Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

Objective To investigate the organ protective role and the underlying mechanism of nafamostat mesylate(NM)in a renal ischemia-reperfusion injury(RIRI)model.Methods A total of 21 healthy male Sprague-Dawley(SD)rats were randomly assigned to 3 groups(n=7 in each group),including the sham operation group(Sham group),the RIRI group,and the NM intervention group(NM group).The RIRI and NM groups underwent ischemia-reperfusion injury(IRI)modeling.The NM group was given an intraperitoneal injection of NM at 0.75 mg/kg before modeling.Venous blood and renal tissue samples were then collected from the rats 24 hours after modeling.The levels of serum creatinine,cystatin C,and serum inflammatory factors were determined using the serum samples.Hematoxylin-eosin(HE)staining and TUNEL stainings were performed on the renal tissues to evaluate the damage of the renal tissues.The localization and expression of HMGB1 were analyzed by immunofluorescence and Western blotting,respectively.Single-cell RNA sequencing of the nuclei was performed to obtain the single-cell transcriptome of the kidneys from the rats in the RIRI and the NM groups and to acquire the RIRI cell profile.The cells were annotated according to the cell marker genes to explore the cell type composition in the disease model and the functional status of immune cells between the groups.Results 1)Compared with those of the Sham group,the levels of cystatin C,creatinine,and inflammatory factors in the RIRI and NM groups were significantly increased,and the expression levels in the NM group were lower than those in the RIRI group(P＜0.05).Compared with those of the RIRI group,the tubular injury score and apoptosis rate in the NM group were significantly decreased(P＜0.05),but those of both the NM and RIRI groups were higher than those of the sham group.Compared with that in the RIRI group,the expression of HMGB1 in the NM group was significantly decreased(P＜0.05),but the expression levels in both the RIRI and NM groups were higher than that in the sham group.Immunofluorescence showed that there was increased cytoplasmic expression of HMGB1 in both the NM and RIRI groups,with the increase being more prominent in the RIRI group.2)A total of 13 major cell populations were identified through the single-nucleus sequencing results.The proportion of tubular cells in the NM group was higher,with the HMGB1 gene being highly expressed in the damaged proximal convoluted tubular cells.The proportion of the polarized Macro3 cell subpopulation in the macrophages in the NM group was lower compared to that in the RIRI group.Conclusion NM may play a protective role in a rat model of RIRI,and its underlying mechanisms may be related to the regulation of the functional abnormalities of HMGB1-mediated macrophages.

Objective To investigate the therapeutic effect and potential mechanisms of allogeneic renal subcapsular transplantation of CD24+renal epithelial cells for the treatment of acute kidney injury(AKI)induced by ischemia-reperfusion(I/R).Methods CD24+renal epithelial cells were isolated from mouse kidneys using flow cytometric sorting and expanded by passaging.C57BL/6N mice were randomly divided into three groups:the normal control group(n=8,sham surgery only),the model control group(n=8,unilateral kidney I/R plus contralateral nephrectomy),and the CD24+cell treatment group(n=8,AKI model followed by renal subcapsular transplantation of CD24+cells).Mice were euthanized at 24 h after modeling and serum was collected to measure biochemical markers[serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)].Renal tissues were subjected to pathological evaluation and macrophage staining.An M1-polarized macrophage model was established using mouse bone marrow-derived macrophages co-cultured with CD24+renal epithelial cells.The polarization state of macrophages was assessed by quantitative real-time polymerase chain reaction(qPCR)and flow cytometry.Results CD24+renal epithelial cells were successfully isolated and passaged stably.Compared with the normal control group,the model control group exhibited significantly elevated Scr and BUN levels and renal pathological damage.In contrast,the CD24+cell treatment group showed significant reduction in serum biochemical markers and pathological injury compared with the model control group,along with reduction in M1 macrophage infiltration in the kidneys(P<0.05,P<0.01).In vitro co-culture experiments demonstrated that in the CD24+co-culture group,the expression of M1 polarization-related markers in macrophages was significantly lower than that in the non-co-culture group,and the proportion of CD80+M1 macrophages in the co-culture group decreased(P<0.05,P<0.01).Conclusion Allogeneic renal subcapsular transplantation of CD24+renal epithelial cells can alleviate I/R-induced AKI by inhibiting M1 macrophage polarization through paracrine mechanisms.

