Successful management of camrelizumab-induced immune-checkpoint-inhibitors-related myocarditis.

INTRODUCTION: Immune checkpoint inhibitors can cause immune-related toxicity in various systems, with myocarditis being the most severe and life-threatening manifestation. This report presents a case in which myocarditis developed following administration of programmed cell death protein-1 (PD-1) inhibitors therapy. We describe the diagnosis and treatment of this patient in detail. CASE REPORT: We present the case of a 59-year-old female diagnosed with post-operative esophageal cancer and hepatic metastases. The patient underwent second-line treatment with domestically-made PD-1 inhibitor, camrelizumab, in combination with paclitaxel (albumin-bound) and carboplatin for two cycles. During the course of treatment, an electrocardiogram (ECG) revealed ST segment elevation in leads II, III, aVF, V2, V3, and V4, along with T wave changes in leads I and aVL. Laboratory examinations showed abnormal levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT). Despite the absence of clinical symptoms, the patient was routinely hospitalized three weeks later. Based on the findings from the ECG, cardiac biomarkers, echocardiography, echocardiogram, cardiac magnetic resonance, and angiography, she was diagnosed with immune-checkpoint-inhibitors-related myocarditis. MANAGEMENT AND OUTCOME: The patient received immunoglobulin (0.5 g/kg/day) and was initially given methylprednisolone (1000 mg/day). Methylprednisolone was gradually reduced to 40 mg/day in 2 weeks. During this time, the levels of biomarkers indicative of myocardial injury also exhibited a simultaneous decline. DISCUSSION: This case highlights the importance of early detection and prompt intervention, including initiating appropriate steroid therapy and discontinuing of immune checkpoint inhibitors. Such measures can effectively prevent morbidity and mortality, ultimately leading to an improved prognosis.

[The biological functions of lysine methyltransferase PR-SET7].

PR-SET7 (also named SET8 or KMT5a) is a sole lysine methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20me1) in higher eukaryotes. The abundance of PR-SET7 is dynamically mediated by the distinct E3 ubiquitin ligases in different cell cycle phases. PR-SET7 is closely related to the regulation of cell proliferation, and the H4K20me1 catalyzed by PR-SET7 has been implicated in regulating the diverse biological processes, including DNA replication, chromosome condensation and the activation of DNA replication checkpoints. Loss of PR-SET7 results in mas-sive DNA damage, cell cycle arrest and induction of apoptosis. In addition, PR-SET7 involves in regulating the transcrip-tion of several genes, such as ERa, Wnt and p53. PR-SET7 is also essential for individual development and participates in the formation of genomic imprinting. Moreover, PR-SET7 has been reported to promote tumorigenesis and metastasis, sug-gesting that PR-SET7 may be a potential target for cancer treatment. In this review, we focus on analyzing the structure of PR-SET7 and factors influencing histone modification on regulation of PR-SET7, and discuss the mechanisms by which PR-SET7 modulates cell-cycle progression, gene transcription, individual development and tumorigenesis.

[Relationship between SGRQ score and pulmonary function and its influencing factors in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the correlation and influencing factors between the St. George respiratory questionnaire (SGRQ) and lung functions in chronic obstructive pulmonary disease (COPD) patients. METHODS: Sixty-three stable COPD patients received pulmonary function tests and SGRQ. A correlation analysis of the results was performed. They were divided into two groups according to GOLD (global initiative for chronic obstructive lung disease) classification scheme, 32 patients were in stage II (moderate) and 31 in stages III and IV (severe & very severe). And the inter-group SGRQ scores were compared. According to age, they were divided into < 70 years group (n = 31) and ≥ 70 years group (n = 32). The correlations between the SGRQ score and pulmonary functions were analyzed in different age groups. Thirty-six patients willing to participate in treatment and a 3-month follow-up were randomly divided into two groups of treatment with either salmeterol/fluticasone (50 µg/500 µg) (n = 18) or salbutamol/ipratropium bromide (120 µg/21 µg) (n = 18). The post-therapeutic changes of SGRQ score and pulmonary functions were analyzed. RESULTS: There were no significant differences in SGRQ total score and all section score between two groups according to GOLD classification scheme. There were mild to moderate correlations in the < 70 years group between lung functions including FVC%, FEV(1)%, FEFMAX%, SVC% and the SGRQ score including total score, symptoms section score and activity section score. The range of correlation coefficients was -0.341 to -0.534. However, the score only had some correlation with IC% in the ≥ 70 years group. Compared with the salbutamol/ipratropium bromide treatment group, the SGRQ score of the salmeterol/fluticasone treatment group decreased significantly after therapy (P = 0.001). CONCLUSION: Influenced by age, the SGRQ score can be used to evaluate the clinical efficacy of medications in COPD patients.

