GPSAdb: a comprehensive web resource for interactive exploration of genetic perturbation RNA-seq datasets.

Gene knock-out/down methods are commonly used to explore the functions of genes of interest, but a database that systematically collects perturbed data is not available currently. Manual curation of all the available human cell line perturbed RNA-seq datasets enabled us to develop a comprehensive human perturbation database (GPSAdb, https://www.gpsadb.com/). The current version of GPSAdb collected 3048 RNA-seq datasets associated with 1458 genes, which were knocked out/down by siRNA, shRNA, CRISPR/Cas9, or CRISPRi. The database provides full exploration of these datasets and generated 6096 new perturbed gene sets (up and down separately). GPSAdb integrated the gene sets and developed an online tool, genetic perturbation similarity analysis (GPSA), to identify candidate causal perturbations from differential gene expression data. In summary, GPSAdb is a powerful platform that aims to assist life science researchers to easily access and analyze public perturbed data and explore differential gene expression data in depth.

Ultrasmall Metal TPZ Complexes with Deep Tumor Penetration for Enhancing Radiofrequency Ablation Therapy and Inducing Antitumor Immune Responses.

Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for the treatment of solid tumors, but residual malignant tissues or small satellite lesions after insufficient RFA (iRFA) are difficult to remove, often leading to metastasis and recurrence. Here, Fe-TPZ nanoparticles are designed by metal ion and (TPZ) ligand complexation for synergistic enhancement of RFA residual tumor therapy. Fe-TPZ nanoparticles are cleaved in the acidic microenvironment of the tumor to generate Fe2+ and TPZ. TPZ, an anoxia-dependent drug, is activated in residual tumors and generates free radicals to cause tumor cell death. Elevated Fe2+ undergoes a redox reaction with glutathione (GSH), inducing a strong Fenton effect and promoting the production of the highly toxic hydroxyl radical (•OH). In addition, the ROS/GSH imbalance induced by this treatment promotes immunogenic cell death (ICD), which triggers the release of damage-associated molecular patterns, macrophage polarization, and lymphocyte infiltration, thus triggering a systemic antitumor immune response and noteworthy prevention of tumor metastasis. Overall, this integrated treatment program driven by multiple microenvironment-dependent pathways overcomes the limitations of the RFA monotherapy approach and thus improves tumor prognosis. Furthermore, these findings aim to provide new research ideas for regulating the tumor immune microenvironment.

Transcriptional activation of CSTB gene expression by transcription factor Sp3.

CSTB has been reported to be associated with the pathogenesis of many malignant tumors, especially hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated is largely unknown. We initially cloned and analyzed the promoter region of the CSTB gene by luciferase assay and the Sp3 binding site (CCCCGCCCCGCG) was found in it. The results of electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments verified that the transcription factor, Sp3 could bind to the " CCCCGCCCCGCG ″ site of the CSTB gene promoter. We showed that the overexpression of Sp3 significantly increased the endogenous mRNA and protein expression levels of CSTB, whereas knockdown of Sp3 decreased the mRNA and protein expression levels according to quantitative real-time PCR (qRT‒PCR) and western blotting. In conclusion, CSTB gene expression is closely regulated by transcription factor Sp3, which may be a potential mechanism for the dysregulation of CSTB expression in HCC.

Endovascular treatment of aorto-iliac occlusive disease with TASC II C and D lesions: 10 year's experience of clinical technique.

OBJECTIVES: The purpose of this study was to evaluate the therapeutic efficacy and safety of endovascular treatment aorto-iliac occlusive disease (AIOD) with TransAtlantic Inter-Society Consensus II (TASC II) C and D lesions. In addition, 10 years of experience with interventional procedures and treatment options in our center were also worthy of further discussion. METHODS: Between January 2011 and December 2020, a total of 26 consecutive AIOD patients with TASC-II C and D lesions treated endovascular approach were enrolled in this study. Patients' demographic and clinical data were collected, and the safety and efficacy of endovascular therapy were evaluated. In addition, operation procedures were also described. RESULTS: The mean age of patients was 62.2 ± 7 years (49-57 years), and the mean body mass index of patients was 24.2 ± 2.6 kg/m2. Fifteen patients (57.7%) were Rutherford 4, 5 each (19.2%) were Rutherford 3 and 5, and 1 (3.8%) was Rutherford 2. No other serious complications occurred except death in 3 patients. Most of the patients (73.1%) had a history of smoking, and hypertension and hyperlipidemia were common comorbidities. Endovascular therapy was successfully performed in 25 patients, and the technical success rate was 96.2%. The patient's ankle-brachial index improved significantly postoperatively compared with preoperatively (preoperative 0.33 ± 0.14 vs 1.0 ± 0.09, P < 0.001). The primary patency rates were 100%, 95.7%, and 91.3% at 1, 3, and 5 years, while the secondary patency rates were 100%. No treatment-related deaths or serious complications occurred. CONCLUSIONS: Endovascular treatment of AIOD patients with TASC-II C and D lesions might be safe and have a high rate of middle-term and long-term primary patency.

Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice.

BACKGROUND: Astrocytes are essential for synaptic transmission, and their dysfunction can result in neuropsychiatric disorders such as anxiety and depression. Many studies have shown that global knockout of Melatonin receptor 2 (Mtnr1b) is associated with the development of various mental disorders. AIM: This study aimed to investigate the effects of astrocyte ablation of Mtnr1b on cognitive function and anxiety-like behavior in mice, as well as the potential biological mechanisms. METHODS: A conditional Cre-loxP system allowing deletion of Mtnr1b from astrocytes was developed to investigate the specific role Mtnr1b. Control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were selected for cognitive function behavioral testing (Morris water maze test, novel object recognition test) and emotion-related behavioral testing (open field, elevated plus maze). After testing, brain tissue was collected and examined by immunofluorescence for the expression of neuronal nuclei (NeuN), glutamate decarboxylase 67 (GAD67), and vesicular glutamate transporter 1 (vGluT1). RNA-seq was performed on hippocampal tissue from control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice to identify differentially expressed genes. Additional confirmation of differential gene expression was performed using real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were not significantly different from control mice in the Morris water maze and novel object recognition tests. Results from the open field and elevated plus maze tests showed that Mtnr1b cKO𝐺𝑓𝑎𝑝 mice exhibited significantly more anxiety-like behavior than did controls. Immunofluorescence revealed that the number of mature neurons did not differ significantly between Mtnr1b cKO𝐺𝑓𝑎𝑝 mice and controls. The expression of GAD67 in the hippocampal CA1 and CA3 areas of Mtnr1b cKO𝐺𝑓𝑎𝑝 mice was significantly lower than in the control group, but no significant difference was detected for vGluT1 expression. RNA-seq and qRT-PCR results showed that Mtnr1b knockout in astrocytes led to a decrease in the levels of gamma-aminobutyric acid sub-type A (GABAA) receptors and Kir2.2. CONCLUSIONS: The astrocyte-specific knockout in Mtnr1b cKO𝐺𝑓𝑎𝑝 mice results in anxiety-like behavior, which is caused by down-regulation of gamma-aminobutyric acid-ergic (GABAergic) synaptic function.

Endovascular Treatment of Subclavian Artery Pseudoaneurysm.

BACKGROUND: In recent years, endovascular treatment of subclavian artery pseudoaneurysm (SAP) has been recommended by many experts. The aim of this study is to evaluate the safety and efficacy of the endovascular treatment of SAP, and to introduce our experience in the diagnosis and treatment of SAP. METHODS: A total of 8 consecutive patients with SAP were treated with endovascular treatment in our hospital between 2010 and 2018. We retrospectively reviewed the patients' clinical characteristics, physical examinations findings, diagnostic imaging results, endovascular treatment, clinical outcome, and follow-up results. RESULTS: All the 8 patients received endovascular treatment with covered stents initially. The technical success rate was 87.5% (7/8). In 1 patient with severe tortuosity of the proximal subclavian artery, the stent could not be released through the femoral artery approach in the primary operation but was successfully released via the brachial artery approach in the secondary operation. No complications occurred in the perioperative period. All the symptoms and signs were significantly relieved. During a follow-up of 4.5-84.5 months (average 31.5 months), 1 patient developed an endoleak 4 months after operation and reintervention was attempted but failed. No adverse events occurred in other patients during the follow-up period. CONCLUSIONS: Endovascular treatment of SAP is safe and effective, and should be used as a first-line treatment. Stent placement through the brachial artery approach is recommended for SAP with severe proximal vascular tortuosity.

