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.

Objective:To investigate the value of radiomics signatures based on 18F-FDG PET/CT for predicting molecular classification and Ki-67 expression of breast cancer. Methods:A total of 134 female patients ((55.4±13.3) years) who underwent 18F-FDG PET/CT examination and were diagnosed with breast cancer by pathology in the First Affiliated Hospital of Soochow University from April 2016 to May 2023 were retrospectively enrolled. LIFEx software was used to extract radiomics features and the least absolute shrinkage and selection operator (LASSO) algorithm and independent-sample t test were used to screen potentially meaningful features and calculate the radiomics score, which were considered as radiomics models. Clinical characteristics were selected by supervised logistic regression and clinical models were established. Radiomics features and clinical characteristics were incorporated to logistic regression analysis to establish combined models. ROC curves were drawn and the differences among AUCs were analyzed by Delong test. Results:Among 134 patients, 22 were with triple negative breast cancer (TNBC), 47 were human epidermal growth factor receptor 2 (HER2) over-expression type, 37 were Luminal A type and the rest 28 were Luminal B type. The expression of Ki-67 was high in 85 patients, and was low in the rest 49 patients. The AUCs (95% CI) of the combined models for predicting TNBC, HER2 overexpression type, Luminal A type and Ki-67 expression were 0.843(0.770-0.900), 0.808(0.723-0.876), 0.825(0.711-0.908) and 0.836(0.762-0.894), respectively, which were higher than those of clinical models ( z values: 1.97-3.06, all P<0.05). Conclusion:The predictive model combining radiomics signatures based on 18F-FDG PET/CT and clinical characteristics can well predict the molecular classification and Ki-67 expression level of breast cancer.

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 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.

Objective To observe the impact of semi-solidification enteral nutrition on feeding tolerance,nutritional and infection related indicators,and prognosis in neurocritical patients.Methods Adopting the prospective research method,the neurocritical patients who were admitted to the department of intensive care unit(ICU)of the First Affiliated Hospital of Ningbo University from December 2021 to May 2022 and had to stay in the nasogastric tube for enteral nutrition were selected as the study subjects,pectin was added to achieve the semi-solidification of enteral nutrition,and the patients were divided into pectin group and control group according to the principle of randomized control,with 25 cases in each group.Enteral nutrition was started within 24-48 hours of admission to the ICU in all patients,and pectin plus continuously pumped enteral nutrition preparation was given in the pectin group and continuously pumped enteral nutrition preparation in the control group,all of which was used continuously for more than 7 days.Differences in albumin,prealbumin,Glasgow coma scale(GCS),acute physiology and chronic health evaluation Ⅱ(APACHEⅡ),sequential organ failure assessment(SOFA),procalcitonin(PCT),interleukin-6(IL-6)and C-reactive protein(CRP)were compared between the two groups before and after 7 days of treatment,and enteral nutrition compliance rates at 3 days and 7 days of treatment,as well as the incidence of enteral nutrition intolerance(including vomiting,diarrhea,constipation,aspiration and bloating),along with the length of ICU stay and 28 days prognosis were observed.Results There were no statistically significant differences between the two groups in general clinical data[including gender,age and body mass index(BMI)]and pre-treatment GCS score,APACHEⅡ score,SOFA score,albumin,prealbumin,PCT,IL-6 and CRP levels.The incidence of vomiting,diarrhea,constipation,and bloating during enteral nutrition was significantly lower in the pectin group than those in the control group[vomiting:4.0％(1/25)vs.24.0％(6/25),diarrhea:8.0％(2/25)vs.32.0％(8/25),constipation:20.0％(5/25)vs.65.0％(13/25),bloating:12.0％(3/25)vs.36.0％(9/25),all P<0.05],but the difference in the incidence of aspiration compared with the control group was not statistically significant[4.0％(1/25)vs.16.0％(4/25),P>0.05].Caloric compliance with enteral nutrition was significantly higher in the pectin group than in the control group at both 3 days and 7 days of treatment[3 days of treatment:48.0％(12/25)vs.20.0％(5/25),7 days of treatment:88.0％(22/25)vs.60.0％(15/25),both P<0.05],and the prealbumin level was significantly higher in the pectin group than in the control group at the end of 7 days treatment(mg/L:248.08±43.99 vs.221.64±33.95,P<0.05).There was no statistically significant difference in the comparison of GCS score,APACHEⅡ score,SOFA score,PCT,IL-6,CRP,length of ICU stay,and 28 days mortality between the two groups after treatment.Conclusion The administration of semi-solidification enteral nutrition reduces the incidence of enteral nutrition intolerance,improves caloric intake and nutritional status in neurocritical patients,but has no significant effect on infection indicators and prognosis.

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 application value and treatment effects of multiple free anterolateral perforator flaps of calf for reconstruction of multiple digital wounds in single hand.Methods:From August 2020 to March 2022, 12 patients with soft tissue defects in 35 digits were treated in Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Ten patients were male and 2 were female, aged 25 to 58 years old. Of the patients, 1 had soft tissue defects in 5 digits, 3 in 4 digits, 2 in 3 digits and 6 in 2 digits. The size of defects was from 1.2 cm ×1.2 cm to 7.0 cm×3.5 cm after debridement. The vascular perforators discovered from intraoperative explorations were found originating from the superficial peroneal artery in 24 flaps, from the peroneal artery in 7 flaps and from the anterior tibial artery in 4 flaps. During surgery, the perforator artery and accompanying veins of the flaps were anastomosed with the proper digital artery and palmar or dorsal subcutaneous veins in the recipient site, respectively. The size of the flaps was from 1.5 cm×1.5 cm to 7.5 cm×4.0 cm. No nerve was affected in the surgery. The wound at donor sites in the calf was sutured directly. Regular postoperative follow-ups were conducted at outpatient clinics. The comprehensive evaluation scale of flap was used to assess the conditions of the donor and recipient sites.Results:In this study, all 35 soft tissue defects of digits in 12 patients were reconstructed by the anterolateral perforator flaps of calf. All the 35 flaps survived after surgery, with a 100% of survival rate. The patients were instructed to carry out early functional training after surgery. Follow-up lasted 6 to 24 months, with an average of 11 months. Twenty-five flaps were found in slightly swollen, and further flap thinning surgery were carried out 3 months after the primary surgery, while the rest of the flaps had good appearance and texture. At 6 months after surgery, all flaps recovered a partial deep and shallow sensory and sense of touch. All wound at donor sites in calf had one-stage healing without dysfunction. The comprehensive evaluation scale was excellent in 28 flaps and good in 7 flaps. The excellent and good rate was 100%.Conclusion:It is an effective method to use multiple free anterolateral perforator flaps of calf to reconstruct multiple digit defects in single hand. The flaps can be conveniently harvested and the multiple digital defects in single hand can be reconstructed in primary surgery with small damages to the donor sites and together with satisfactory clinical outcomes.

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.