IL-33 released during challenge phase regulates allergic asthma in an age-dependent way.

Epithelial-derived cytokines, especially type 2 alarmins (TSLP, IL-25, and IL-33), have emerged as critical mediators of type 2 inflammation. IL-33 attracts more interest for its strong association with allergic asthma, especially in childhood asthma. However, the age-dependent role of IL-33 to the development of allergic asthma remains elusive. Here, using OVA-induced allergic asthma model in neonatal and adult mice, we report that IL-33 is the most important alarmin in neonatal lung both at steady state or inflammation. The deficiency of IL-33/ST2 abrogated the development of allergic asthma only in neonates, whereas in adults the effect was limited. Interestingly, the deficiency of IL-33/ST2 equally dampened the ILC2 responses in both neonatal and adult models. However, the effect of IL-33/ST2 deficiency on Th2 responses is age-dependent, which is only blocked in neonates. Furthermore, IL-33/ST2 signaling is dispensable for OVA sensitization. Following OVA challenge in adults, the deficiency of IL-33/ST2 results in compensational more TSLP, which in turn recruits and activates lung DCs and boosts Th2 responses. The enriched γδ T17 cells in IL-33/ST2 deficient neonatal lung suppress the expression of type 2 alarmins, CCL20 and GM-CSF via IL-17A, thus might confer the inhibition of allergic asthma. Finally, on the basis of IL-33 deficiency, the additive protective effects of TSLP blocking is much more pronounced than IL-25 blocking in adults. Our studies demonstrate that the role of IL-33 for ILC2 and Th2 responses varies among ages in OVA models and indicate that the factor of age should be considered for intervention of asthma.

Neutrophil-to-lymphocyte ratio and prognostic nutritional index in predicting composite endpoint of early safety following transcatheter aortic valve replacement.

BACKGROUND: The incidence of composite endpoint of early safety (CEES) after transcatheter aortic valve replacement (TAVR) has been a topic of focus within the cardiovascular field due to its impact on long-term patient outcomes. Timely prophylactic interventions are crucial for patients identified as high risk for CEES through preoperative risk stratification. OBJECTIVES: This study aimed to explore the connection between inflammatory and nutritional markers, specifically the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI), and CEES occurrence. MATERIAL AND METHODS: A cohort of 134 patients undergoing TAVR in a single center was studied. The study endpoint was the occurrence of CEES, which was defined according to the Valve Academic Research Consortium 3. RESULTS: The CEES was reached in 25.4% of patients at 30 days. A high NLR was associated with a 5.55-fold increased risk of CEES (95% confidence interval (95% CI): 1.52-20.29; p < 0.05), while a low PNI was linked to a 4.43-fold increased risk (95% CI: 1.55-12.65; p < 0.01). Combining NLR and PNI provided additional risk stratification for high-risk patients (hazard ratio (HR), 95% CI: 2.24-43.37; p < 0.005). CONCLUSIONS: A high NLR and low PNI were shown to be significant predictors of CEES following TAVR. These findings underscore the significance of NLR and PNI in the risk assessment of TAVR patients, offering valuable insights for preventive measures.

Enhancing Lithium-Ion Battery Health Predictions by Hybrid-Grained Graph Modeling.

Predicting the health status of lithium-ion batteries is crucial for ensuring safety. The prediction process typically requires inputting multiple time series, which exhibit temporal dependencies. Existing methods for health status prediction fail to uncover both coarse-grained and fine-grained temporal dependencies between these series. Coarse-grained analysis often overlooks minor fluctuations in the data, while fine-grained analysis can be overly complex and prone to overfitting, negatively impacting the accuracy of battery health predictions. To address these issues, this study developed a Hybrid-grained Evolving Aware Graph (HEAG) model for enhanced prediction of lithium-ion battery health. In this approach, the Fine-grained Dependency Graph (FDG) helps us model the dependencies between different sequences at individual time points, and the Coarse-grained Dependency Graph (CDG) is used for capturing the patterns and magnitudes of changes across time series. The effectiveness of the proposed method was evaluated using two datasets. Experimental results demonstrate that our approach outperforms all baseline methods, and the efficacy of each component within the HEAG model is validated through the ablation study.

Advances in Synthesis and Applications of Single-Atom Catalysts for Metal Oxide-Based Gas Sensors.

