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.

Objective:To explore the clinical effects of free bilateral turbocharged anterolateral thigh flaps in tandem in repairing extensive wounds in the foot and ankle.Methods:The study was a retrospective observational study. From April 2020 to June 2023, 12 patients with extensive wounds in the foot and ankle who met the inclusion criteria were admitted to the Department of Wound Repair Surgery of Suzhou Ruihua Orthopedic Hospital, including 8 males and 4 females, aged 21 to 65 years. The wound area after debridement ranged from 27 cm×14 cm to 37 cm×20 cm. The bilateral perforator flaps pedicled with either oblique or descending branches of the lateral circumflex femoral artery were designed and harvested based on the size and shape of the wounds. The individual flap incision area ranged from 16 cm×9 cm to 34 cm×12 cm. The non-homologous perforator of the flap on the one side was turbocharged by anastomosing it with the gross muscular branch or main vessel of the oblique or descending branch of the lateral circumflex femoral artery from the flap. Subsequently, the proximal end of the oblique or descending branch of the lateral circumflex femoral artery and its accompanying vein from the flap on the one side were connected end-to-end with either the anterior tibial artery and vein, posterior tibial artery and vein, or dorsal foot artery and vein in the recipient area, the distal end of the oblique or descending branch of the lateral circumflex femoral artery and its accompanying vein from the flap on the one side were anastomosed end-to-end with a source vessel originating from flap on the other side. The wounds in the flap donor areas were sutured directly. The number and source of perforators carried by the flaps and the duration of the flap repair surgery were recorded. The survival of the flap, the occurrence of vascular crisis, and the wound healing at both donor and recipient areas were observed after surgery. The flap condition, appearance and function of the affected limb were observed during follow-up. At the last follow-up, the sensory function of the flap was assessed using the British Medical Research Council's sensory rating standard, the foot and ankle function of the affected limb was evaluated according to the American Orthopedic Foot and Ankle Society scoring standard.Results:A total 24 flaps were successfully harvested, carrying 60 perforators, including 34 perforators from the oblique branch of the lateral circumflex femoral artery, 24 perforators from the descending branch of the lateral circumflex femoral artery, one perforator from the transverse branch of the lateral circumflex femoral artery, and one perforator from the direct branch of the femoral artery. The duration of the flap repair surgery ranged from 4.2 to 9.0 hours. The flaps of 12 patients exhibited complete survival after surgery. A total of two flaps of two patients experienced venous crisis after surgery but survived through emergency exploration. One patient encountered undesirable wound healing at the donor area of flap on the one side after surgery, which healed after dressing change, debridement, and suturing. The remaining patients' donor area wounds healed. Two patients displayed impaired wound healing in the recipient area, which improved after dressing change and resection of residual sequestrum, and the wounds in the recipient area of other patients healed successfully. During the follow-up of 4-26 months, the flaps demonstrated favorable color and texture, slight edematous appearance, and partial sensory recovery, as well as good aesthetic and functional restoration of the affected limbs. At the last follow-up, the sensory function of the flap was assessed as grade S2 in 9 cases and grade S3 in 3 cases; the foot and ankle function of the affected limb was evaluated as excellent in two cases, good in 9 cases, and fair in one case.Conclusions:The bilateral turbocharged anterolateral thigh flaps have numerous sources of perforators. By implementing supercharging of non-homologous perforators within the flap, the vascular supply to the flap is turbocharged, thereby mitigating the risk of extensive flap necrosis. The flap is an effective approach for repairing extensive wounds in the foot and ankle, resulting in improved function of the affected limb after repair.

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.

Seven novel acylphloroglucinol-sesquiterpenoid adducts, designated as dryatraols J-P (1-7), were isolated from the rhizomes of Dryopteris atrata (Wall. ex Kunze) Ching. The structures, including absolute configurations, were elucidated using comprehensive spectroscopic data, calculated ¹³C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus (¹³C NMR-DP4+) probability analysis, and ECD calculations. These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties. Notably, compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane- or rulepidanol-type sesquiterpene, while compound 7 features a hydroxylated monomeric acylphloroglucinol motif. A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus (RSV) with IC₅₀ values ranging from 0.75 to 3.12 μmol·L^-1 compared to the positive control (ribavirin).
Antiviral Agents/isolation & purification* ; Phloroglucinol/isolation & purification* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Dryopteris/chemistry* ; Respiratory Syncytial Viruses/drug effects* ; Humans ; Rhizome/chemistry* ; Drugs, Chinese Herbal/pharmacology*

