Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

Objective To analyze the awakening effect of transcutaneous auricular vagus nerve stimulation(taVNS)combined with multi-sensory environmental stimulation in patients with persistent vegetative state(PVS).Methods Sixty PVS patients were selected as study subjects,and randomly divided into control group(n=30)and observation group(n=30).Three patients in the control group shed 3 cases and eventually included 27 cases,and the observation group shed 2 cases and e-ventually included 28 cases.Both groups received basic treatment and routine rehabilitation training.The observation group was treated with multi-sensory environmental stimulation combined with taVNS,while the control group received multi-sensory environmental stimulation combined with sham stimula-tion.Both groups were treated once per day,five times per week,for eight consecutive weeks.The Glasgow Coma Scale(GCS)and the Coma Recovery Scale-Revised(CRS-R)scores were compared between the two groups before treatment,after 4,8 weeks of treatment and during follow-up(12 weeks).The electroencephalogram(EEG)grading was analyzed before and after 8 weeks of treat-ment.The awakening effect during follow-up was compared between the two groups.Results After 4,8 weeks of treatment and during follow-up,the GCS and CRS-R scores of both groups were signifi-cantly higher than before treatment,and the observation group had significantly higher scores than the control group(P＜0.05).After 8 weeks of treatment,the EEG grading of both groups was signifi-cantly better than before treatment,and the observation group was significantly better than the control group(P＜0.05).During follow-up,the awakening rate in the observation group was 46.43％,which was significantly higher than 29.63％in the control group(P＜0.05).Conclusion The method of taVNS combined with multi-sensory environmental stimulation has a good awakening effect in PVS patients,and can improve their level of consciousness disorder with high safety.

Objective:To explore the prognostic differences between liver resection and transarterial chemoembolization (TACE) in patients with Budd-Chiari syndrome (BCS) complicated by hepatocellular carcinoma (HCC) and to identify independent risk factors affecting patient survival.Methods:The clinical and follow-up data of 103 patients with stage Ⅰa-Ⅲa BCS complicated by HCC treated at the First Affiliated Hospital of Zhengzhou University from Aug 2015 to Sep 2023 were retrospectively analyzed.Results:Patients were divided into two groups based on their initial treatment choices: the liver resection group ( n=20) and the TACE group ( n=83). Before propensity score matching(PSM), the median overall survival in the liver resection group was 42 months longer than in the TACE group (74 months vs. 32 months, P=0.002). After PSM, the median overall survival remained significantly longer in the liver resection group by 39 months (74 months vs. 35 months, P=0.032). In terms of disease-free survival, before PSM, the liver resection group was 30-month longer than the TACE group (42 months vs. 12 months, P=0.001). After PSM, the difference in median disease-free survival between the two groups was 23 months (35 months vs. 12 months, P=0.018). Multivariate Cox regression analysis identified treatment modality and maximum tumor diameter as independent risk factors for overall survival, while treatment modality was the only independent factor for disease-free survival. Conclusions:Liver resection significantly prolongs both overall survival and disease-free survival in resectable HCC in BCS patients compared to TACE. Treatment modality and tumor size are key prognostic factors influencing overall survival.

OBJECTIVE To investigate the distribution characteristics and drug resistance of multidrug-resistant Acinetobacter baumannii(MDRAB)detected clinically in the Army 73rd Group Military Hospital in Xiamen,and to study the carrying conditions of drug-resistant gene-related insertion sequence elements(IS)and transposons(Tn)in the isolated strains of MDRAB.METHODS A total of 300 strains of Acinetobacter baumannii detected from inpatients admitted to the Army 73rd Group Military Hospital from Jan.2016 to Feb.2024 were collected.Automatic bacterial identification instruments and drug susceptibility tests were used for bacterial identi-fication and drug resistance analysis.Polymerase chain reaction(PCR)was employed to detect 6 Tn genetic mark-ers(merA,TnpU,TnpM,TnpR,TnpA21,TnpA7)and 3 IS genes(ISEcp1,ISCR1,IS26)in MDRAB strains.The detected IS and Tn-positive genes were subjected to sequencing and alignment verification.RESULTS Among 300 Acinetobacter baumannii strains,49(16.33％)were MDRAB.Most MDRAB strains were found in patients aged 75 and above(44.90％),mainly isolated from the brain center ICU(34.69％),critical care medi-cine ICU(20.41％),and respiratory medicine department(16.33％),sputum specimens accounted for the ma-jority(77.55％).MDRAB strains exhibited high drug resistance rates(≥97％)to cefpodoxime,nitrofurantoin,and aztreonam.MDRAB strains showed drug resistance rates＞80％to most antimicrobial agents,but were sensi-tive to polymyxin(12.24％)and tigecycline(28.57％).Compared with non-MDRAB strains,there were statisti-cally significant differences in drug resistance to common antimicrobial agents(P＜0.05).Among MDRAB strains,ISCR1,IS26,TnpU and TnpM genes were detected in IS and Tn,with detection rates of 51.02％,48.98％,51.02％and 22.45％,respectively.merA,TnpR,TnpA21,TnpA7 and ISEcp1 were not detected.CONCLUSIONS The drug resistance of Acinetobacter baumannii is severe,especially in elderly and criti-cally ill patients.The transmission of MDRAB strains may be associated with the genes ISCR1,IS26,TnpM and TnpU.

