Translational PET Imaging of Nectin-4 Expression in Multiple Different Cancers with 68Ga-N188.

Nectin cell adhesion molecule 4 (nectin-4) is a transmembrane protein overexpressed on a variety of cancers and plays an important role in oncogenic and metastatic processes. The nectin-4-targeted antibody-drug conjugate enfortumab vedotin has been approved for treating locally advanced or metastatic urothelial cancer, but the efficacy in other types of cancer remains to be explored. The aim of this study was to evaluate the feasibility of nectin-4-targeted PET imaging with 68Ga-N188 as a noninvasive method to quantify membranous nectin-4 expression in multiple tumor types-an approach that may provide insight for patient stratification and treatment selection. Methods: Sixty-two patients with 16 types of cancer underwent head-to-head 68Ga-N188 and 18F-FDG PET/CT imaging for initial staging or detection of recurrence and metastases. Correlation between lesion SUVmax and nectin-4 expression determined by immunohistochemistry staining was analyzed in 36 of 62 patients. Results: The SUVmax of 68Ga-N188 had a positive correlation with membranous nectin-4 expression in the various tumor types tested (r = 0.458; P = 0.005), whereas no association was observed between the SUVmax and cytoplasmic nectin-4 expression. The detection rates for patient-based analysis of 68Ga-N188 and 18F-FDG PET/CT examinations were comparable (95.00% [57/60] vs. 93.33% [56/60]). In patients with pancreatic cancer, 68Ga-N188 exhibited a potential advantage for detecting residual or locally recurrent tumors; this advantage may assist in clinical decision-making. Conclusion: The correlation between nectin-4-targeted 68Ga-N188 PET imaging and membranous nectin-4 expression indicates the potential of 68Ga-N188 as an effective tool for selecting patients who may benefit from enfortumab vedotin treatment. The PET imaging results provided evidence to explore nectin-4-targeted therapy in a variety of tumors. 68Ga-N188 may improve the restaging of pancreatic cancer but requires further evaluation in a powered, prospective setting.

Hypoxia-induced epigenetic regulation of miR-485-3p promotes stemness and chemoresistance in pancreatic ductal adenocarcinoma via SLC7A11-mediated ferroptosis.

The mechanism of hypoxia in chemoresistance of pancreatic ductal adenocarcinoma (PDAC) remains elusive. In this study, we revealed the essential role of miR-485-3p in PDAC, particularly its impact on cancer stemness and gemcitabine resistance under hypoxic conditions. We found substantial downregulation of miR-485-3p in PDAC tissues, with lower expression correlating to poor patient outcomes. Mechanistically, miR-485-3p influenced stemness characteristics, as evidenced by reduced tumor-sphere formation and increased sensitivity to gemcitabine upon overexpression. Moreover, we identified SOX9 and SLC7A11 as two targets of miR-485-3p, which play a vital role in stemness and ferroptosis. Under the hypoxic condition, DNMT3B expression was upregulated, leading to hypermethylation of the miR-485-3p promoter region. The reduced miR-485-3p expression promoted stemness and chemoresistance of PDAC. In conclusion, our findings elucidate the intricate interplay of hypoxia, epigenetic modifications, and ferroptosis in PDAC and shed light on potential avenues for targeted interventions that modulate cancer stemness and chemosensitivity, offering prospects for improved therapeutic strategies for PDAC.

Bioluminescence Imaging of Potassium Ion Using a Sensory Luciferin and an Engineered Luciferase.

Bioluminescent indicators are power tools for studying dynamic biological processes. In this study, we present the generation of novel bioluminescent indicators by modifying the luciferin molecule with an analyte-binding moiety. Specifically, we have successfully developed the first bioluminescent indicator for potassium ions (K+), which are critical electrolytes in biological systems. Our approach involved the design and synthesis of a K+-binding luciferin named potassiorin. Additionally, we engineered a luciferase enzyme called BRIPO (bioluminescent red indicator for potassium) to work synergistically with potassiorin, resulting in optimized K+-dependent bioluminescence responses. Through extensive validation in cell lines, primary neurons, and live mice, we demonstrated the efficacy of this new tool for detecting K+. Our research demonstrates an innovative concept of incorporating sensory moieties into luciferins to modulate luciferase activity. This approach has great potential for developing a wide range of bioluminescent indicators, advancing bioluminescence imaging (BLI), and enabling the study of various analytes in biological systems.

