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 summarize the clinicopathological characteristics and prognostic factors of salivary duct carcinoma(SDC)patients.Methods This study was reviewed and approved by the Ethics Committee,and informed consent was obtained from the patients.The clinical data of 30 SDC patients who were admitted to the Fourth Hospital of Hebei Medical University from 2014 to 2022,including case records,pathological diagnoses,immunohistochemical indicators,treatment methods,follow-up data,and other data,were retrospectively analyzed.SPSS 26.0 software was used to process the data and construct relevant curves.The chi-square test was used to analyze the correlation between different immunohistochemical indices and the recurrence and metastasis of SDC,and a single factor was used to ana-lyze clinical prognostic factors.Results Among the 30 SDC patients,the male-to-female ratio was 5∶1,with a median age of 61.5 years.Approximately 60％of cases occurred in the parotid gland,whereas the remainder occurred in the submaxillary gland,sublingual gland,or minor salivary gland.Among them,19 patients were androgen receptor-positive,23 patients were human epidermal growth factor receptor-2 positive,and 26 patients were Ki-67 positive.Postoperative follow-up was 18-94 months,with a median follow-up of 37 months.There were 13 cases of recurrence and 14 cases of distant metastasis.The 5-year overall survival rate was only 31.2％.The long-term survival of patients who underwent postoperative radiotherapy and chemoradiotherapy was better than that of patients who underwent surgery alone(P=0.027).T stage and lymph node invasion were associated with prognosis and survival(P＜0.05).There was a correlation between a Ki-67-positive cell count ≥ 40％and postoperative recurrence or metastasis(P=0.025).Conclusion Radi-cal surgery combined with postoperative radiotherapy and chemoradiotherapy is helpful for improving long-term overall survival,and tumor T stage and lymph node metastasis may be the main factors affecting the prognosis of patients with SDC.Patients with Ki-67-positive cell counts ≥ 40％are prone to postoperative recurrence or metastasis.

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.

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.

Objective To investigate the effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome and its mechanism. Methods A total of 30 male C57 mice were randomly divided into sham-operation group (SHAM group) with 6 mice, sham operation+ metformin group (SHAM+M group) with 5 mice, Budd-Chiari model group (BCS group) with 10 mice, and Budd-Chiari model+metformin group (BCS+M group) with 9 mice. The mice in the model group were treated with partial ligation of the inferior vena cava, those in the SHAM group were not treated with ligation, and those in the metformin group were given 0.1% metformin in drinking water besides modeling. The mice were sacrificed after 6 weeks. HE staining and picrosirius red staining were used to observe liver histopathology and collagen deposition; immunohistochemistry was used to measure the expressions of α-smooth muscle actin (α-SMA) and fibrinogen; quantitative real-time PCR was used to measure the mRNA expression of hypoxia-inducible factor 1α (HIF-1α) and type Ⅰ collagen (collagen 1), and Western blot was used to measure the relative protein expression levels of HIF-1α, vascular endothelial growth factor (VEGF), fibrinogen, α-SMA, and collagen 1. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Pathological staining showed that compared with the SHAM group, the BCS group had significant liver fibrosis, disordered arrangement of hepatocytes near the central vein, sinusoidal expansion with red blood cell deposition and a small amount of inflammatory cell infiltration, and collagen deposition. The BCS group had significant increases in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05); compared with the BCS group, the BCS+M group had significant alleviation of liver fibrosis, red blood cell deposition, and collagen deposition and significant reductions in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05). Conclusion Metformin can improve congestive liver fibrosis caused by Budd-Chiari syndrome, possibly by reducing microthrombus in hepatic sinusoid and inhibiting the HIF-1α/VEGF pathway.