Objective To investigate the therapeutic effect and potential mechanisms of allogeneic renal subcapsular transplantation of CD24+renal epithelial cells for the treatment of acute kidney injury(AKI)induced by ischemia-reperfusion(I/R).Methods CD24+renal epithelial cells were isolated from mouse kidneys using flow cytometric sorting and expanded by passaging.C57BL/6N mice were randomly divided into three groups:the normal control group(n=8,sham surgery only),the model control group(n=8,unilateral kidney I/R plus contralateral nephrectomy),and the CD24+cell treatment group(n=8,AKI model followed by renal subcapsular transplantation of CD24+cells).Mice were euthanized at 24 h after modeling and serum was collected to measure biochemical markers[serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)].Renal tissues were subjected to pathological evaluation and macrophage staining.An M1-polarized macrophage model was established using mouse bone marrow-derived macrophages co-cultured with CD24+renal epithelial cells.The polarization state of macrophages was assessed by quantitative real-time polymerase chain reaction(qPCR)and flow cytometry.Results CD24+renal epithelial cells were successfully isolated and passaged stably.Compared with the normal control group,the model control group exhibited significantly elevated Scr and BUN levels and renal pathological damage.In contrast,the CD24+cell treatment group showed significant reduction in serum biochemical markers and pathological injury compared with the model control group,along with reduction in M1 macrophage infiltration in the kidneys(P<0.05,P<0.01).In vitro co-culture experiments demonstrated that in the CD24+co-culture group,the expression of M1 polarization-related markers in macrophages was significantly lower than that in the non-co-culture group,and the proportion of CD80+M1 macrophages in the co-culture group decreased(P<0.05,P<0.01).Conclusion Allogeneic renal subcapsular transplantation of CD24+renal epithelial cells can alleviate I/R-induced AKI by inhibiting M1 macrophage polarization through paracrine mechanisms.

Objective To investigate the relationship between platelet/hemoglobin ratio(PHR)and the severity of diabetic foot ulcer(DFU)and its predictive value for DFU progression.Methods A retrospective study was performed in 345 DFU patients treated in Department of Endocrinology,the First Affiliated Hospital of Army Medical University from March 2018 to March 2023.Their general demographic information was obtained,and the results of laboratory tests,including hemoglobin Alc(HbA1c),fasting plasma glucose(FPG),biochemical and related blood routine indicators were collected.According to Wanger grading,the patients were assigned into mild(n=145)and severe ulcer groups(n=200).The demographic data and clinical parameters were compared between the 2 groups.Multivariate logistic regression model was applied to identify the independent predictors for severe ulcer in DFU,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive performance of PHR for DFU progression.Results The severe ulcer group presented remarkable increases in male proportion,HbA1c and FPG levels,platelet(PLT)count and PHR when compared with the mild ulcer group(P＜0.05).Multivariate logistic regression analysis revealed that PHR and male were independent risk factors,while,HDL-C was a protective factor for progression to severe ulcer in DFU patients(P＜0.05).ROC curve analysis showed that the area under the curve of PHR for predicting severe ulcer was 0.701(95％CI:0.646～0.756).Conclusion PHR is strongly associated with the severity of DFU,and shows certain predictive value for the progression to severe ulcer in DFU patients.