ATP-Independent Water-Soluble Luciferins Enable Non-Invasive High-Speed Video-Rate Bioluminescence Imaging of Mice.

NanoLuc luciferase and its derivatives are attractive bioluminescent reporters recognized for their efficient photon production and ATP independence. However, utilizing them for in vivo imaging poses notable challenges. Low substrate solubility has been a prominent problem, limiting in vivo brightness, while substrate instability hampers consistent results and handling. To address these issues, we developed a range of caged PEGylated luciferins with improved stability and water solubility of up to 25 mM, resulting in substantial bioluminescence increases in mouse models. This advancement has created the brightest and most sensitive luciferase-luciferin combination, enabling high-speed video-rate imaging of freely moving mice with brain-expressed luciferase. Furthermore, we developed a bioluminescent Ca 2+ indicator with exceptional sensitivity to physiological Ca 2+ changes and paired it with a new substrate to showcase non-invasive, video-rate imaging of Ca 2+ activity in a defined brain region in awake mice. These innovative substrates and the Ca 2+ indicator are poised to become invaluable resources for biological and biomedical fields.

Preoperative pancreatic stent placement before the enucleation of insulinoma located in the head and neck of the pancreas in proximity to the main pancreatic duct: study protocol for a multicentre randomised clinical trial in Chinese tertiary medical centres.

INTRODUCTION: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests. ETHICS AND DISSEMINATION: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05523778.

Treatment of abdominal pain due to deficiency syndrome of the spleen and stomach with Bian stone plus TCM iontophoresis: A case report.

RATIONALE: Bian stone ironing and rubbing traditional Chinese medicine penetration method is based on the theory of regulating the middle and restoring balance. By using Bian stone to heat, ironing, and rubbing, pushing and rubbing in the epigastric area can regulate the spleen and stomach, restore the normal function of the middle jiao qi movement and the functions of the five organs. Bian stone hot ironing can harmonize stomach qi, nourish qi and assist yang, clear the internal organs and clear turbidity, regulate intestinal qi circulation, and promote qi stagnation. PATIENT CONCERNS: The VAS score for stomach pain is 6 points, and the SAS score is moderate anxiety, which seriously affects sleep and daily life. DIAGNOSES: epigastric pain, spleen, and stomach deficiency cold syndrome. INTERVENTIONS: Easy to digest diet, Western medicine provides famotidine acid inhibiting and protecting gastric mucosa, and mosapride promoting gastrointestinal peristalsis medication treatment; Traditional Chinese Medicine provides oral administration of Huangqi Jianzhong Tang and traditional Chinese medicine techniques such as Bianchi Ironing and Moxibustion for treatment. OUTCOMES: The patient's symptoms of stomach pain have significantly improved, with a decrease in the epigastric pain score to 0, improved anxiety, reduced fatigue, improved sleep, improved epigastric fullness, unobstructed bowel movements, and improved quality of life. The patient is very satisfied. LESSONS: The method of using Bian stone ironing and rubbing traditional Chinese medicine to treat stomach pain caused by the spleen and stomach deficiency cold can alleviate the symptoms of stomach pain in patients, and the improvement of symptoms shows a gradual increase, with significant effects. At the same time, it significantly improves patient anxiety and fatigue symptoms and can increase the sample size in future work to further clarify its clinical effects.

Bioluminescence Imaging of Potassium Ion Using a Sensory Luciferin and an Engineered Luciferase.