OBJECTIVE To investigate the distribution characteristics and drug resistance of multidrug-resistant Acinetobacter baumannii(MDRAB)detected clinically in the Army 73rd Group Military Hospital in Xiamen,and to study the carrying conditions of drug-resistant gene-related insertion sequence elements(IS)and transposons(Tn)in the isolated strains of MDRAB.METHODS A total of 300 strains of Acinetobacter baumannii detected from inpatients admitted to the Army 73rd Group Military Hospital from Jan.2016 to Feb.2024 were collected.Automatic bacterial identification instruments and drug susceptibility tests were used for bacterial identi-fication and drug resistance analysis.Polymerase chain reaction(PCR)was employed to detect 6 Tn genetic mark-ers(merA,TnpU,TnpM,TnpR,TnpA21,TnpA7)and 3 IS genes(ISEcp1,ISCR1,IS26)in MDRAB strains.The detected IS and Tn-positive genes were subjected to sequencing and alignment verification.RESULTS Among 300 Acinetobacter baumannii strains,49(16.33％)were MDRAB.Most MDRAB strains were found in patients aged 75 and above(44.90％),mainly isolated from the brain center ICU(34.69％),critical care medi-cine ICU(20.41％),and respiratory medicine department(16.33％),sputum specimens accounted for the ma-jority(77.55％).MDRAB strains exhibited high drug resistance rates(≥97％)to cefpodoxime,nitrofurantoin,and aztreonam.MDRAB strains showed drug resistance rates＞80％to most antimicrobial agents,but were sensi-tive to polymyxin(12.24％)and tigecycline(28.57％).Compared with non-MDRAB strains,there were statisti-cally significant differences in drug resistance to common antimicrobial agents(P＜0.05).Among MDRAB strains,ISCR1,IS26,TnpU and TnpM genes were detected in IS and Tn,with detection rates of 51.02％,48.98％,51.02％and 22.45％,respectively.merA,TnpR,TnpA21,TnpA7 and ISEcp1 were not detected.CONCLUSIONS The drug resistance of Acinetobacter baumannii is severe,especially in elderly and criti-cally ill patients.The transmission of MDRAB strains may be associated with the genes ISCR1,IS26,TnpM and TnpU.

Objective:To explore the prognostic differences between liver resection and transarterial chemoembolization (TACE) in patients with Budd-Chiari syndrome (BCS) complicated by hepatocellular carcinoma (HCC) and to identify independent risk factors affecting patient survival.Methods:The clinical and follow-up data of 103 patients with stage Ⅰa-Ⅲa BCS complicated by HCC treated at the First Affiliated Hospital of Zhengzhou University from Aug 2015 to Sep 2023 were retrospectively analyzed.Results:Patients were divided into two groups based on their initial treatment choices: the liver resection group ( n=20) and the TACE group ( n=83). Before propensity score matching(PSM), the median overall survival in the liver resection group was 42 months longer than in the TACE group (74 months vs. 32 months, P=0.002). After PSM, the median overall survival remained significantly longer in the liver resection group by 39 months (74 months vs. 35 months, P=0.032). In terms of disease-free survival, before PSM, the liver resection group was 30-month longer than the TACE group (42 months vs. 12 months, P=0.001). After PSM, the difference in median disease-free survival between the two groups was 23 months (35 months vs. 12 months, P=0.018). Multivariate Cox regression analysis identified treatment modality and maximum tumor diameter as independent risk factors for overall survival, while treatment modality was the only independent factor for disease-free survival. Conclusions:Liver resection significantly prolongs both overall survival and disease-free survival in resectable HCC in BCS patients compared to TACE. Treatment modality and tumor size are key prognostic factors influencing overall survival.