[Objective] To investigate the pathological characteristics of false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT based on the pathology of whole mount specimens, in order to more accurately assess the degree of malignancy within the prostate tissue and avoid overdiagnosis and unnecessary treatment. [Methods] A total of 77 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT before radical prostatectomy in Nanjing Drum Tower Hospital during Jan.2018 and Dec.2022 were retrospectively analyzed.The pathology of whole mount specimens was detected.Two nuclear physicians examined all imaging plates without knowing the pathological results.Two pathological physicians completed all pathological diagnosis without knowing the imaging results.The pathological characteristics of false-positive lesions were determined by matching ⁶⁸Ga-PSMA-11 PET/CT and pathological specimens.To analyze the pathological features of false-positive lesions, true-negative lesions were randomly delineated and defined.The pathological features of false-positive and true-negative lesions were analyzed and compared using Fisher exact test. [Results] After the imaging and pathological sections were matched, 21(16.3%) false-positive lesions were identified.The pathological characteristics of the 21 false-positive lesions were as follows: 16 (76.2%) simple atrophy with cyst formation, 3(14.3%) prostatic nodular hyperplasia, and 2(9.5%) inflammation.The pathological characteristics of 21 true-negative lesions were: 13(61.9%) normal glands, 5(23.8%) prostatic nodular hyperplasia and 3(14.3%) simple atrophy with cyst formation.Fisher exact test showed that the proportion of simple atrophy with cyst formation in the pathological features of false-positive lesions and true-negative lesions was statistically significant (76.2% vs.14.3%, P<0.001). [Conclusion] Simple atrophy with cyst formation may be a characteristic pathological type of the false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT.

Objective To investigate the clinical diagnostic value of extra-spindle pole-like protein 1(ESPL1)in the progression of hepatitis B virus(HBV)-related liver fibrosis.Methods A total of 228 patients with HBV infection who were admitted to The First Affiliated Hospital of Guangxi Medical University from June 2017 to August 2023 were enrolled.The transient elastography system FibroScan was used to determine liver stiffness measurement(LSM)for all patients,and according to the LSM value,they were divided into non-liver fibrosis group with 80 patients,mild liver fibrosis group with 83 patients,advanced liver fibrosis group with 30 patients,and liver cirrhosis group with 35 patients.ELISA was used to measure the serum level of ESPL1.The Kruskal-Wallis H test was used for comparison of the serum level of ESPL1 between the four groups;the Spearman correlation analysis was used to investigate the correlation between ESPL1 and LSM;the receiver operating characteristic(ROC)curve was used to analyze the value of serum ESPL1 in predicting the progression of liver fibrosis.Results The liver cirrhosis group had a significantly higher serum level of ESPL1 than the non-liver fibrosis group and the mild liver fibrosis group(both P<0.05),and the advanced liver fibrosis group and the mild liver fibrosis group had a significantly higher serum level of ESPL1 than the non-liver fibrosis group(both P<0.05).The correlation analysis showed that there was a positive correlation between serum ESPL1 and LSM in the patients with HBV infection and varying degrees of liver fibrosis(r=0.515,P<0.001).Serum ESPL1 had an area under the ROC curve(AUC)of 0.809 in predicting liver cirrhosis and an AUC of 0.638 in predicting advanced liver fibrosis,with a sensitivity of 87.5%and 100%,respectively,and a specificity of 59.7%and 31.3%,respectively.Conclusion There is a certain correlation between serum ESPL1 and HBV-related liver fibrosis,and higher serum ESPL1 may indicate a higher degree of liver fibrosis.Serum ESPL1 is expected to become one of the serum markers for assisting in the diagnosis of liver cirrhosis and an important clinical method for dynamically monitoring the progression of liver fibrosis in patients with HBV infection.