Bioluminescent indicators are power tools for studying dynamic biological processes. In this study, we present the generation of novel bioluminescent indicators by modifying the luciferin molecule with an analyte-binding moiety. Specifically, we have successfully developed the first bioluminescent indicator for potassium ions (K+), which are critical electrolytes in biological systems. Our approach involved the design and synthesis of a K+-binding luciferin named potassiorin. Additionally, we engineered a luciferase enzyme called BRIPO (bioluminescent red indicator for potassium) to work synergistically with potassiorin, resulting in optimized K+-dependent bioluminescence responses. Through extensive validation in cell lines, primary neurons, and live mice, we demonstrated the efficacy of this new tool for detecting K+. Our research demonstrates an innovative concept of incorporating sensory moieties into luciferins to modulate luciferase activity. This approach has great potential for developing a wide range of bioluminescent indicators, advancing bioluminescence imaging (BLI), and enabling the study of various analytes in biological systems.

Effects of soaking glutinous sorghum grains on physicochemical properties of starch.

Glutinous sorghum grains were soaked (60-80 °C, 2-8 h) to explore the effects of soaking, an essential step in industrial processing of brewing, on starch. As the soaking temperature increased, the peak viscosity and crystallinity of starch gradually decreased, while the enzymatic hydrolysis rate and storage modulus first increased and then decreased. At 70 °C, the content of amylose, the enzymatic hydrolysis rate of starch, and the final viscosity first increase and then decrease with the increase of soaking time, reaching their maximum at 6 h, increased by 53.1 %, 11.0 %, and 10.4 %, respectively, as compared with the non-soaked sample. At 80 °C (4 h), the laser confocal microscopy images showed a network structure formed between the denatured protein chains and the leached-out amylose chains. The molecular weights of starch before and after soaking were all in the range of 3.82-8.98 × 107 g/mol. Since 70 °C is lower than that of starch gelatinization and protein denaturation, when soaking for 6 h, the enzymatic hydrolysis rate of starch is the highest, and the growth of miscellaneous bacteria is inhibited, which is beneficial for subsequent processing technology. The result provides a theoretical basis for the intelligent control of glutinous sorghum brewing.

Preparation of nitrogen doped hyper-crosslinked polymer-based hard carbon for high performance Li+/Na+ battery anode.

Hyper cross-linked polymers (HCPs), as a key precursor of hard carbon (HC) anode materials, stand out because of their capacity for molecular-scale structural design and comparatively straightforward preparation techniques, which are not seen in other porous materials synthesized procedure. A novel synthesis method of HCPs is developed in this paper, which is through the incorporation of functional macromolecules, the structural control and heteroatom doping of the product has been achieved, thus augmenting its electrochemical performance in batteries. In this work, carbonized tetraphenylporphyrin zinc (TPP-Zn) doped HCP-based hard carbon (CTHCP) with stable structure was prepared by Friedel-Crafts reaction and carbonization by using naphthalene and trace TPP-Zn as monomers, dimethoxybenzene (DMB) as crosslinking agent and FeCl3 as catalyst. The introduction of TPP-Zn, a functional macromolecule with unique two-dimensional structure, realized the pore structure regulation and N doping of the raw carbonized HCP-based hard carbon (CHCP). The results showed that CTHCP had higher mesoporous volume, N content and wider layer spacing than CHCP. In addition, CTHCP anode exhibited excellent Li+/Na+ storage performance, initial reversible capacity, rate performance and long cycle life. More amount of N-containing (N-5) active sites and mesoporous content in CTHCP anode was the main reason for the improvement of Na+ storage effect. While the increased interlayer spacing had a greater effect on the lithium storage capacity. This study uncovered the design rules of HC anode materials suitable for Li+/Na+ batteries and provided a new idea for the preparation of high-performance HC anode materials.

Engineering and Characterization of 3-Aminotyrosine-Derived Red Fluorescent Variants of Circularly Permutated Green Fluorescent Protein.

