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 In this study,2,4-dinitrochlorobenzene(DNCB)was used to induce the establishment of an atopic dermatitis(AD)model in BALB/c homozygous mice to simulate the skin inflammatory complications in patients with clinical malignancies.Methods BALB/c mice were divided into different groups:negative control group(NC group),model group(MODEL group),atopic dermatitis group(AD group),and dexamethasone group(DEX group).After the mice in MODEL group and DEX group were inoculated with S-180 tumor cells in the axilla,MODEL group,AD group and DEX group were stimulated with DNCB on the dorsal skin and the ear to establish an animal model of atopic dermatitis in tumor-bearing mice.Changes in body weight were observed and recorded,the dorsal skin condition of mice was assessed after the last administration of the drug,the spleen was taken to calculate the spleen coefficient,the difference in the mass of mouse ear slices was determined to calculate the degree of auricular swelling and the rate of inhibition of swelling,and histopathological tests were performed on the dorsal skin tissues to detect the levels of IgE,TNF-α,IL-4,and IL-17 in the serum using an ELISA assay.Results Compared with the NC group,the skin of mice in the MODEL and AD groups showed erythematous,papular,scaly and mossy changes,accompanied by weight loss,and a significant increase in splenic coefficient and auricular swelling.Pathologic findings showed an incomplete skin structure,a significant increase in skin thickness,a large infiltration of inflammatory cells,and an increase in the number of mast cells.Serum levels of IgE,TNF-α,IL-4 and IL-17 were increased.Compared with the MODEL group,the DEX group showed an improvement in all the assays.Conclusions DNCB excitation can successfully establish an animal model of AD in hormonal mice,which is drug-controllable,which provides a useful scientific tool for conducting scientific research related to malignant tumors and skin inflammation.

A 34-year-old female patient with multiple injuries in a car accident was admitted to hospital and received inosine injection.After 11 days,leukemioid reaction mainly characterized by"abnormal increase in white blood cell count"occurred,and the white blood cell count reached up to 38.26×109·L-1.Considering that inosine injection was the cause,the white blood cell count gradually decreased to 15.84×109·L-1 after the drug was stopped.Naranjo's assessment scale was used to evaluate the association of adverse reactions,with a score of 6,and the result was"very likely to be relevant".The cases reported in this paper belong to new adverse reactions caused by inosine injection,suggesting that inosine injection as an adjunct should pay attention to drug safety.If there is an abnormal increase in white blood cell count,it is necessary to be alert to the possibility of"leukemioid reaction"and stop the drug in time if necessary.

Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

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 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.Methods A 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).Results The 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.Conclusion The 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.

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.

Objective To develop and validate a risk prediction model for infiltration/extravasation in peripheral intravenous catheter therapy.Methods This retrospective study analyzed 942 patients who completed the Infiltration/Extravasation Risk Assessment Form between January and June 2023 at the First Affiliated Hospital of Army Medical University(including Departments of Neurology,Endocrinology,Gastroenterology and Hepatobiliary Surgery).Patients were allocated to a derivation cohort(n=628)and validation cohort(n=314)in a 2∶1 ratio based on catheterization chronology.The derivation cohort served for model development and internal validation,while the validation cohort underwent external validation.Logistic scoring method constructed the risk model,with Hosmer-Lemeshow(HL)test assessing goodness-of-fit and ROC curve evaluating predictive performance.Twenty-one potential risk factors were assessed,including age,gender,chronic diseases,clinician experience,treatment compliance,and total infusion volume.Results Infiltration/extravasation occurred in 48 cases(5.10%incidence:31 derivation/17 validation).Among 21 factors,15 showed significant association(P<0.05),with 6 independent predictors:junior high school education or below(OR=5.2),chronic disease history(OR=3.1),poor compliance(OR=2.8),lower extremity venipuncture(OR=4.1),total infusion≥1 000 mL(OR=3.5),and hyperosmotic/corrosive medications(OR=6.7).The final prediction model was:Y=2×(low education)+1×(chronic disease)+1×(poor compliance)+1×(lower extremity puncture)+1×(volume≥1 000 mL)+2×(corrosive agents).For the derivation cohort,AUC was 0.967(95%CI:0.936～0.998),specificity 0.911,sensitivity 0.935,with good calibration(χ2=4.135,P=0.845).Validation cohort showed AUC 0.939(0.853～1.000),specificity 0.919,sensitivity 0.941,and acceptable calibration(χ2=8.998,P=0.085).Conclusion This model demonstrates excellent discriminative ability and calibration,providing an effective tool for identifying high-risk patients and guiding targeted preventive strategies.