Objective To compare the survival outcomes of bladder cancer with non-pure urothelium(BCa with n-pU)and bladder cancer with pure urothelium(BCa with pU)treated with robot-assisted radical cystectomy(RARC).Methods Clinical data of BCa patients treated with RARC in Nanjing Drum Tower Hospital during Oct.2014 and Mar.2022 were retrospectively analyzed.The patients were divided into n-pU group and pU group.After the baseline differences between groups were balanced with propensity score matching(PSM),the overall survival(OS)and recurrence-free survival(RFS)curve were plotted using Kaplan-Meier method and compared using Log-rank test.Univariate and multivariate analysis were performed with Cox model to identify the influencing factors of prognosis.Based on the results,a secondary grouping was performed to compare the survival differences between subgroups and further investigate the prognostic factors.Results After PSM,there were 53 pairs of BCa patients.There were no significant differences in the baseline data between the pU and n-pU groups(P＜0.05).Regardless of T stage,there were no significant differences in OS and RFS between the two groups(P=0.217,P=0.109).Univariate Cox regression analysis showed that T stage(＞T2)was a significant risk factor of OS and RFS(P＜0.05).In the early pathological stage(≤T2),there were no significant differences in OS and RFS(P=0.565,P=0.344).In the advanced pathological stage(＞T2),the OS and RFS of n-pU were significantly worse than those of pU patients(P=0.025,P=0.034).Conclusion The prognosis of BCa patients with n-pU who received RARC is significantly correlated with pathological status.At＞T2 stage,n-pU patients have worse prognosis than pU patients in the same pathological status.

OBJECTIVE To study the pharmacodynamics and pharmacokinetics of semaglutide(Sem)capsules in type 2 diabetic model rats.METHODS Male SD rats were divided into the normal control group,type 2 diabetic model group and model+Sem capsules(0.839,1.678 and 2.517 mg·kg-1)groups.A type 2 diabetic rat model was induced by high sugar and high fat diet feeding combined with ip given streptozotocin(STZ)injection.Seven days after modeling,the model+Sem capsules group was ig given Sem capsules at the corresponding dose in a fasting state,once a day,for 14 d.Body mass,fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)levels were regularly mea-sured in each group of rats.Plasma from rats in the model+Sem capsules 0.839,1.678 and 2.517 mg·kg-1 groups at different time points was collected at the end of the continuous administration of Sem capsules,and the content of Sem in the plasma of rats was determined by liquid chromatography-tandem mass spectrometry.Concentration-time curves were plotted,and the main pharmacokinetic parameters were fitted by the WinNonlin non-atrial model method.RESULTS Compared with the model group,the body mass of rats in model+Sem capsules dosing groups decreased significantly after 7 and 14 d of Sem capsules intervention(P<0.05,P<0.01),so did FBG(P<0.01)and the HbA1c level(P<0.01).Meanwhile,FBG and HbA1c levels of rats in model+Sem capsules 1.678 and 2.517 mg·kg-1 groups were not significantly different from those of the normal control group after 14 d of Sem capsules intervention,suggesting that FBG and HbA1c levels were basically restored to normal.Phar-macokinetic results showed that the elimination half-life(t1/2)of Sem in plasma after ig administration of Sem capsules 0.839,1.678,and 2.517 mg·kg-1 for 14 d in rats was 7.40±1.34,7.48±0.33 and(8.23±0.90)h,respectively,the peak concentration(Cmax)was 18±9,81±23 and(256±53)μg·L-1,time to peak(Tmax)was 0.06±0.13,1.56±0.88,(1.50±1.00)h,respectively,the area under the curve(AUC0-t)was 158±76 μg·h·L-1,858±310 and(3795±1539)μg·h·L-1,and the accumulation index was 1.12±0.05,1.12±0.01 and 1.15±0.04,respectively.CONCLUSION Sem capsules ig administrated can effectively reduce body mass,FBG and HbA1c levels in type 2 diabetic model rats,and lead to glucose reduction and by mass loss.After 14 d of continuous administration of Sem capsules,there is no accu-mulation of semaglutide in rats in the dose range of 0.839-2.517 mg·kg-1,and the exposure increases with the dose.