Introducing 3-aminotyrosine (aY), a noncanonical amino acid (ncAA), into green fluorescent protein (GFP)-like chromophores shows promise for achieving red-shifted fluorescence. However, inconsistent results, including undesired green fluorescent species, hinder the effectiveness of this approach. In this study, we optimized expression conditions for an aY-derived cpGFP (aY-cpGFP). Key factors like rich culture media and oxygen restriction pre- and post-induction enabled high-yield, high-purity production of the red-shifted protein. We also engineered two variants of aY-cpGFP with enhanced brightness by mutating a few amino acid residues surrounding the chromophore. We further investigated the sensitivity of the aY-derived protein to metal ions, reactive oxygen species (ROS), and reactive nitrogen species (RNS). Incorporating aY into cpGFP had minimal impact on metal ion reactivity but increased the response to RNS. Expanding on these findings, we examined aY-cpGFP expression in mammalian cells and found that reductants in the culture media significantly increased the red-emitting product. Our study indicates that optimizing expression conditions to promote a reduced cellular state proved effective in producing the desired red-emitting product in both E. coli and mammalian cells, while targeted mutagenesis-based protein engineering can further enhance brightness and increase method robustness.

Genetic Characteristics of Wuxiang Virus in Shanxi Province, China.

Wuxiang virus (WUXV) is the first sandfly-borne Phlebovirus isolated from Phlebotomus chinensis collected in China and has been established as a consistent viral presence in the local sandfly populations of both Wuxiang County and Yangquan City. However, its distribution in the Shanxi Province remains unclear. In this study, three novel WUXV strains were isolated from sandflies collected from Jiexiu City, Shanxi Province, China, in 2022. Subsequently, whole-genome sequences of these novel strains were generated using next-generation sequencing. The open reading frame (ORF) sequences of the WUXV strains from the three locations were subjected to gene analysis. Phylogenetic analysis revealed that WUXV belongs to two distinct clades with geographical differences. Strains from Wuxiang County and Yangquan City belonged to clade 1, whereas strains from Jiexiu City belonged to clade 2. Reassortment and recombination analyses indicated no gene reassortment or recombination between the two clades. However, four reassortments or recombination events could be detected in clade 1 strains. By aligning the amino acid sequences, eighty-seven mutation sites were identified between the two clades, with seventeen, sixty, nine, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Additionally, selection pressure analysis identified 17 positively selected sites across the entire genome of WUXV, with two, thirteen, one, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Notably, sites M-312 and M-340 in the M segment not only represented mutation sites but also showed positive selective pressure effects. These findings highlight the need for continuous nationwide surveillance of WUXV.

Adsorption performance of mineral-carbon adsorbents derived from coal gasification fine ash: Prepared via low-temperature alkali fusion method.

To address the solid waste challenges associated with coal gasification fine ash, this study conducted a low-temperature alkali fusion de-ashing treatment to transform coal gasification fine ash into mineral-carbon adsorbent. The preparation process was simplified without grinding, carbonization and high-temperature (500-800 °C) activation treatment. The results demonstrate a positive linear correlation between the ash removal rate of the samples (measured during the preparation process, i.e., low-temperature alkaline fusion treatment of coal gasification fine ash) and their maximum equilibrium adsorption capacity for methylene blue. For the samples with an ash removal rate of 95.71 %, which exhibit a maximum adsorption capacity of 161.36 mg/g for methylene blue. The adsorption behavior of methylene blue on mineral-carbon adsorbent was a monolayer adsorption on the surface of homogeneous medium, involving both physical and chemical adsorption. The main adsorb rate-controlling steps for the samples with ash removal rates of 27.91-59.33 % and 95.71 % were the intra particle diffusion process and the liquid film diffusion process, respectively. The adsorption mechanism of methylene blue on the surface of mineral-carbon adsorbent involved electrostatic attraction and hydrogen bonding. The aforementioned results demonstrated the potential of coal gasification fine ash as an adsorbent material, providing new options for promoting the resource utilization and high-value applications of coal gasification fine ash.

Single-cell transcriptome profiling of primary tumors and paired organoids of pancreatobiliary cancer.