Author Correction: Increased circulating ß2-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tropomyosin-1 promotes cancer cell apoptosis via the p53-mediated mitochondrial pathway in renal cell carcinoma.

Tropomyosin-1 (TPM1), a widely expressed actin-binding protein, is downregulated in many tumors and associated with cancer progression. A previous study from our group suggested that TPM1 could be involved in renal cell carcinoma (RCC) apoptosis, but the mechanisms and details remained unknown. The present study aimed to further examine the proapoptotic effects of TPM1 and investigate the underlying mechanisms in RCC cell lines. Results from cell viability, DAPI staining and apoptosis assays demonstrated that TPM1 upregulation inhibited cell proliferation and promoted cell apoptosis in both 786-O and ACHN RCC cell lines. However, TPM1 knockdown in the two RCC cell lines did not result in the opposite effects on cell proliferation or cell apoptosis. Comet assay and western blotting results demonstrated that TPM1 overexpression induced DNA damage and decreased the expression levels of the antiapoptotic factor BCL2 apoptosis regulator, while increasing the expression levels of the proapoptotic factors BCL2 associated X, Caspase-3 and p53 in 786-O and ACHN cells. The present findings suggest that TPM1 overexpression in RCC cell lines can induce tumor cell apoptosis via the p53-mediated mitochondrial pathway. Further studies are needed to fully elucidate the potential of TPM1 as a candidate for RCC targeted therapy in the future.

Increased circulating ß2-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

Smoking is a dominant risk factor for chronic obstructive pulmonary disease (COPD) and emphysema, but not every smoker develops emphysema. Immune responses in smokers vary. Some autoantibodies have been shown to contribute to the development of emphysema in smokers. ß2-adrenergic receptors (ß2-ARs) are important targets in COPD therapy. ß2-adrenergic receptor autoantibodies (ß2-AAbs), which may directly affect ß2-ARs, were shown to be increased in rats with passive-smoking-induced emphysema in our current preliminary studies. Using cigarette-smoke exposure (CS-exposure) and active-immune (via injections of ß2-AR second extracellular loop peptides) rat models, we found that CS-exposed rats showed higher serum ß2-AAb levels than control rats before alveolar airspaces became enlarged. Active-immune rats showed increased serum ß2-AAb levels, and exhibited alveolar airspace destruction. CS-exposed-active-immune treated rats showed more extensive alveolar airspace destruction than rats undergoing CS-exposure alone. In our current clinical studies, we showed that plasma ß2-AAb levels were positively correlated with the RV/TLC (residual volume/total lung capacity) ratio (r = 0.455, p < 0.001) and RV%pred (residual volume/residual volume predicted percentage, r = 0.454, p < 0.001) in 50 smokers; smokers with higher plasma ß2-AAb levels exhibited worse alveolar airspace destruction. We suggest that increased circulating ß2-AAbs are associated with smoking-related emphysema.

Fetuin-B (FETUB): a Plasma Biomarker Candidate Related to the Severity of Lung Function in COPD.

Biomarkers for the progression of lung function in COPD are currently scarce. Plasma fetuin-B (FETUB) was identified by iTRAQ-based proteomics and was verified by ELISA in another group. Information regarding acute exacerbation (AE) was collected in a one-year follow-up programme. FETUB concentrations (1652 ± 427 ng/ml) were greater in COPD patients than in controls (1237 ± 77 ng/ml). The concentrations of FETUB in GOLD II (1762 ± 427 ng/ml), III (1650 ± 375 ng/ml) and IV (1800 ± 451 ng/ml) groups were greater than those in the controls (1257 ± 414 ng/ml) and the GOLD I (1345 ± 391 ng/ml) group. ROCs indicated that FETUB distinguished COPD patients from controls (AUC 0.747, 95% CI: 0.642-0.834) and also GOLD II, III and IV from GOLD I COPD patients (AUC: 0.770, 95% CI: 0.634-0.874). The combination of FETUB and fibrinogen performed better (AUC: 0.804, 95% CI: 0.705-0.881). FETUB also predicted the occurrence of AE (AUC: 0.707, 95% CI: 0.566-0.824) or frequent AE (AUC: 0.727, 95% CI: 0.587-0.840). FETUB concentrations were negatively correlated with FEV1%pred (r = -0.446, p = 0.000) and positively correlated with RV%pred (r = 0.317, p = 0.004), RV/TLC% (r = 0.360, p = 0.004), CT emphysema% (r = 0.322, p = 0.008) and grades of lung function (r = 0.437, p = 0.000). In conclusion, FETUB is likely to assist the diagnosis and management of COPD as a complement for other markers.