Objective:To study the factors influencing short-term prognosis of patients with Budd-Chiari syndrome (B-CS) presenting with upper gastrointestinal bleeding and to assess the predictive value of platelet-albumin-bilirubin score (PALBI) on death within 30 d in these patients.Methods:A retrospective study was conducted on 74 patients with B-CS who presented with upper gastrointestinal bleeding and were treated at the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020. There were 51 males and 23 females, with age of (46.5±11.1) years old. These patients were divided into the survival group ( n=58) and the death group ( n=16) according to the disease outcomes up to 30 d of follow-up. Factors influencing short-term deaths of these patients were analyzed, and the predictive values of PALBI, ALBI, CTP and MELD scores on short-term prognosis of the patients were assessed. The receiver operating characteristic (ROC) curves were plotted, and the areas under the curve (AUC) were calculated and compared. Results:The differences between patients in the survival and death groups for white blood cell, platelet, PALBI score, PALBI classification, ALBI score, CTP score, MELD score, and presence or absence of hepatic encephalopathy were significantly different (all P<0.05). Multivariate logistic regression analysis showed that CTP score≥10 or CTP grade C ( OR=1.669, 95% CI: 1.048-2.661), and PALBI score >-2.09 or PALBI grade 3 ( OR=5.245, 95% CI: 2.128-12.924) were independent risk factors for predicting death within 30 days. The areas under the ROC curves for PALBI, ALBI, CTP and MELD score were 0.89, 0.72, 0.77 and 0.76, with the cut-off values of -1.92, -1.60, 8.50 and 13.60, respectively. The differences between the PALBI score and ALBI, CTP scores were significantly different ( P<0.05). Conclusion:The PALBI score showed a positive predictive value on short-term prognostic assessment of patients with B-CS presenting with upper gastrointestinal bleeding. It was comparable to the effect of the MELD score but was significantly better than the ALBI and CTP scores.

Objective:To explore the mechanism of mTOR/HIF-1α signaling pathway in Budd-Chiari syndrome (B-CS) liver fibrosis.Methods:Twenty male C57 mice were randomly divided into Sham operation group (Sham), sham operation+ rapamycin (Sham+ Ra) group, B-CS group, B-CS+ rapamycin (B-CS+ Ra) Group, 5 in each group. The B-CS mouse model was constructed by partial ligation of the inferior vena cava(IVC) at the posterior segment of the liver; IVC was not ligated in the Sham group. Mice in Sham+ Ra and B-CS+ Ra groups were intraperitoneally injected with rapamycin (2 mg/kg, 5% DMSO solution preparation) every other day, Sham group and B-CS group were injected with the same dose of 5% DMSO solution.After 6 weeks, samples were taken, and part of the liver tissue was used to make paraffin sections for hematoxylin-eosin (HE) and Sirus Red staining to observe the pathological changes, and immunohistochemical staining to detect the expression of α-SMA and Fibrinogen in liver tissues; Protein and RNA were extracted from fresh liver tissue, and Western-blot was used to detect α-SMA, Fibrinogen, p-mTOR, mTOR, HIF-1α, Collagen I, and VEGF protein levels. Real-time fluorescent quantitative PCR was used to detect mTOR, HIF-1α, CollagenⅠ, VEGF mRNA levels.Measurement data were expressed as mean±standard deviation ( ± s), and the comparison between groups was performed by one-way ANOVA test. Results:The results of pathological staining showed that in the B-CS group, there was severe congestion around the central vein of the liver and sinusoids, widening of the sinus space, and increased collagen deposition, indicating that this study successfully established a mouse B-CS liver fibrosis model. The expression levels of fibrosis indicators α-SMA and Collagen I protein, mTOR pathway related indicators p-mTOR and HIF-1α protein, and microthrombus indicator Fibrinogen protein in the Sham group were 0.027±0.012, 0.337±0.008, 0.138±0.024, 0.296±0.113, 0.733±0.192; B-CS group were 0.986±0.001, 0.927±0.055, 0.936±0.044, 1.693±0.443, 1.612±0.068, and the differences were statistically significant ( P<0.05). The expression levels of B-CS+ Ra group were 0.707±0.078, 0.311±0.024, 0.332±0.094, 0.254±0.117, 0.569±0.075, which were statistically significant compared with B-CS group ( P<0.05). Conclusions:The mTOR/HIF-1α signaling pathway is significantly activated in mouse B-CS liver fibrosis. This pathway may participate in the development of liver fibrosis by regulating microthrombosis.