Single-cell RNA-seq (scRNA-seq) and cancer organoid model have shown promise in investigating tumor microenvironment heterogeneity and facilitating chemotherapeutic drug testing to inform treatment selection. It is still unknown whether the scRNA-seq results based on organoid can faithfully reflect the heterogeneity of primary pancreatobiliary cancer. To reveal the similarities and differences between primary tumors and their matched organoids at transcriptome level, we conducted scRNA-seq for paired primary tumors and organoids from one cholangiocarcinoma (CCA) and two pancreatic ductal adenocarcinoma (PDAC) patients. We identified inter-patient and intra-tumor heterogeneity and found that the organoids retained copy number variation (CNV) patterns of primary tumors. There was no significant difference in cancer stem cell (CSC) properties between the primary tumors and the organoids, whereas organoid from one PDAC case had increased mesenchymal-score and decreased epithelial-score compared with the primary tumors. All organoids showed a transition tendency from the classical subtype to the basal-like subtype in the transcriptional level. Organoids and primary tumors differed in metabolic and unfolded protein response (UPR) signatures. In addition, we revealed the heterogeneity of cancer associated fibroblasts (CAFs) and T cells, and explored the developmental trajectory of T cells. Our findings facilitate further understanding of organoid model and confirm its application prospects in pancreatobiliary cancer.

Event-related alpha power in early stage of facial expression processing in social anxiety: Influence of language context.

Accurate interpretation of the emotional information conveyed by others' facial expressions is crucial for social interactions. Event-related alpha power, measured by time-frequency analysis, is a frequently used EEG index of emotional information processing. However, it is still unclear how event-related alpha power varies in emotional information processing in social anxiety groups. In the present study, we recorded event-related potentials (ERPs) while participants from the social anxiety and healthy control groups viewed facial expressions (angry, happy, neutral) preceded by contextual sentences conveying either a positive or negative evaluation of the subject. The impact of context on facial expression processing in both groups of participants was explored by assessing behavioral ratings and event-related alpha power (0-200 ms after expression presentation). In comparison to the healthy control group, the social anxiety group exhibited significantly lower occipital alpha power in response to angry facial expressions in negative contexts and neutral facial expressions in positive contexts. The influence of language context on facial expression processing in individuals with social anxiety may occur at an early stage of processing.

Machine learning algorithm integrates bulk and single-cell transcriptome sequencing to reveal immune-related personalized therapy prediction features for pancreatic cancer.

Pancreatic cancer (PC) is a digestive malignancy with worse overall survival. Tumor immune environment (TIME) alters the progression and proliferation of various solid tumors. Hence, we aimed to detect the TIME-related classifier to facilitate the personalized treatment of PC. Based on the 1612 immune-related genes (IRGs), we classified patients into Immune_rich and Immune_desert subgroups via consensus clustering. Patients in distinct subtypes exhibited a difference in sensitivity to immune checkpoint blockers (ICB). Next, the immune-related signature (IRS) model was established based on 8 IRGs (SYT12, TNNT1, TRIM46, SMPD3, ANLN, AFF3, CXCL9 and RP1L1) and validated its predictive efficiency in multiple cohorts. RT-qPCR experiments demonstrated the differential expression of 8 IRGs between tumor and normal cell lines. Patients who gained lower IRS score tended to be more sensitive to chemotherapy and immunotherapy, and obtained better overall survival compared to those with higher IRS scores. Moreover, scRNA-seq analysis revealed that fibroblast and ductal cells might affect malignant tumor cells via MIF-(CD74+CD44) and SPP1-CD44 axis. Eventually, we identified eight therapeutic targets and one agent for IRS high patients. Our study screened out the specific regulation pattern of TIME in PC, and shed light on the precise treatment of PC.

Single-cell RNA-seq reveals characteristics in tumor microenvironment of PDAC with MSI-H following neoadjuvant chemotherapy with anti-PD-1 therapy.

