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 analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites， and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled， and according to the presence or absence of intra-abdominal infection， they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected， and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50， P<0.001）. Compared with the improvement group， the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391， P=0.017） and serum （Z=-2.544， P=0.011）， and compared with the non-infection group， the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420， P<0.001）， while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP）， procalcitonin （PCT）， white blood cell count， and neutrophil-lymphocyte ratio （r=0.288， 0.344， 0.530， 0.510， 0.534， 0.454， 0.330， and 0.404， all P<0.05）. The ROC curve analysis showed that when PCT， CRP， and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection， the AUCs were 0.715 and 0.740， respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038， P=0.043） and serum TREM-1 （OR=1.002， 95%CI： 1.000‍ ‍—‍ ‍1.003， P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection， and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites， and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

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 underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective To evaluate the effect of red-blue light photon assisted therapy on wound healing after flap reconstruction of limb traumatic defects.Methods A total of 146 patients who were admitted to the Ward of Microsurgery of ⅢA hospital of Shanghai from January 2020 to December 2021 and received flap reconstruction surgery for soft tissue defects of limbs were included in this prospective observational study.According to the order of admission,patients were divided into a control group(n=70)and an trial group(n=76).In the control group,a 60W thermal lamp was offered to the patients for locally heating the flaps,with continuous irradiation for 24 hours with a maintaining power of 1-2W,at an approximately 30-45 cm in distance from the flap.In the trial group,based on the thermal irradiation applied to the control group,a combined red and blue light photon irradiation therapy was offered as an additional measure,by twice a day at 20 minutes per session of blue-red light photon irradiation,at 8-12cm in distance from the flap.The two groups were compared in terms of tension of tissues around flap,incidence of infection within 7 days after surgery and the survival of flap within 2 weeks after surgery.Results The two groups showed no significant difference in terms of tissue tension between the 1st and 3rd day after surgery(P<0.05),but with significant differences on the 5th and 7th day after surgery(P>0.05).The trial group exhibited significantly lower incidence of infection within 7 days after surgery compared to that of the control group(P<0.05),and with a significantly higher flap survival rate at 2 weeks after surgery(P<0.05).Conclusion After the flap reconstruction of soft tissue defects of limbs,a red-blue light assisted photon irradiation therapy can effectively improve postoperative tissue tension around a flap,reduce infection rate and improve the survival rate of a flap.It provides an effective and safe interventional measures for postoperative care of the transferred flap.

Objective:To explore the causal relationship between gut microbiota and lung function (FEV1/FVC) using two-sample Mendelian randomization method; To explore its application in the TCM field.Methods:This was a Mendelian randomization study. The GWAS data of gut microbiota from the MiBioGen consortium study and the GWAS data of lung function (FEV1/FVC) published by IEU OpenGWAS in the public database were used, and instrumental variables were extracted according to prespecified thresholds. The inverse variance weighted method (IVW) was mainly used for analysis. The results were evaluated according to the effect indicator β value and 95% CI. When the IVW method was statistically significant, further sensitivity analysis was performed. Leave-one-out test, heterogeneity test, horizontal gene pleiotropy test and MR-Egger regression intercept analysis were used to verify the stability and reliability of the results. Results:A total of 10 causal relationships between gut microbiota and lung function (FEV1/FVC) were determined using the IVW method: family. BacteroidalesS24.7group ( β=-0.029, P=0.015), family. ClostridialesvadinBB60group ( β=-0.028, P=0.040), family. Streptococcaceae ( β=-0.056, P=0.042), genus. LachnospiraceaeFCS020group ( β=0.025, P=0.029), genus. Lactococcus ( β=-0.024, P=0.038), genus. Peptococcus ( β=0.025, P=0.049), genus. RuminococcaceaeUCG011 ( β=-0.030, P=0.038), genus. Ruminococcus2 ( β=0.028, P=0.033), genus. Terrisporobacter ( β=-0.030, P=0.018), phylum. Cyanobacteria ( β=0.027, P=0.039). Leave-one-out analysis showed that the results were stable, and the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation could be removed. Conclusion:The gut microbiota may play a role in the changes of lung function, which to a certain extent confirms the TCM theory of "exterior-interior relationship between the lung and large intestine", and can provide certain reference for the research direction of TCM.