Spontaneous recanalization of occluded transplant renal artery: a rare case report.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a serious vascular complication that occurs after renal transplantation and can result in hypertension, renal functional impairment, and graft loss. Endovascular treatment has become the first-line treatment for TRAS because of its low invasiveness and high success rate. CASE PRESENTATION: A 23-year-old female with end-stage renal disease of unknown cause received a living-donor kidney transplantation 10 months ago. Seven months after the transplantation, her blood pressure gradually deteriorated. Magnetic resonance angiography revealed bending and stenosis of the transplant renal artery, and the patient received endovascular treatment. A digital subtraction angiography revealed significant stenosis of 95% in the proximal transplant renal artery. The guidewire could not pass through the stenotic segment of the transplant renal artery even with repeated attempts by the surgeons; as a result, the transplant renal artery became occluded, and vasodilators were ineffective. After the operation, renal function gradually worsened, so she began to receive regular dialysis. Twenty-five days later, the patient's urine volume was significantly higher than that before, and ultrasound showed that the proximal transplant renal artery was not completely occluded. A re-intervention was performed, and the stent was placed successfully in the stenotic segment. After the operation, renal function gradually recovered, and dialysis was no longer needed. CONCLUSION: Patients with iatrogenic transplant renal artery occlusion may have the possibility of spontaneous recanalization, which can help prevent the need for re-transplantation.

Segmenting Microscopy Images of Multi-Well Plates Based on Image Contrast.

Image segmentation is a key process in analyzing biological images. However, it is difficult to detect the differences between foreground and background when the image is unevenly illuminated. The unambiguous segmenting of multi-well plate microscopy images with various uneven illuminations is a challenging problem. Currently, no publicly available method adequately solves these various problems in bright-field multi-well plate images. Here, we propose a new method based on contrast values which removes the need for illumination correction. The presented method is effective enough to distinguish foreground and therefore a model organism (Caenorhabditis elegans) from an unevenly illuminated microscope image. In addition, the method also can solve a variety of problems caused by different uneven illumination scenarios. By applying this methodology across a wide range of multi-well plate microscopy images, we show that our approach can consistently analyze images with uneven illuminations with unparalleled accuracy and successfully solve various problems associated with uneven illumination. It can be used to process the microscopy images captured from multi-well plates and detect experimental subjects from an unevenly illuminated background.

A Context-Aware Mobile User Behavior-Based Neighbor Finding Approach for Preference Profile Construction.

In this paper, a new approach is adopted to update the user preference profile by seeking users with similar interests based on the context obtainable for a mobile network instead of from desktop networks. The trust degree between mobile users is calculated by analyzing their behavior based on the context, and then the approximate neighbors are chosen by combining the similarity of the mobile user preference and the trust degree. The approach first considers the communication behaviors between mobile users, the mobile network services they use as well as the corresponding context information. Then a similarity degree of the preference between users is calculated with the evaluation score of a certain mobile web service provided by a mobile user. Finally, based on the time attenuation function, the users with similar preference are found, through which we can dynamically update the target user's preference profile. Experiments are then conducted to test the effect of the context on the credibility among mobile users, the effect of time decay factors and trust degree thresholds. Simulation shows that the proposed approach outperforms two other methods in terms of Recall Ratio, Precision Ratio and Mean Absolute Error, because neither of them consider the context mobile information.

Correction: Gao, Q. et al. A Context-Aware Mobile User Behavior-Based Neighbor Finding Approach for Preference Profile Construction. Sensors 2016, 2, 143.

At first, may I offer my profoundest respects to the previous work obtained by the author Shi, whose work enlarged our view and set a good research direction for us and enlightened the initial idea of our paper.[...].

Effect of Transcatheter Intra-Arterial Therapies on Tumor Interstitial Fluid Pressure and Its Relation to Drug Penetration in a Rabbit Liver Tumor Model.

