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 investigate the impacts and mechanism of circular RNA polyribonucleotide nucleotidyltransferase 1(Circ-PNPT1)on glucose and lipid metabolism and offspring outcomes in rats with GDM through microRNA-345-3p(miR-345-3p)/lipid raft scaffold protein 2(FLOT2)axis.Methods 75 pregnant female rats were divided into normal control(NC)group,GDM group,si-NC group,si-Circ-PNPT1 group,and si-Circ-PNPT1+miR-345-3p-inhibitor group,with 15 rats in each group.Glucose and lipid metabolism indexes were detected in each group.FIns was detected by ELISA.The survival rate and body weight of fetal rats were compared in each group.The expression of Circ-PNPT1,miR-345-3p and FLOT2 mRNA in placenta was detected by qRT-PCR.The double luciferase reporter gene experiment verified the targeting relationship between miR-345-3p and Circ-PNPT1 and FLOT2.Western blot was used to detect the expression of FLOT2 protein in rat placenta.Results Compared with the NC group,the level of FPG,FIns,HOMA-IR,TC,TG,LDL-C,embryo weight,and the expressions of Circ-PNPT1,FLOT2 in GDM group increased,the level of HDL-C,embryo survival rate and the expression of miR-345-3p decreased(P<0.05).Compared with GDM group,the level of FPG,FIns,HOMA-IR,TC,TG,LDL-C,embryo weight,and the expression of FLOT2 in si-Circ-PNPT1 group decreased,the level of HDL-C,embryo survival rate and the expression of miR-345-3p increased(P<0.05);MiR-345-3p-inhibitor reversed the improvement of si-Circ-PNPT1 on GDM rats(P<0.05).Conclusions Knocking down Circ-PNPT1 can up-regulate miR-345-3p and down-regulate FLOT2 to improve glucose and lipid metabolism and offspring outcome in GDM rats.

Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

Objective To investigate the impacts and mechanism of circular RNA polyribonucleotide nucleotidyltransferase 1(Circ-PNPT1)on glucose and lipid metabolism and offspring outcomes in rats with GDM through microRNA-345-3p(miR-345-3p)/lipid raft scaffold protein 2(FLOT2)axis.Methods 75 pregnant female rats were divided into normal control(NC)group,GDM group,si-NC group,si-Circ-PNPT1 group,and si-Circ-PNPT1+miR-345-3p-inhibitor group,with 15 rats in each group.Glucose and lipid metabolism indexes were detected in each group.FIns was detected by ELISA.The survival rate and body weight of fetal rats were compared in each group.The expression of Circ-PNPT1,miR-345-3p and FLOT2 mRNA in placenta was detected by qRT-PCR.The double luciferase reporter gene experiment verified the targeting relationship between miR-345-3p and Circ-PNPT1 and FLOT2.Western blot was used to detect the expression of FLOT2 protein in rat placenta.Results Compared with the NC group,the level of FPG,FIns,HOMA-IR,TC,TG,LDL-C,embryo weight,and the expressions of Circ-PNPT1,FLOT2 in GDM group increased,the level of HDL-C,embryo survival rate and the expression of miR-345-3p decreased(P<0.05).Compared with GDM group,the level of FPG,FIns,HOMA-IR,TC,TG,LDL-C,embryo weight,and the expression of FLOT2 in si-Circ-PNPT1 group decreased,the level of HDL-C,embryo survival rate and the expression of miR-345-3p increased(P<0.05);MiR-345-3p-inhibitor reversed the improvement of si-Circ-PNPT1 on GDM rats(P<0.05).Conclusions Knocking down Circ-PNPT1 can up-regulate miR-345-3p and down-regulate FLOT2 to improve glucose and lipid metabolism and offspring outcome in GDM rats.

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 predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

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.

Cerebral white matter hyperintensity(WMH)is a type of ischemic alteration that appears as speckled or patchy areas around the ventricles and in the centrocentral area of the semiovals.This alteration can be caused by various factors and indicates a change in the composition of the white matter in the brain.It suggests an alteration in the water content of the hydrophobic white matter fiber bundles.WMH is commonly used as an imaging marker for cerebral small vessel disease.Previous studies have shown that WMH is highly correlated with cognitive impairment.Large-scale longitudinal studies,both population-based and hospital-based,have confirmed the correlation between WMH and clinical symptoms and demonstrated a causal relationship between large-scale WMH and dementia.Adequate differential diagnosis,evaluation,and management are crucial for patients,especially those with early cognitive impairment.Novel imaging techniques may detect subtle impairments before they become visible on an MRI.The purpose of this review is to offer a comprehensive overview of the relationship between WMH and cognitive function.

Background::Mild traumatic brain injury (mTBI) is a common neurological trauma that can lead to cognitive impairment. The sirtuin-1 (SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) pathway has been reported to have neuroprotective effects in rats with craniocerebral injury. We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI, focusing on the SIRT-1/PGC-1α/mitochondrial pathway.Methods::We included forty 6-week-old male Sprague-Dawley rats in this study. Rats were randomly divided into four groups: controlled cortical impactor (CCI, n = 10), sham operation (sham, n = 10), electroacupuncture-treated CCI (CCI+EA, n = 10), and electroacupuncture-treated sham (sham+EA, n = 10) group. Randomization was performed by assigning a random number to each rat and using a random number table. The mTBI rat model was established using a controllable cortical impactor. Electroacupuncture therapy was performed on the back of rats, by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment. We evaluated spatial learning and memory functions with the Morris water maze test. We performed quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, adenosine triphosphate (ATP) determination, and mitochondrial respiratory chain complex I (MRCC I) determination on rat hippocampal tissue. We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays, and compared differences between groups using bilateral Student’s t-tests. Results::Compared with the sham group, SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group ( P <0.01). Although this expression was upregulated following electroacupuncture, it did not reach the levels observed in the sham group ( P <0.05). Compared with the sham group, MRCC I and ATP levels in the CCI group were significantly reduced, and increased after electroacupuncture ( P <0.01). In the Morris water maze, electroacupuncture reduced the incubation period of rats and increased average speed and number of crossing platforms ( P <0.05). Conclusion::Electroacupuncture may improve cognitive function in the mTBI rat model by regulating the SIRT-1/PGC-1α/mitochondrial pathway.