As a stable, low-cost, environment-friendly, and gas-sensitive material, semiconductor metal oxides have been widely used for gas sensing. In the past few years, single-atom catalysts (SACs) have gained increasing attention in the field of gas sensing with the advantages of maximized atomic utilization and unique electronic and chemical properties and have successfully been applied to enhance the detection sensitivity and selectivity of metal oxide gas sensors. However, the application of SACs in gas sensors is still in its infancy. Herein, we critically review the recent advances and current status of single-atom catalysts in metal oxide gas sensors, providing some suggestions for the development of this field. The synthesis methods and characterization techniques of SAC-modified metal oxides are summarized. The interactions between SACs and metal oxides are crucial for the stable loading of single-atom catalysts and for improving gas-sensitive performance. Then, the current application progress of various SACs (Au, Pt, Cu, Ni, etc.) in metal oxide gas sensors is introduced. Finally, the challenges and perspectives of SACs in metal oxide gas sensors are presented.

In-depth human immune cellular profiling from newborn to frail.

Immune functional decline and remodeling accompany aging and frailty. It is still largely unknown how changes in the immune cellular composition differentiate healthy individuals from those become frail at a relatively early age. Our aim in this exploratory study was to investigate immunological changes from newborn to frailty, and the association between health statute and various immune cell subtypes. The participants analyzed in this study covered human cord blood cells and peripheral blood cells collected from young adults, healthy and frail old individuals. A total of 30 immune cell subsets was performed by flow cytometry based on the surface markers of immune cells. Furthermore, frailty was investigated for its relations with various leukocyte subpopulations. Frail individuals exhibited a higher CD4/CD8 ratio, a higher proportion of CD4+ central memory T (TCM) cells, CD8+ effector memory T cells, CD27- switched memory B (CD27-BSM) cells, CD27+ switched memory B cells, age-associated B cells (ABCs) and CD38-CD24- B cells, and a lower proportion of naïve CD8 + T cells and progenitor B cells. The Frailty index score was found to be associated with naïve T cells, CD4/CD8 ratio, ABCs, CD27-BSM cells, and CD4+ TCM cells. Our findings conducted a relatively comprehensive and extensive atlas of age- and frailty-related changes in peripheral leukocyte subpopulations from newborn to frailty. The immune phenotypes identified in this study can contribute to a deeper understanding of immunosenescence in frailty and may provide a rationale for future interventions and diagnosis.

Pulsatile flow increases METTL14-induced m 6 A modification and attenuates septic cardiomyopathy: an experimental study.

INTRODUCTION: Septic cardiomyopathy is a sepsis-mediated cardiovascular complication with severe microcirculatory malperfusion. Emerging evidence has highlighted the protective effects of pulsatile flow in case of microcirculatory disturbance, yet the underlying mechanisms are still elusive. The objective of this study was to investigate the mechanisms of N 6 -methyladenosine (m 6 A) modification in the alleviation of septic cardiomyopathy associated with extracorporeal membrane oxygenation (ECMO)-generated pulsatile flow. METHODS: Rat model with septic cardiomyopathy was established and was supported under ECMO either with pulsatile or non-pulsatile flow. Peripheral perfusion index (PPI) and cardiac function parameters were measured using ultrasonography. Dot blot assay was applied to examine the m 6 A level, while qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry were used to measure the expressions of related genes. RNA immunoprecipitation assay was performed to validate the interaction between molecules. RESULTS: The ECMO-generated pulsatile flow significantly elevates microcirculatory PPI, improves myocardial function, protects the endothelium, and prolongs survival in rat models with septic cardiomyopathy. The pulsatile flow mediates the METTL14-mediated m 6 A modification to zonula occludens-1 (ZO-1) mRNA (messenger RNA), which stabilizes the ZO-1 mRNA depending on the presence of YTHDF2. The pulsatile flow suppresses the PI3K-Akt signaling pathway, of which the downstream molecule Foxo1, a negative transcription factor of METTL14, binds to the METTL14 promoter and inhibits the METTL14-induced m 6 A modification. CONCLUSION: The ECMO-generated pulsatile flow increases METTL14-induced m 6 A modification in ZO-1 and attenuates the progression of septic cardiomyopathy, suggesting that pulsatility might be a new therapeutic strategy in septic cardiomyopathy by alleviating microcirculatory disturbance.

Association between Weight-Adjusted Waist Index and depressive symptoms: A nationally representative cross-sectional study from NHANES 2005 to 2018.