PURPOSE: To determine the change in tumor interstitial fluid pressure (IFP) after transcatheter intra-arterial (IA) therapies and its relation to drug penetration in liver cancer. MATERIALS AND METHODS: VX2 tumors were grown in the livers of 16 rabbits. The rabbits were treated with intravenous injection of doxorubicin (group 1; n = 4), hepatic IA injection of doxorubicin (group 2; n = 4), hepatic IA injection of doxorubicin followed by embolization with polyvinyl alcohol particles (group 3; n = 4), or hepatic IA injection of doxorubicin mixed with Lipiodol followed by polyvinyl alcohol embolization (group 4; n = 4). Tumor IFP was measured with a Mikro-Tip pressure catheter before and 1 hour after treatment. Doxorubicin penetration was evaluated by immunofluorescence. RESULTS: Tumor IFP after treatment decreased by 5.0% ± 2.8, 3.9% ± 9.0, 27.1% ± 5.2, and 31.8% ± 7.4 in groups 1-4, respectively. The difference in IFP reduction between embolization-treated groups (groups 3 and 4) and nonembolized groups (groups 1 and 2) was significant (P < .001). Doxorubicin penetration distances were 20.3 µm ± 3.7, 45.7 µm ± 10.5, 69.5 µm ± 9.3, and 47.9 µm ± 6.4 in groups 1-4, respectively. IFP reduction was significantly correlated with doxorubicin penetration distance (r = .671, P = .004). CONCLUSIONS: A greater reduction of tumor IFP was associated with embolization in a preclinical liver tumor model, and embolization may indirectly contribute to increased drug penetration.

Clinical features and endovascular treatment of visceral artery pseudoaneurysms.

BACKGROUND: To analyze our experience with clinical features and endovascular treatment of visceral artery pseudoaneurysms (VAPAs). METHODS: We performed endovascular treatments on 52 patients (34 men and 18 women) affected by VAPA. These cases were pseudoaneurysms of the celiac axis, superior mesenteric artery, and their branches. Endovascular treatments of VAPA using isolation techniques were performed after failure of conservative treatments. Follow-up was carried out via assessment of contrast-enhanced computed tomography or computed tomography angiography images. RESULTS: The initial technical success rate of endovascular treatment is 100% with only 4 patients rebled during 2-week follow-up. One patient among no rebleeding died of multisystem organ failure 28 days after intervention; thus, 30-day mortality rate was 1.9%. Four patients (7.7%) required secondary interventions because of rebleeding and were successfully treated by reintervention; however, one of the patients died from uncontrolled sepsis 39 days after reintervention. Postembolization syndrome developed in 3 patients (5.8%); one of these patients underwent splenectomy. During follow-up, no change of hepatic function was observed, no bowel ischemia was reported, and VAPA remained absent in all patients. CONCLUSIONS: Endovascular management is minimally invasive and highly successful in treating VAPA. It is particularly useful in poor surgical candidates.

CSTB accelerates the progression of hepatocellular carcinoma via the ERK/AKT/mTOR signaling pathway.

Hepatocellular carcinoma (HCC) is a significant contributor to global cancer-related deaths, leading to high mortality rates. However, the pathogenesis of HCC remains unclear. In this research, by the bioinformatics data analysis, we found that elevated CSTB expression correlated with advanced disease and predicted diminished overall survival (OS) in HCC patients. We subsequently verified the oncogenic role of CSTB as well as the potential underlying mechanisms in HCC through a series of in vitro experiments, such as CCK-8 assays, cloning assays, flow cytometry, Transwell assays, and western blotting. Our findings illustrated that the silencing of CSTB effectively suppressed cellular proliferation by inducing cell cycle arrest in the G2 phase and impaired HCC cell invasion and migration by stimulating epithelial-mesenchymal transition (EMT). Additionally, we analyzed the pathways enriched in HCC using RNA sequencing and found that the ERK/AKT/mTOR signaling pathway was related to increased CSTB expression in HCC. Finally, we confirmed the tumorigenic role of CSTB via in vivo experiments. Thus, our findings revealed that silencing CSTB inhibited the HCC progression via the ERK/AKT/mTOR signaling pathway, highlighting new perspectives for investigating the mechanisms of HCC.

scCAN: Clustering With Adaptive Neighbor-Based Imputation Method for Single-Cell RNA-Seq Data.

Single-cell RNA sequencing (scRNA-seq) is widely used to study cellular heterogeneity in different samples. However, due to technical deficiencies, dropout events often result in zero gene expression values in the gene expression matrix. In this paper, we propose a new imputation method called scCAN, based on adaptive neighborhood clustering, to estimate the zero value of dropouts. Our method continuously updates cell-cell similarity information by simultaneously learning similarity relationships, clustering structures, and imposing new rank constraints on the Laplacian matrix of the similarity matrix, improving the imputation of dropout zero values. To evaluate the performance of this method, we used four simulated and eight real scRNA-seq data for downstream analyses, including cell clustering, recovered gene expression, and reconstructed cell trajectories. Our method improves the performance of the downstream analysis and is better than other imputation methods.