Objective:To explore the predictive value of preoperative pelvic floor electromyography(EMG)parameters for the risk of urinary incontinence after prostate cancer surgery.Methods:This study retrospectively analyzed the medical records of 271 patients who underwent radical prostatectomy in the urology department of Peking University First Hospital from January 2020 to October 2022.The data included patient age,body mass index(BMI),international prostate symptom score(IPSS),prostate-specific antigen(PSA)levels,Gleason score,type of surgery,urethral reconstruction,lymph node dis-section,nerve preservation,catheterization duration,D'Amico risk classification,American Society of Anesthesiologists(ASA)score,Charlson comorbidity index,postoperative duration,prostate volume,and pelvic floor EMG parameters(pre-resting mean,fast muscle mean,and slow muscle mean scores).Independent risk factors affecting early postoperative urinary incontinence were identified through multiva-riate Logistic regression analysis.The predictive efficacy of pelvic floor EMG results was evaluated by cal-culating the area under the receiver operating characteristic(ROC)curve,and the optimal threshold for early postoperative urinary incontinence was determined based on the Youden index and clinical signifi-cance.Results:The study included 271 prostate cancer patients,with an 81.9％rate of voluntary urinary control post-surgery.The median score for fast pelvic floor muscles was 23.5(18.2,31.6),and for slow muscles,it was 12.5(9.6,17.3).Among the patients,179(66.1％)did not preserve nerves,and 110(40.6％)underwent urethral reconstruction.Advanced age and low fast muscle scores were identified as independent risk factors for urinary incontinence.Patients aged ≤60 had 5.482 times the voluntary urinary control rate compared with those aged ≥70(95％CI:1.532-19.617,P＜0.05).There was a significant correlation between fast muscle scores and urinary incontinence recovery(OR=1.209,95％CI:1.132-1.291,P＜0.05).When the optimal threshold for preoperative fast muscle score was set at 18.5,the ROC sensitivity and specificity were 80.6％and 61.2％,respectively.Con-clusion:Preoperative pelvic floor EMG parameters show good predictive accuracy and clinical applicabili-ty for the risk of urinary incontinence after prostate cancer surgery.These parameters can be used for ear-ly identification of urinary incontinence risk,with age and fast muscle scores being important predictors.

OBJECTIVE To retrospectively summarize the CT and enhanced MRI imaging characteristics of common unilateral benign nasal and sinus lesions and to outline key points for differentiation from malignant lesions.METHODS A total of 134 cases of unilateral benign nasal and sinus lesions were included in this study,with preoperative sinus CT and enhanced MRI examinations performed.The imaging characteristics of CT and MRI,the extent of the lesions,and the involvement and destruction of surrounding bone and structures were recorded and summarized for each type of lesion.RESULTS Unilateral lesions on CT appeared as generally homogeneous soft tissue density shadows.The affected sinus bones showed internal calcification,localized bone hyperplasia of the sinus wall,extensive uniform centripetal bone hyperplasia and thickening of the sinus wall,expansive destruction of the sinus wall bone,and worm-eaten destruction of the sinus wall bone in 33,13,29,9,and 5 cases,respectively.On MRI T1WI,the lesions appeared as generally homogeneous isointense shadows.Enhanced T1 images showed mild,moderate,and significant enhancement in 3,10,and 108 cases,respectively,with 55 cases presenting as mixed signals.CONCLUSION The imaging manifestations of unilateral benign lesions vary.CT can clearly present high-density shadows such as calcifications within unilateral lesions and changes in surrounding bone.Enhanced MRI of the sinuses provides richer information about the different components within the lesions.Careful differentiation of unilateral lesions should be performed by combining the imaging characteristics of sinus CT and enhanced MRI.

Wilson's disease, also known as hepatolenticular degeneration, is an inherited disorder of copper metabolism caused by homozygous or compound heterozygous variants in the ATP7B gene, which is mainly clinically manifested as liver disease and/or neurological/psychological disorders, and Kayser-Fleischer ring in the peripheral cornea. Patients with Wilson's disease are currently treated with lifelong use of chelating agents that promote copper ion excretion and/or zinc agents that reduce copper absorption, but there is still an unmet clinical need because some patients who receive treatment have poor efficacy, disease progression, or serious adverse drug reactions. In recent years, new therapeutic drugs have been developed rapidly. This article will summarize the advances in drug treatment of Wilson's disease, shedding new light on the treatment of Wilson's disease.