BACKGROUND: Depressive symptoms are strongly associated with the development of various diseases and are one of the leading causes of disability in the world. However, the relationship between weight-adjusted waist index (WWI) and depressive symptoms has not been studied. This study aimed to assess the relationship between depressive symptoms and WWI. METHODS: This study took NHANES data from 2005 to 2018 with 32,374 participants. Depressive symptoms were measured by a questionnaire (PHQ-9).WWI was determined by dividing the square root of waist circumference (cm) by weight (kg). Multivariate logistic regression models, smoothed curve fitting, and weighted generalized additive model (GAM) regression were used to examine the relationship between depressive symptoms and WWI, BMI, and waist circumference. Subgroup analyses and interaction tests were also performed. RESULTS: In fully adjusted models, the OR (95 % CI) for WWI and depressive symptoms with WWI, BMI, and waist circumference were 1.18 (1.05, 1.34), BMI 1.01 (1.00, 1.02, 1.01 (1.00, 1.01), respectively. Participants in the highest quartile (Q4) had a 49 % higher depressive symptoms compared to those in the lowest quartile (Q1) (OR = 1.49, 95 % CI:1.14-1.96). Subgroup analyses and interaction tests showed a stable relationship between depressive symptoms and WWI. LIMITATIONS: It is difficult to determine a causal relationship between the two; questionnaire collection may be somewhat biased; CONCLUSIONS: WWI was positively associated with depressive symptoms. This association was stronger than BMI and waist circumference. However, this relationship was stable. This study emphasizes the potential utility of WWI in preventing depressive symptoms and improving prognosis in the population.

Progress of epigenetic modification of SATB2 gene in the pathogenesis of non-syndromic cleft lip and palate.

Non-syndromic Cleft Lip and Palate (NSCLP) is one of the most common congenital craniofacial malformations. However, there is no enough knowledge about its mechanism, even through many relevant studies verify that cleft lip and palate is caused by interactions between environmental and genetic factors. SATB2 gene is one of the most common candidate genes of NSCLP, and the development of epigenetics provides a new direction on pathogenesis of cleft lip and palate. This review summarizes SATB2 gene in the pathogenesis of non-syndromic cleft lip and palate, expecting to provide strategies to prevent and treat cleft and palate in the future.

Primary or metastatic branchial cleft carcinoma?: a case report.

The brachial cleft carcinoma is an extremely rare head and neck facial malignancy, and there is some disagreement about its differential diagnosis. In this paper, we report a 63-year-old male patient who had a mass on the left side of the neck and diagnosed as the brachial cleft carcinoma by intraoperative biopsy pathology. However, this patient was diagnosed with the carcinoma of the left soft palate more than 20 days after surgery and esophageal cancer 2 years later, and was treated accordingly. Therefore, it is hard to confirm whether the branchial cleft carcinoma is primary or metastatic. In fact, the diagnostic criteria for primary squamous cell carcinoma of branchial cleft cysts are very rigorous. Confirmation of the diagnosis is based on pathological examination of the branchial cleft cyst epithelium lined with squamous cells, meanwhile, a thorough examination should also be performed to exclude the presence of other primary cancers.

Higher weight-adjusted waist index is associated with increased likelihood of kidney stones.

Objectives: The objective of this study was to evaluate the association between weight-adjusted waist index (WWI) and the prevalence of kidney stones among adults in the United States. Methods: The cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2007-2018. A total of 31,344 participants were categorized into two groups: those with kidney stones and those without. WWI was determined by dividing waist circumference (cm) by the square root of body weight (kg). To examine the relationship between kidney stones and WWI, multivariate logistic regression models, smoothed curve fitting, and weighted generalized additive model (GAM) regression were employed. Subgroup analysis and interaction tests were conducted to explore the stability of this association across different groups. Results: The final analysis comprised a total of 31,344 participants, including 2,928 individuals who had a history of kidney stones. In the fully adjusted model, an increase in WWI exhibited a positive correlation with the prevalence of kidney stones (OR=1.34, 95% CI: 1.18-1.51). When WWI was converted into quartiles (Q1-Q4), participants in the highest quartile (Q4) had a 69% greater risk of developing kidney stones compared to those in the lowest quartile (Q1) (OR=1.69, 95% CI: 1.28-2.25). This positive association was particularly notable among non-diabetic patients. Conclusion: Our study demonstrates a significant positive association between weight-adjusted waist index levels and an elevated prevalence of kidney stones among US adults. Furthermore, this research highlights the potential utility of weight-adjusted waist index in the prevention of kidney stones in the overall population. This relationship is limited and further research is needed to test this hypothesis.