Drug-eluting beads transarterial chemoembolization combined apatinib/camrelizumab for advanced hepatocellular carcinoma with hepatic arterioportal shunts.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (D-TACE) combined with apatinib/camrelizumab in advanced hepatocellular carcinoma (HCC) patients with hepatic arterioportal shunts (APS). METHODS: From January 2021 to December 2022, consecutive medical records of advanced HCC patients with APS receiving D-TACE combined apatinib/camrelizumab were reviewed for eligibility. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) were assessed. RESULTS: A total of 23 patients were included in this study, and the median follow-up time was 11 months (range, 2-26 months). In this study, 8 patients (34.8%) achieved PR, 13 patients (56.5%) achieved SD, and 2 patients (8.7%) developed PD. The objective response rate and disease controlled rate were 34.8% and 91.3%, respectively. OS and PFS were 11 months and 7 months, respectively. Multivariate analysis indicated that tumor number was an independent prognostic factor affecting PFS. AEs occurred in 19 patients after oral apatinib and in 8 patients after camrelizumab treatment. No treatment-related death occurred. CONCLUSIONS: D-TACE combined with apatinib/camrelizumab had meaningful efficacy and controllable AEs in advanced HCC patients with APS, which may be a promising treatment option. ADVANCES IN KNOWLEDGE: •1.We investigate a new treatment strategy for advanced HCC patients with hepatic arterioportal shunts；2.D-TACE combined with apatinib/camrelizumab had meaningful efficacy and controllable AEs in advanced HCC patients with APS, which may be a promising treatment option.

The time window for pre-emptive transjugular intrahepatic portosystemic shunt could be extended to 5 days.

As recommended by Baveno VII consensus, the utilization of pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) has been considered as standard therapeutic approach for the management of acute variceal bleeding (AVB) associated with cirrhosis., but the 72-h window for pTIPS is too narrow. This study aimed to compare the clinical outcomes between patients who received <72 h pTIPS and 72 h-5d pTIPS. In this study, a total of 63 cirrhotic patients with AVB who underwent pTIPS between October 2016 and December 2021 were included in this retrospective study. They were divided into <72 h group (n = 32) and 72 h-5d group (n = 31), based on the timing of the intervention. The Kaplan-Meier curves demonstrated that there were no significant differences in the cumulative incidence of death (22.3% ± 7.4% vs. 19.9% ± 7.3%, log-rank P = 0.849), variceal rebleeding (9.7% ± 5.3% vs. 17.8% ± 7.3%, log-rank P = 0.406), OHE (28.5% ± 8.0% vs. 23.9% ± 8.0%, log-rank P = 0.641) and shunt dysfunction (8.6% ± 6.0% vs. 17.4% ± 8.1%, log-rank P = 0.328) between <72 h and 72 h-5d groups. In the total cohort, sarcopenia was identified as an independent risk factor for mortality (HR = 11.268, 95% CI = 1.435-88.462, P = 0.021) and OHE(HR = 12.504, 95% CI = 1.598-97.814, P = 0.016). In conclusion, the clinical outcomes of cirrhotic patients with AVB who underwent pTIPS within the 72-h to 5-day window were found to be comparable to those treated within the 72-h window.

SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aß generation.

SIL1, an endoplasmic reticulum (ER)-resident protein, is reported to play a protective role in Alzheimer's disease (AD). However, the effect of SIL1 on amyloid precursor protein (APP) processing remains unclear. In this study, the role of SIL1 in APP processing was explored both in vitro and in vivo. In the in vitro experiment, SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695. In the in vivo experiment, AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates. Western blotting (WB), immunohistochemistry, RNA sequencing (RNA-seq), and behavioral experiments were performed to evaluate the relevant parameters. Results indicated that SIL1 expression decreased in APP23/PS45 mice. Overexpression of SIL1 significantly decreased the protein levels of APP, presenilin-1 (PS1), and C-terminal fragments (CTFs) of APP in vivo and in vitro. Conversely, knockdown of SIL1 increased the protein levels of APP, ß-site APP cleavage enzyme 1 (BACE1), PS1, and CTFs, as well as APP mRNA expression in 2EB2 cells. Furthermore, SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice. Importantly, Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice. These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

Impact of Sarcopenia on Prognosis in Primary Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization: A Single Center Retrospective Study.