Objective:To examine the effect of thrombolytic therapy of Budd-Chiari syndrome (B-CS) with inferior vena cava (IVC) thrombosis, and the prognosis factors of it.Methods:The clinical data of 67 patients of B-CS with IVC thrombosis treated in the Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2020 were analyzed retrospectively. There were 30 males and 37 females. The age was (47.7±11.1) years(range: 18 to 72 years). All patients received catheter directed thrombolysis, and the thrombolysis process, complications and outcomes were analyzed. All patients received IVC balloon angioplasty after thrombolytic therapy. The t test, χ 2 test, Mann-Whitney U test were used for univariate analysis of the prognosis factors of thrombolysis effects, while unconditional Logistic regression model were used for multivariate analysis. Results:In the 67 patients, 47 cases succerssed in thrombolytic therapy. The successful rates of thrombolysis at 1-, 2-, 3- and 4-week were 9.0%, 29.9%, 64.2% and 70.1%, respectively. The rates of thrombolytic catheter-related infection at 1-, 2-, 3- and 4-week were 1.5%, 4.5%, 14.9% and 31.3%, respectively. No serious complications such as symptomatic and acute pulmonary embolism occurred during perioperative period of IVC balloon angioplasty. Univariate analysis showed that differences in thrombus length ((36.7±18.1) mm vs. (52.0±16.4) mm, t=-3.234, P=0.002), Child-Pugh classification (class A/B/C: 37/8/2 vs. 10/8/2, Z=-2.310, P=0.021) and pre-opening IVC proportion (68.1% (32/47) vs. 35.0% (7/20), χ2=6.313, P=0.012) were statistically significant. The thrombus length ( OR=0.948, 95% CI: 0.913 to 0.984, P=0.005), pre-opening IVC ( OR=5.451, 95% CI: 1.469 to 20.228, P=0.011) were independent prognosis factors of thrombolytic effect. Conclusions:Thrombolytic therapy for B-CS with IVC thrombosis were satisfactory, and the thrombolysis duration should be confined within 3 weeks. IVC balloon angioplasty is safe and effective for patients failing in thrombolysis, and pre-opening IVC is an important method to improve the thrombolytic effect.

Objective:To examine the effect of thrombolytic therapy of Budd-Chiari syndrome (B-CS) with inferior vena cava (IVC) thrombosis, and the prognosis factors of it.Methods:The clinical data of 67 patients of B-CS with IVC thrombosis treated in the Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2020 were analyzed retrospectively. There were 30 males and 37 females. The age was (47.7±11.1) years(range: 18 to 72 years). All patients received catheter directed thrombolysis, and the thrombolysis process, complications and outcomes were analyzed. All patients received IVC balloon angioplasty after thrombolytic therapy. The t test, χ 2 test, Mann-Whitney U test were used for univariate analysis of the prognosis factors of thrombolysis effects, while unconditional Logistic regression model were used for multivariate analysis. Results:In the 67 patients, 47 cases succerssed in thrombolytic therapy. The successful rates of thrombolysis at 1-, 2-, 3- and 4-week were 9.0%, 29.9%, 64.2% and 70.1%, respectively. The rates of thrombolytic catheter-related infection at 1-, 2-, 3- and 4-week were 1.5%, 4.5%, 14.9% and 31.3%, respectively. No serious complications such as symptomatic and acute pulmonary embolism occurred during perioperative period of IVC balloon angioplasty. Univariate analysis showed that differences in thrombus length ((36.7±18.1) mm vs. (52.0±16.4) mm, t=-3.234, P=0.002), Child-Pugh classification (class A/B/C: 37/8/2 vs. 10/8/2, Z=-2.310, P=0.021) and pre-opening IVC proportion (68.1% (32/47) vs. 35.0% (7/20), χ2=6.313, P=0.012) were statistically significant. The thrombus length ( OR=0.948, 95% CI: 0.913 to 0.984, P=0.005), pre-opening IVC ( OR=5.451, 95% CI: 1.469 to 20.228, P=0.011) were independent prognosis factors of thrombolytic effect. Conclusions:Thrombolytic therapy for B-CS with IVC thrombosis were satisfactory, and the thrombolysis duration should be confined within 3 weeks. IVC balloon angioplasty is safe and effective for patients failing in thrombolysis, and pre-opening IVC is an important method to improve the thrombolytic effect.