Accumulating evidence suggests the minority of patients with advanced pancreatic ductal adenocarcinoma (PDAC) that have microsatellite instability high (MSI-H) can benefit from immune checkpoint inhibitors (ICIs). However, the effects of ICIs on the tumor microenvironment (TME) of PDAC remain elusive. We conducted single-cell RNA-seq (scRNA-seq) analysis on a residual lesion from a MSI-H PDAC patient who received a radical operation after eight cycles of neoadjuvant treatment (nab-paclitaxel/gemcitabine plus pembrolizumab). Multiple tumor subclusters were identified in residual lesion after neoadjuvant treatment, one of which was mainly composed of cells in the S and G2M phases. This subcluster also had enriched expression of MKI67 and PCNA and cell cycle-related signatures and was thus defined as a proliferating tumor subcluster. This subcluster had higher S_score, Fatty acid_score, UPR_score, and Glycolysis_score than others. We also identified characteristics of the TME after neoadjuvant treatment by comparing the excised primary tumors form nontreated PDAC and the residual lesion. The residual lesion was characterized with activated pancreatic stellate cells (PSCs) and exhausted T cells (Tex). We compared the receptor-ligand interactions between the two groups, and found that no checkpoint receptor-ligand pairs between T cells and tumor cells were identified in the residual lesion, while there were many checkpoint receptor-ligand pairs in the nontreated primary PDAC. In conclusion, our findings revealed the characteristics of residual lesion of advanced PDAC with MSI-H upon combination treatment of chemotherapy and immunotherapy, which might provide some valuable clues for solving the puzzle of ICI in PDAC.

Sustainable preparation of high-calorific value and low-N and S energy products through the low-temperature alkali fusion of coal gasification fine ash.

Coal gasification fine ash (CGFA) is characterized by high yield, high carbon content, and difficult recovery. This results in waste of coal resources and serious environmental pollution. To address this issue, a novel green deashing process is proposed in this study to modify CGFA into deashed carbon (DAC) with a high calorific value and an ash content of less than 5% through a low-temperature alkaline fusion process. Compared with traditional alkaline fusion (which is carried out at 600-1000 °C), low-temperature alkaline fusion treatment can efficiently remove ash minerals in the temperature range of 300-450 °C, which is beneficial to the efficient recovery of residual carbon in DA, while simultaneously improving the physicochemical properties and energy characteristics of DAC, thereby improving its combustion performance. At an alkali fusion temperature of 350 °C, a NaOH:DA ratio of 4.5:1, and a reaction time of 40 min, the resulting DAC product had ash content of 2.28%, combustible material recovery (CMR) of 82.03%, higher heating value (HHV) of 31.07 MJ kg-1, and SBET of 445.43 m2 g-1. In comparison, it was found that low-temperature alkali fusion significantly improved the deashing of CGFA when compared to existing deashing technologies. These results strongly suggest that this innovative deashing method can modify CGFA into a high-calorific value and low-N and S fuel, thereby providing a cost-effective and sustainable utilization method for CGFA.

Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma.

Immune-related liver injuries are closely associated with the liver's fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital. Twenty-five patients with advanced BTC were identified. Fifteen patients (60%) experienced immune-related liver injury during ICI treatment. We also evaluated the clinical status of patients with GC in another group receiving immunotherapy. The results demonstrated that the incidence of immune-related liver injury was higher in patients with BTC than in GC cancer (p=0.040). Multivariate analysis suggested that the type of malignant tumor and baseline liver function status were high-risk factors for grade 2 and higher immune-related liver injuries. Two patients were diagnosed with immune-related cholangitis. Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxycholic acid (UDCA) therapy but are difficult to reduce to normal levels. Liver function normalized, and symptoms improved after local treatment for cholestasis (stent implantation or PTBD). We observed a higher incidence of immune-related liver injury after ICI treatment in patients with advanced BTC. Effect of baseline liver function on the incidence of liver injury associated with immunotherapy. Interventional therapy provides rapid relief from cholestasis and is an indispensable and effective approach to the treatment of immune-related cholangitis.