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Objective:To investigate the clinical effect of reconstruction of the degloving injury of thumb and finger with free perforator flap of superficial peroneal artery.Methods:This is a retrospective study. From June 2020 to June 2023, 18 superficial peroneal artery perforator flaps from 14 calves were used to treat 15 degloved digital wounds of 14 patients in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. There were 13 single digital degloving wounds and 1 two-digital degloving wounds. Of which, 3 digits were reconstructed with 2 free perforator flaps of ipsilateral superficial peroneal artery and 12 with a single free perforator flap of superficial peroneal artery. The size of wounds was 4.0 cm×2.0 cm-10.0 cm×4.0 cm, and the flaps were 5.0 cm×3.0 cm-12.0 cm×4.0 cm in size. The donor sites in calves were sutured layer by layer with absorptive sutures. Postoperative follow-ups were conducted through regular outpatient visits, phone calls or WeChat. Survival of flaps, postoperative complications, therapeutic effect of the flaps and patient satisfaction were observed.Results:There was no vascular compromise or wound infection of the flaps. All patients were included in the 4 to 36 months of postoperative follow-up, with an average of 9.86 months. All flaps had good appearance, without obvious swelling. Colour and texture of the flaps was close to the surrounding skin. The flaps had no obvious pigmentation or ulcer and scar hyperplasia at recipient site. Sensation of the flaps recovered to S 2 to S 3. There was no obvious scar hyperplasia, pain or dysfunction at donor sites. According to the comprehensive evaluation scale of flap, the scores were found at 81 to 91, with an average score of 85 in the 14 patients, and of whom 2 were excellent and 12 were good. Patient satisfaction was evaluated according to the Michigan Hand Outcomes Questionnaire (MHQ) and 10 patients were very satisfied and 4 were satisfied. Conclusion:Free perforator flap of superficial peroneal artery is one of the ideal flaps in reconstruction of degloving injury of thumb and fingers. It features constant and multiple perforators, reliable blood supply, high survival rate, flexible in design, thin and a small damage to the donor site.

Hand degloving injury represents one of the most severe forms of hand trauma, characterised by challenging treatment and a complex prognostic outcome. It is crucial to effectively utilise the degloved tissues in emergency or primary repair of a hand degloving injury. This consensus provides a comprehensive review of the existing literature on definition, classification, emergency assessment, debridement, judgment of skin viability, in situ repair of the degloved skin, and adjunctive treatment for degloving injury of hand. Based on conclusion of both domestic and international experiences, this expert consensus on the classification of hand degloving injury and the emergency repair with the avulsed skin is established, aiming to provide a guidance to surgeons on standardised treatment strategy and improve the management of hand degloving injury.

In January 2021, a young male patient was admitted to the Department of Hand Surgery, Suzhou Ruihua Orthopeadic Hospital for a soft tissue degloving defect of distal segment of right thumb caused by machine compression. The thumb defect was reconstructed using a tiled flap with a right hallux nail flap and a lateral flap of left second toe. Donor site of the hallux nail flap was reconstructed by a lateral flap of right second toe, while the donor site of lateral flap of left second toe was covered by a skin graft of abdomen. At 1-year follow-up, the reconstructed nail was found excellent according to the established criteria. Two-point discrimination (TPD) was measured at 5 mm, and the affected thumb exhibited satisfactory flexion and extension and functions of thumb-to-palm and thumb-to-fingers oppositions. Donor sites in both feet achieved favorable appearance and function, with a Maryland foot score of 96. Only a linear scar was in abdominal donor site.

