest in rats, and the mechanism may be related to the inhibition of metalloproteinases and the reduction of endothelial glycocalyx degradation.
		                        		
		                        		
		                        		
		                        	
            
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