1.Clinicopathological features of immune checkpoint inhibitor induced myocarditis
Yan XIONG ; Dong LI ; Jiting DI ; Cuiyan GUO ; Pengkang HE ; Kai ZHAO
Chinese Journal of Pathology 2023;52(3):268-273
Objective:To investigate the clinicopathological characteristics and possible pathogenesis of immune checkpoint inhibitor (ICI) induced myocarditis, and to improve understanding of this new type of myocarditis.Methods:Two cases of ICI induced myocarditis with endomyocardial biopsy available for review were selected from the cases with immune-related adverse events treated by ICI in Peking University First Hospital, Beijing, China from 2020 to 2022. The clinical data, histomorphological characteristics, PD-L1 expression of cardiomyocytes, and classification of inflammatory cells in two cases of ICI-induced myocarditis were analyzed. Relevant literature was reviewed.Results:Case 1 was a 64-year-old male diagnosed with gastric signet ring cell carcinoma. Case 2 was a 56-year-old male ad diagnosed with lung squamous cell carcinoma. Both patients developed acute myocarditis during PD-1 inhibitor treatment, and the disease progressed rapidly. Case 2 was more serious than case 1. Endomyocardial biopsy showed definite cardiomyocytic injury and prominent inflammatory infiltration in both cases, which met the full Dallas criteria for myocarditis. The degenerated and necrotic cardiomyocytes accounted for about 10% of the tissues in case 1 and 30% in case 2, respectively. In case 1, the inflammatory cells counted in the densest area were about 150/HPF, comprised of CD20 + cells (about 5/HPF), CD3 + cells (about 60/HPF), CD8 + cells (about 50/HPF) and CD68 + cells (about 70/HPF). In case 2, the inflammatory cells counted in the densest area were about 350/HPF, comprised of CD20 + cells (0/HPF), CD3 + cells (about 100/HPF), CD8 + cells (about 90/HPF) and CD68 + cells (about 200/HPF). In both cases, PD-L1 + cardiomyocytes aggregated in the inflammatory lesions, and the percentage was about 8% and 30% in case 1 and case 2, respectively. Conclusions:ICI-induced myocarditis is frequently acute onset, severe symptoms, and rapid progression. The histological morphology meets the full Dallas criteria for myocarditis. Expression of PD-L1 in cardiomyocytes can be detected in the inflammatory lesions. The inflammatory cells are comprised of CD8 + T lymphocytes and macrophages and the number of macrophages significantly exceeds that of lymphocytes. Combined with the pathological characteristics and the history of ICI treatment, the diagnosis of ICI-induced myocarditis can be made.
2.Role of Oxidative Stress in Ulcerative Colitis and Traditional Chinese Medicine Prevention and Treatment: A Review
Bo CHEN ; Xitong SUN ; Xinqian DONG ; Wei WANG ; Hongquan SONG ; Jiting ZHAO ; Ya ZHENG ; Honghao ZHANG ; Qingxin LUAN ; Kangning ZHAO ; Hualiang DENG ; Zhen SUN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):264-273
Ulcerative colitis (UC) is a commonly seen digestive system disease with unclear pathogenesis. The condition is complex and variable, often chronic, and has a long treatment period with no specific cure. Currently, the treatment of UC often involves the use of corticosteroids, aminosalicylates, and biologics in western medicine, which provide fast-acting and definite efficacy in the short term. However, with prolonged medication, some patients may develop drug resistance and worsening of the disease, leading to the occurrence of colon cancer. Research has found that oxidative stress is one of the important pathogenic factors in UC and influences its onset and development. Oxidative stress is a state of imbalance between oxidative products and the antioxidant system in the body, characterized by overexpression of oxidative products such as malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), or deficiency of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). It is worth noting that traditional Chinese medicine (TCM), as a unique characteristic medicine of China, has achieved significant efficacy in the treatment of UC. Studies have shown that TCM effectively inhibits the occurrence of UC by suppressing the accumulation of metabolites and antagonizes the development of UC by enhancing the antioxidant system. Therefore, using TCM to regulate the oxidative balance as a diagnostic and therapeutic approach may be a new method and direction for the treatment of UC in the future. Based on the above research, this article summarized the mechanisms of key pathogenic proteins in oxidative stress and the occurrence and development of UC, and compiled the effective ingredients of Chinese medicine, single drugs, prescriptions, and acupuncture and moxibustion in regulating upstream and downstream target proteins of oxidative stress. These interventions can reduce pathological damage to the intestinal mucosa, lower the colon injury index, enrich the intestinal microbiota, increase colon length, and improve clinical symptoms of UC. The article is expected to expand the application of TCM in the treatment of UC and provide a reliable scientific theoretical basis.
3.Modeling hepatoblastoma development with human fetal liver organoids reveals YAP1 activation is sufficient for tumorigenesis.
Li YANG ; Jin CHEN ; Jianqing LIANG ; Yufeng ZHANG ; Qingzhe WANG ; Xiaojun REN ; Jinsong WEI ; Qianchun GONG ; Jiting ZHANG ; Ning JIANG ; Xinhua LIN ; Jin LI ; Bing ZHAO
Protein & Cell 2022;13(9):683-688