Objective:To investigate and compare the clinical effect of anterolateral thigh perforator flap (ALTPF) with a pedicle of the oblique branch and a pedicle of the descending branch of lateral circumflex femoral artery in treatment of wounds in limbs.Methods:From December 2020 to December 2021, a retrospective analysis was performed on 53 patients who received reconstruction of wound with free ALTPF. Patients were divided into a group of ALTPF with oblique branch of lateral circumflex femoral artery (oblique branch group) and a group of ALTPF with descending branch of lateral circumflex femoral artery (descending branch group) according to the vascular pedicle. Of the blique branch group ( n=28): 12 patients had the wound in wrist, 3 in forearm, 7 in ankle and foot, and 6 in calf. The time for ALTPF reconstructive surgery after admission ranged from 0 to 25 days, with an average of 15.3 days. Among the patients, 6 received emergency treatment. The size of soft tissue defect was 5.0 cm×8.0 cm-21.0 cm×10.0 cm, and the size of flap was 6.0 cm×8.5 cm-22.0 cm×10.0 cm. Of the descending branch group ( n=25): 7 patients had the wound in wrist, 3 in forearm, 2 in upper arm, 10 in ankle and foot, and 3 in calf. The time for ALTPF reconstructive surgery after admission ranged from 0 to 22 days, with an average of 14.7 days. Among the patients, 4 received emergency treatment. The size of soft tissue defect was 12.0 cm×4.0 cm-28.0 cm×10.0 cm, and the size of flap was 13.0 cm×5.0 cm-28.0 cm×10.0 cm. The donor sites were directly sutured in layers after the surgery. The number of perforating branches in anterolateral thigh was detected by high-frequency CDU and recorded before surgery. The number, calibre, type of perforating branches observed during surgery and the size of flaps, length of the vascular pedicles of the flaps and the time for flap harvesting were recorded. Postoperative follow-up was conducted through outpatient visits, WeChat and other means. The survival of the flap, the healing of the donor site and complications were observed. The outcomes of flap reconstructive surgery were evaluated by the comprehensive score scale during follow-up. The data were analyzed using SPSS 22.0 statistical software. P<0.05 was considered statistically significant. Results:There is no significant difference in general information between the 2 groups ( P>0.05). In the oblique branch group, the length of vascular pedicle of the flaps was 5.0-15.0 (9.89±2.66) cm, the ratio of intermuscular perforator was 56.52%(26/46), and the inner diameter of perforators was 0.3-1.1 (0.67±0.20) mm and the time for flap harvesting was 22.5 (6.0-75.0) minutes. In the descending branch group, the length of vascular pedicle of the flaps was 7.0-16.0 (11.52±2.67) cm, the proportion of intermuscular perforator was 34.69%(17/49), the inner diameter of perforators of the flap was 0.3-1.2(0.70±0.23) mm and the time for flap harvesting was 35.0 (9.0-78.0) minutes. In comparison with the 2 groups, it was found that the oblique branch group had a shorter length of vascular pedicle, a higher proportion of intermuscular perforating branches and a shorter time in flap harvesting. The difference was statistically significant ( P<0.05). No statistically significant was found in the number and inner diameter of the perforating branches between the 2 groups ( P>0.05). Altogether, 51 flaps in the 2 groups survived. One flap in each group had partial necrosis at the distal end of flap, with the necrotic sizes of 5.0 cm×5.0 cm and 5.0 cm×4.0 cm, respectively, and they healed after skin grafting without obvious vascular. The survival rates of the 2 groups of flaps were 96.43% and 96.00%, respectively. The postoperative follow-up lasted for 6-18 months, with an average of 12 months. The appearance of the flaps in 10 patients was slightly bloated, and flap thinning and plastic surgery were carried out at 4-6 months after the primary flap surgery. Else, all the flaps regained protective sensation, all the donor sites and recipient sites healed well, and the donor sites of the thigh was good without pain, numbness or other discomfort. Comprehensive evaluations of the flaps were conducted at the final follow-up with the comprehensive evaluation scale for flaps. The scores of 28 patients in the oblique branch group achieved 73-98 with an average of 86.3. Twelve patients had the scores in comprehensive evaluation of excellent, 14 of good, and 2 of fair, with the excellent and good rate of 92.86%(26/28). The scores of 25 patients in the descending branch group ranged from 72-97 with an average of 85.8, of which 11 patients had the scores of comprehensive evaluation in excellent, 12 in good and 2 in fair, with the excellent and good rate of 92.00% (23/25). There was no statistically significant difference in the survival rate and comprehensive evaluation scales between the 2 groups of flaps ( P>0.05). Conclusion:ALTPF pedicled with oblique branch of lateral circumflex femoral artery has a higher number of perforating branch, a shorter harvesting time and less damage to the donor site than those of the ALTPF pedicled with descending branch of lateral circumflex femoral artery. When both oblique and descending branches of lateral circumflex femoral artery are present or with the absence of a descending perforating branch, the oblique branch of lateral circumflex femoral artery is the preferred perforating vessel for pedicle in harvesting of an ALTPF.