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.

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.

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.

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.

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

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.

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.

Objective To explore whether the environmental pollutant triclosan(TCS)has negative effects on the various biological characteristics of dental pulp stem cells(DPSCs),as well as the distribution and hazards of TCS in rat dental pulp tissue in vivo,which will provide a basis for the clinical application of DPSCs and the safety of TCS.Methods Tooth collection was approved by the Ethics Committee of Tianyou Hospital Affiliated to Wuhan University of Science and Technology.Human DPSCs were extracted,cultured,and identified.Up to 0.08 mmol/L of TCS was added to the in vitro culture medium of DPSCs.The proliferation ability of DPSCs was detected by CCK-8.The migration ability of DPSCs was detected via scratch assay.The differentiation ability of DPSCs was detected by inducing trilineage differenti-ation.The gene or protein expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),inducible nitric oxide synthase(iNOS),and transforming growth factor-β(TGF-β)in DPSCs were detected.The level of reactive oxygen species(ROS)generated by DPSCs was analyzed using fluorescence staining.Changes in mitochondrial membrane potential of DPSCs were detected using a fluorescent probe.The activity of PI3K/Akt/mTOR,p38,and JNK pathways of DPSCs were detected.Animal experiments were approved by the Animal Ethics Committee of Wuhan University of Science and Technology.A rat model of short-term oral exposure to 50 mg/kg/d of TCS for 2 months was established,and the TCS concentration in the liver,brain,and dental pulp tissues of rats was detected through liquid chromatography-mass spectrometry.Results TCS at 0.02 mmol/L,0.04 mmol/L,and 0.08 mmol/L significantly inhibited the proliferation ability of human-derived DPSCs on the 5th and 7th days of contact.TCS at 0.04 mmol/L and 0.08 mmol/L significantly inhibited the migration ability and tri-lineage differentiation ability of DPSCs on the 3rd day of contact.TCS induced the gene or protein expression of proinflammatory factors including TNF-α,IL-1β,IL-6,and iNOS,induced the gene or protein expression of TGF-β,and inhibited the protein expression of anti-inflammatory factor IL-10.On day 1,TCS at 0.04 mmol/L and 0.08 mmol/L induced the production of ROS in DPSCs and reduced the mitochondrial membrane potential of DPSCs.On day 3,TCS at these levels inhibited PI3K/Akt/mTOR pathway activity and enhanced p38 pathway activity of DPSCs,without affecting the pathway activity of JNK.After short-term intragastric exposure of rats to TCS,TCS was detected in liver(430 ng/mL)and brain(41.4 ng/mL)tissues but not in the dental pulp.The TCS concentration was highest in the liver,but no obvious histopathological changes were observed.Conclusion TCS inhibits a variety of biological characteristics of DPSCs and poses a potential risk to the organism.No TCS exists in the dental pulp tissue of rats exposed to TCS for a brief period of time,and the health of the rats is not damaged.

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.

Pancreatic cancer is one of the most malignant tumors with a 5-year survival rate of 13%. Difficulty in early diagnosis,high tumor heterogeneity,high rate of drug resistance,and lack of effective new drugs are the main reasons for the poor therapeutic effect. Traditional cell line models cannot simulate the tumor environment in vitro and cannot reflect the heterogeneity of pancreatic cancer,while animal models have a long culture process and cannot be used for high-throughput screening. Pancreatic cancer organoids can be continuously expanded and cultured in vitro,which can realistically reflect the heterogeneity of pancreatic cancer and allow high-throughput drug screening,making it an ideal tool for individualized precision diagnosis and treatment of pancreatic cancer. According to recent studies on the evaluation of clinical drug efficacy using pancreatic cancer organoids,the drug sensitivity of pancreatic cancer organoids is highly consistent with the clinical efficacy,demonstrating the feasibility of drug sensitivity of pancreatic cancer organoids in guiding clinical therapy,comfirming the ability to discover potential therapeutic drugs through high-throughput drug screening of pancreatic cancer organoids. At the same time,this review reveals the importance of pancreatic cancer organoids as a model of the pancreatic cancer microenvironment for the development of new drugs and tumor microenvironment research. and the role of pancreatic cancer organoids as a model that can reflect the specific microenvironment of pancreatic cancer for new drug discovery and microenvironmental evaluation. Pancreatic cancer organoids and organ-on-chips are powerful tools for precision companion therapy and new drug discovery.