Case report: Surgical strategies of a giant thrombus from the ascending aorta to the arch.

Large mural thrombi in the relatively normal ascending aorta are extremely uncommon conditions that may lead to major adverse cardiovascular events due to new embolism. Because of their changeable variations, the management of these unstable thrombi is challenging and controversial. The size, morphology, location, embolic involvement, and patients' conditions are all crucial for therapeutic decision-making. Treatment options include anticoagulation, thrombolysis, surgical thrombectomy, and endovascular stenting. Therefore, surgical strategies should be highly individualized. Herein, we present a rare case of a huge thrombus from the ascending aorta to the arch in a 43-year-old man. Considering the high risks of catastrophic embolic events, surgical removal of the aortic mass, thromboendarterectomy, and reconstruction of the arterial wall were performed with a satisfactory outcome. This report illustrates our experience of surgical strategies and perioperative treatments for this challenging case, and contemporary surgical management for mural thrombi in the ascending aorta was also thoroughly discussed.

Progression of bilateral morning glory syndrome associated with unilateral persistent fetal vasculture: A case report of long term follow-up in an infant.

PURPOSE: To describe a case of Bilateral Morning Glory Syndrome (MGS) associated with Unilateral Persistent Fetal Vasculature (PFV) in a 3-day old neonate. OBSERVATIONS: A 3-day-old neonate was found bilateral retinal abnormalities due to neonatal eye screening. Dilated fundus exam showed bilateral optic disc dysplasia with the persistent hyaloid vessels in right eye at first. With the progress of the disease, optic disc was enlarged with central umbilication which with a similar anomalous radiating peripapillary vascular appearance, the persistent hyaloid vessels in vitreous cavity of right eye gradually disappear, a large amount of exudation can be seen in the posterior pole retina with macular movement in both eyes. Bilateral vitrectomy was performed in this case, then the condition of the neonate's both eyes is stable until 1 year old. CONCLUSIONS AND IMPORTANCE: This is a rare case that showing the development of MGS and PFV and the relationship between these two diseases. In addition, we completely observed the whole process of the change of the persistent hyaloid vessels in the vitreous cavity of a case of MGS associated with PFV.

Self-aligned patterning technique for fabricating high-performance diamond sensor arrays with nanoscale precision.

Efficient, nanoscale precision alignment of defect center creation in photonics structures in challenges the realization of high-performance photonic devices and quantum technology applications. Here, we propose a facile self-aligned patterning technique based on conventional engineering technology, with doping precision that can reach ~15 nm. We demonstrate this technique by fabricating diamond nanopillar sensor arrays with high consistency and near-optimal photon counts. The sensor array achieves high yield approaching the theoretical limit, and high efficiency for filtering sensors with different numbers of nitrogen vacancy centers. Combined with appropriate crystal orientation, the system achieves a saturated fluorescence rate of 4.34 Mcps and effective fluorescence-dependent detection sensitivity of 1800 cps-1/2 . These sensors also show enhanced spin properties in the isotope-enriched diamond. Our technique is applicable to all similar solid-state systems and could facilitate the development of parallel quantum sensing and scalable information processing.

i5hmCVec: Identifying 5-Hydroxymethylcytosine Sites of Drosophila RNA Using Sequence Feature Embeddings.

5-Hydroxymethylcytosine (5hmC), one of the most important RNA modifications, plays an important role in many biological processes. Accurately identifying RNA modification sites helps understand the function of RNA modification. In this work, we propose a computational method for identifying 5hmC-modified regions using machine learning algorithms. We applied a sequence feature embedding method based on the dna2vec algorithm to represent the RNA sequence. The results showed that the performance of our model is better that of than state-of-art methods. All dataset and source codes used in this study are available at: https://github.com/liu-h-y/5hmC_model.

Excited-State Spectroscopy of Spin Defects in Hexagonal Boron Nitride.

A negatively charged boron vacancy (VB-) color center in hexagonal boron nitride has recently been proposed as a promising quantum sensor due to its excellent properties. However, the spin level structure of the VB- color center is still unclear, especially for the excited state. Here we measured and confirmed the excited-state spin transitions of VB- using an optically detected magnetic resonance (ODMR) technique. The zero-field splitting of the excited state is 2.06 GHz, the transverse splitting is 93.1 MHz, and the g factor is 2.04. Moreover, negative peaks in fluorescence intensity and ODMR contrast at the level anticrossing point were observed, and they further confirmed that the spin transitions we measured came from the excited state. Our work deepens the understanding of the excited-state structure of VB- and promotes VB--based quantum sensing applications.