Objective:To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value.Methods:This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group ( n=38) and the survival group ( n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model′s differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results:Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors ( P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions:The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

Abstract: Cancer immunotherapy, which is an attractive strategy harnessing the host's own immune system to remove tumor cells, has been widely used in clinical practice, yet with low response rate and immune-related adverse events. Unlike traditional chemotherapy, the targets of immunotherapy exhibit high spatial heterogeneity and are distributed in different cell types or secondary organelles, resulting in off-target and on-target toxicity, which greatly reduces the efficacy and safety of treatment. Due to the altered metabolic level, tumor tissues often display a lower pH than normal tissues. In addition, the endocytosis pathway is accompanied by continuous pumping of protons. Therefore, the variation of environmental pH values could serve as an ideal stimulus for precise drug delivery and release. In recent years, pH-responsive materials (e.g., polymers, biomacromolecules, lipid nanoparticles, biofilm, inorganic nanoparticles, and metal-organic frameworks) have been widely investigated in the field of cancer immunotherapy. This paper summarizes recent strategies of pH-responsive drug delivery systems based on different types of carriers, aiming to provide some reference for the design of next generation of tumor-targeting formulations in cancer immunotherapy.

Objective:To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value.Methods:This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group ( n=38) and the survival group ( n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model′s differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results:Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors ( P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions:The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

Objective:To investigate the predictive value of controlled nutritional status (CONUT) score for overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosys-temic stent-shunt (TIPSS) in Budd-Chiari syndrome patients.Method:The retrospective case-control study was conducted. The clinicopathological data of 48 Budd-Chiari syndrome patients who underwent TIPSS in the First Affiliated Hospital of Zhengzhou University from August 2014 to March 2021 were collected. There were 26 males and 22 females, aged (46±13)years. Observation indicators: (1) surgical situations and follow-up; (2) analysis of influencing factors of OHE after TIPSS; (3) predic-tion of OHE after TIPSS. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was performed using the t test. Measurement data with skewed distribution were represented by M( Q1, Q3), and comparison between groups was performed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Multivariate analysis was performed using the Logistic regression model with forward method. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the efficacy. Comparison among AUC was performed using the Delong test. Results:(1) Surgical situations and follow-up. All 48 patients underwent TIPSS successfully, and the operation time of the 48 patients was (131±29)minutes. All patients were implanted with 8 mm covered stent. All 48 patients were followed up for 46(25,71)months, and there were 14 cases with OHE and 34 cases without OHE after TIPSS. Of the 14 cases with OHE, 12 cases were evaluated as West-Haven Ⅱ grade and 2 cases were evaluated as West-Haven Ⅲ grade. (2) Analysis of influencing factors of OHE after TIPSS. Results of multivariate analysis showed that history of hepatic encephalo-pathy and CONUT score were independent factors influencing the incidence of OHE of Budd-Chiari syndrome patients who underwent TIPSS ( odds ratio=8.36, 1.74, 95% confidence interval as 1.02?68.75, 1.12?2.69, P<0.05). (3) Prediction of OHE after TIPSS. Results of ROC curve showed that the AUC of the CONUT score, the Child-Pugh score of liver function and the integrated model of end-stage liver disease (iMELD) score in predicting the incidence of OHE after TIPSS was 0.77(95% confidence interval as 0.64?0.91, P<0.05), 0.71(95% confidence interval as 0.56?0.87, P<0.05) and 0.71(95% confidence interval as 0.53?0.88, P<0.05), respectively, and there was no significant difference between the AUC of the CONUT score and the Child-Pugh score of liver function or the iMELD score ( Z=0.84, 0.59, P>0.05). The optimal cutoff value of CONUT score in predicting the incidence of OHE after TIPSS was 7, with the sensitivity, specificity and Yodon index as 78.6%, 61.8% and 0.40, respectively. Conclusion:The CONUT score can be used to predict the incidence of OHE in Budd-Chiari syndrome patients who underwent TIPSS, and the discrimination of CONUT score is equivalent to the Child-Pugh score of liver function and the iMELD score.