Objective: This study aimed to investigate the prognostic effect of sarcopenia on primary hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE). Methods: This retrospective study enrolled 265 patients diagnosed with HCC who underwent TACE between April 2014 and February 2021. The patients were divided into two groups: the sarcopenia group (n=133) and the non-sarcopenia group (n=132). The study analyzed the differences in overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curves. The independent risk factors for OS and PFS were determined using univariate and multivariate Cox regression analysis. Based on these factors, the study constructed a prognostic risk grading system. Results: At 3 and 6 months post-TACE, the prognoses of the sarcopenia group were worse than that of the non-sarcopenia group according to the mRECIST criteria. Kaplan-Meier curves showed that the cumulative OS and PFS rate in the non-sarcopenia group were significantly higher compared to the sarcopenia group (HR=3.319, 95%CI: 2.283-4.824, Log-rank P < 0.001; HR=0.631, 95%CI: 0.486-0.820, Log-rank P < 0.001). Sarcopenia, maximal tumor diameter, and AFP ≥ 200 ng/mL were independent risk factors for OS and PFS. The prognostic risk grading system based on sarcopenia, AFP ≥ 200 ng/mL, and maximal tumor diameter≥8.9 cm showed significant differences in prognosis between risk groups. Conclusion: Sarcopenia had excellent predictive value for OS and PFS in patients after TACE, and AFP ≥ 200 ng/mL and maximal tumor diameter were also independent risk factors for a poor prognosis. The prognostic risk grading system based on sarcopenia, AFP, and maximal tumor diameter had good guiding value for the prognosis of patients.

Synergistic Effects of Nanoscale CaO2 Combined with PD-1 Inhibitors in the Treatment of Hepatocellular Carcinoma: A Promising Combination.

Purpose: To explore the effect of calcium peroxide nanoparticles (CaO2 NPs) combined with programmed cell death protein 1 (PD-1) inhibitors in the treatment of liver cancer and its related mechanism. Methods: Hepa1-6 cells were cultured to construct the Hepa1-6 mouse liver cancer model. In vivo mechanism study, a unilateral tumor model was established. Eighteen tumor-bearing mice were randomly divided into the control group (intra-tumoral injection of PBS solution) and the experimental group (intra-tumoral injection of CaO2 NPs). A hypoxic probe, pH probe, and micro-CT were used to evaluate the effect of CaO2 NPs on improving hypoxia, neutralizing acidity, and inducing calcium overload within the tumor. To study the effect of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors, the bilateral tumor model was established. Forty tumor-bearing mice were randomly divided into the control group (intra-tumoral/intra-peritoneal injection of PBS solution), CaO2 NPs group (intra-tumoral injection of CaO2 NPs), PD-1 group (intra-peritoneal injection of PD-1 inhibitor), and the combination group (intra-tumoral injection of CaO2 NPs and intra-peritoneal injection of PD-1 inhibitors). The administered side was recorded as the proximal tumor. Tumor volume and body weight were measured every 2 days after treatment. On day 8, serum and tumor samples were collected. The immune factors in serum (Interferon-γ (IFN-γ), Tumour necrosis factor-α (TNF-α), Interleukin-2 (IL-2), and Interleukin-10 (IL-10)) and tumor tissue (IFN-γ and TNF-α) were detected by ELISA. H&E staining was used to detect tumor necrosis. Immunohistochemical staining was used to detect the amount of CD4+ and CD8+ T cells within the tumor. By analyzing the tumor volume, pathological indexes, and immune-related indexes, the effects of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors were evaluated, and they mediated immunomodulatory effects (including local and systemic immunity), and their effects on tumor burden were studied. In addition, a unilateral tumor model was established to study the effect of CaO2 NPs combined with PD-1 inhibitors on survival time. Results: The results of in vivo mechanism study showed that CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors. The results of the study on the effect of CaO2 NPs combined with PD-1 inhibitor on proximal and distal tumors showed that, compared with the other three groups, the bilateral tumor burden of the combination group was significantly reduced, the intra-tumoral infiltration of CD8+ and CD4+ T cells were significantly increased, the secretion of anti-tumor immune factors in tumor and serum was increased, and the secretion of pro-tumor immune factors was decreased. Mice in the combination group showed the longest survival compared with the other groups. Conclusion: CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors, so as to reduce tumor burden and realize an immunosuppressive tumor transformation to a hot tumor, and play a synergistic role with PD-1 inhibitors in anti-liver cancer.