Epidermal growth factor/epidermal growth factor receptor signaling blockage inhibits tumor cell-derived exosome uptake by oral squamous cell carcinoma through macropinocytosis.

Various cell types secrete exosomes into their surrounding extracellular space, which consequently affect the function and activity of recipient cells. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. Although a variety of endocytic pathways are reportedly involved in the cellular uptake of exosomes, detailed mechanisms remain unknown. The present study demonstrated that treatment with recombinant epidermal growth factor (EGF) time- and dose-dependently promoted cellular uptake of oral squamous cell carcinoma (OSCC) cell-derived exosomes into OSCC cells themselves. Conversely, EGF receptor (EGFR) knockdown and treatment with EGFR inhibitors, including erlotinib and cetuximab, abrogated OSCC cell uptake of exosomes. The macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) blocked the effects of active EGF/EGFR signaling on uptake of OSCC cell-derived exosomes. These EGFR inhibitors also suppressed OSCC cell-derived exosome-induced proliferation, migration, invasion, stemness, and chemoresistance of OSCC cells. Taken together, the data presented herein suggest that EGFR inhibitors might inhibit the malignant potential of OSCC cells through direct inhibition of not only EGFR downstream signaling pathway but also cellular uptake of OSCC cell-derived exosomes through macropinocytosis.

Characterization of neuroendocrine regulation- and metabolism-associated molecular features and prognostic indicators with aid to clinical chemotherapy and immunotherapy of patients with pancreatic cancer.

The worldwide prevalence of pancreatic cancer has been rising in recent decades, and its prognosis has not improved much. The imbalance of substance and energy metabolism in tumour cells is among the primary causes of tumour formation and occurrence, which is often controlled by the neuroendocrine system. We applied Cox and LASSO regression analysis to develop a neuroendocrine regulation- and metabolism-related prognostic risk score model with three genes (GSK3B, IL18 and VEGFA) for pancreatic cancer. TCGA dataset served as the training and internal validation sets, and GSE28735, GSE62452 and GSE57495 were designated as external validation sets. Patients classified as the low-risk population (category, group) exhibited considerably improved survival duration in contrast with those classified as the high-risk population, as determined by the Kaplan-Meier curve. Then, we combined all the samples, and divided them into three clusters using unsupervised clustering analysis. Unsupervised clustering, t-distributed stochastic neighbor embedding (t-SNE), and principal component analysis (PCA) were further utilized to demonstrate the reliability of the prognostic model. Moreover, the risk score was shown to independently function as a predictor of pancreatic cancer in both univariate and multivariate Cox regression analyses. The results of gene set enrichment analysis (GSEA) illustrated that the low-risk population was predominantly enriched in immune-associated pathways. "ESTIMATE" algorithm, single-sample GSEA (ssGSEA) and the Tumor Immune Estimation Resource (TIMER) database showed immune infiltration ratings were enhanced in the low-risk category in contrast with the high-risk group. Tumour immune dysfunction and exclusion (TIDE) database predicted that immunotherapy for pancreatic cancer may be more successful in the high-risk than in the low-risk population. Mutation analysis illustrated a positive link between the tumour mutation burden and risk score. Drug sensitivity analysis identified 44 sensitive drugs in the high- and low-risk population. GSK3B expression was negatively correlated with Oxaliplatin, and IL18 expression was negatively correlated with Paclitaxel. Lastly, we analyzed and verified gene expression at RNA and protein levels based on GENPIA platform, HPA database and quantitative real-time PCR. In short, we developed a neuroendocrine regulation- and metabolism-associated prognostic model for pancreatic cancer that takes into account the immunological microenvironment and drug sensitivity.

EEG Emotion Recognition Applied to the Effect Analysis of Music on Emotion Changes in Psychological Healthcare.

Music therapy is increasingly being used to promote physical health. Emotion semantic recognition is more objective and provides direct awareness of the real emotional state based on electroencephalogram (EEG) signals. Therefore, we proposed a music therapy method to carry out emotion semantic matching between the EEG signal and music audio signal, which can improve the reliability of emotional judgments, and, furthermore, deeply mine the potential influence correlations between music and emotions. Our proposed EER model (EEG-based Emotion Recognition Model) could identify 20 types of emotions based on 32 EEG channels, and the average recognition accuracy was above 90% and 80%, respectively. Our proposed music-based emotion classification model (MEC model) could classify eight typical emotion types of music based on nine music feature combinations, and the average classification accuracy was above 90%. In addition, the semantic mapping was analyzed according to the influence of different music types on emotional changes from different perspectives based on the two models, and the results showed that the joy type of music video could improve fear, disgust, mania, and trust emotions into surprise or intimacy emotions, while the sad type of music video could reduce intimacy to the fear emotion.

Neonatal LPS Administered Before Sensitization Reduced the Number of Inflammatory Monocytes and Abrogated the Development of OVA-Induced Th2 Allergic Airway Inflammation.

It is becoming increasingly clear that environment factors during early life play a pivotal role in the development of allergic asthma. Among these, a traditional farm is one of the strongest protective environments, and the protective effects have been, at least in part, attributed to the high-level exposure to lipopolysaccharide (LPS) on farms. However, the underlying mechanisms remain elusive, especially in ovalbumin (OVA)-induced neonatal allergic asthma model. Here, we used the OVA-induced asthma model in two age groups, neonatal and adult, when mice were first sensitized with peritoneal OVA/alum as neonates and adults, respectively. LPS was injected in the peritoneal cavity before OVA/alum sensitization. The effects of LPS treatment on allergic airway inflammation in the lung and the immune milieu in the peritoneal cavity were determined and compared between these two age groups. We found that LPS treatment abrogated the development of Th2 allergic airway responses in the neonatal group. In the adult group, the ameliorated Th2 allergic responses were accompanied with Th17 responses and neutrophil infiltration upon LPS treatment. We further investigated the immune milieu in the peritoneal cavity to elucidate the underlying mechanisms of this age-dependent difference. Our data show that in neonatal mice, LPS treatment significantly reduced the number of inflammatory monocytes in the peritoneal cavity. In the adult group, LPS treatment shifted the function of these cells which associated with Th1 and Th17 polarization. Our results provide more evidence that immunity in early life is distinct from that in adults, especially in the peritoneal cavity, and emphasize the importance of timing for the intervention of allergic asthma. Our results suggest that LPS treatment during early life is protective for the development of Th2 allergic responses. On the other hand, it might lead to a more severe phenotype of asthma when dampening the Th2 responses in adult mice.

Pneumonitis, appendicitis, and biliary obstruction during toripalimab treatment in a patient with extensive-stage small-cell lung cancer: a case report.

In recent years, immune checkpoint inhibitors (ICIs) have become a standard treatment for patients with advanced lung cancers. With the widespread use of immunotherapy in clinical practice, immune-related adverse events (irAEs) have become increasingly common. This case report details a 72-year-old man with small-cell lung cancer (SCLC) who developed pneumonitis, appendicitis, and biliary obstruction during treatment with toripalimab. The patient was initially diagnosed with limited-stage SCLC in January 2019 and completed 5 sequential cycles of etoposide/cisplatin (EP) and radiotherapy (60 Gy/30 F). The overall response was complete response (CR) after first line treatment. He developed radiation pneumonitis after completion of radiotherapy, which responded well to symptomatic treatment. Due to newly diagnosed bone metastasis, he was administered toripalimab intravenously every 3 weeks and 12 mg anlotinib orally once a day from January 2020. By the third cycle, the patient presented with electrocardiographic abnormalities, gingival swelling and pain, and hoarseness, and consequently, the anlotinib was suspended. After 4 cycles, he developed suppurative appendicitis, which was managed successfully with anti-inflammatory agents. He then presented with shortness of breath on exertion and after a comprehensive examination, he was diagnosed with ICI-related-pneumonitis. After 6 weeks of treatment with methylprednisolone, the shortness of breath was mostly relieved and treatment continued. In June 2020, the patient developed severe vomiting. Computed tomography (CT) indicated biliary obstruction, and at endoscopic retrograde cholangiopancreatography (ERCP) there was edema of the major papilla of the duodenum. The patient's symptoms were relieved after treatment with gastric acid suppression and antiemetics. Re-examination by magnetic resonance imaging (MRI) showed that the biliary obstruction had been resolved. Although the disease progressed after immunotherapy, no tumor tissue related to the biliary obstruction was detected, and this was therefore classified as an irAE.