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Background: Epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) mutations are a rare and heterogeneous type of non-small cell lung cancer (NSCLC), with a prevalence of approximately 1.5-2.5%. The differences between computed tomography (CT) characteristics and clinical pathology of EGFR ex20-ins mutant NSCLC patients and classical EGFR mutant ones remain to be evaluated. Method: A retrospective study of 1432 EGFR-positive patients in three medical centers was conducted to analyze the frequency and genetic features, CT characteristics, and clinical pathology data of EGFR ex20-ins mutations. Result: Among the EGFR-positive NSCLC patients, 1.75% (25/1432) had EGFR ex20-ins mutations. Compared with classical mutations, ex20-ins patients had more solid components (50%) and a lower proportion of the lepidic subtype (35.7%) in pathological subtypes, and the most common mutation type is p.V769_D770insASV (4/25). Conclusion: Although EGFR ex20-ins mutations have similarities with classical EGFR mutations, our study still finds differences between them in clinical pathology, CT characteristics, and other aspects.

Background With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. Methods The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. Results 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. Conclusion We found that glucocorticoid 1–2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.

The aim of the present study was to summarize the clinical characteristics of nocardiosis caused by Nocardia otitidiscaviarum in order to improve the knowledge of nocardiosis. A case of dissemination nocardiosis caused by N. otitidiscaviarum in an immunocompetent host is reported and the associated literature reviewed. Informed consent for publication of this case report was provided by the patient. The present patient was a young immunocompetent man suffering from disseminated nocardiosis induced by infection with N. otitidiscaviarum. Following a poor response to β-lactam antibiotic, a combination of sulfonamide with minocycline was administered, which successfully ameliorated the symptoms. Previous studies published in English were retrieved from PubMed with ‘Nocardia otitidiscaviarum’ used as the search keyword. A total of 23 articles were retrieved from the PubMed database, supporting the assertion that N. otitidiscaviarum is a rare Nocardia species. Among these 23 cases, there were 11 cases of lymphocutaneous (48%), 5 of pulmonary (22%), 2 of brain (9%) and 1 of pyothorax (4%) infection, and 4 cases of disseminated infections (17%). Analysis of the immune state of these patients demonstrated that 9 were immunocompetent (39%), 7 of whom had cutaneous infections (30%) with a predominant history of trauma (6/7), and 14 were immunosuppressed, 9 of whom were treated with prednisolone. Microbiology and histopathology were necessary in all cases for definite diagnosis. Among the 13 cases who underwent drug susceptibility testing, 10 cases were sensitive to trimethoprim-sulfamethoxazole (TMP-SMX) and 12 cases were sensitive to aminoglycoside. In conclusion, although N. otitidiscaviarum is one of the less commonly isolated species of Nocardia, it is capable of inducing localized or disseminated infection, even in an immunocompetent host. The majority of cases respond well to TMP-SMX and aminoglycoside, but the therapeutic action of cephalosporin is weak. Identification of bacteria and drug sensitivity tests for Nocardia is critical for guiding clinical treatment.

BACKGROUND Reticulocalbin 3 (RCN3), a member of CREC (Cab45/reticulocalbin/ ERC-45/calumenin) family protein, is located in the secretory pathway of endoplasmic reticulum (ER) of living cells. Disruption of RCN3 leads to failure of lung function in the mouse model. Although ER stress has been associated with the development of a variety of tumors, the role of RCN3 in development of non-small cell lung cancer (NSCLC) in human is unknown at present. METHODS In this study a total of 41 paired NSCLC specimens (cancer group) and the adjacent normal tissues (control group) were obtained from patients undergoing lung lobectomy or pneumonectomy surgeries in Beijing Shijitan Hospital, Capital Medical University. The RCN3 mRNA and protein level in each clinical sample was determined using quantitative real time-PCR and immunoblotting, respectively. Immunohistochemistry analysis was utilized to compare the protein expressional patterns of RCN3 between the two clinical sample groups. RESULTS Immunoblotting showed that levels of RCN3 protein in the NSCLC tissues were significantly lower than those in the control group (p < 0.001), suggesting ER stress is closely associated with the cancer cells. Accordingly, the ER stress protein GRP78 (glucose-regulated protein 78, also known as BIP) was remarkably upregulated in the cancer group (p < 0.05). Within the cancer group, a significant difference in RCN3 protein expression was observed in squamous cell carcinoma versus adenocarcinoma (p < 0.05). In the lung cancer group, however, RCN3 protein levels were not correlated with the age and the gender. In addition, RCN3 mRNA levels showed no significant difference between the cancer and the control groups, suggesting that the differential regulation of RCN3 is likely at post-transcription stage in NSCLC. CONCLUSIONS Our study showed that RCN3 protein level was significantly down regulated in NSCLC, suggesting a potential correlation between RCN3 protein depletion and development of NSCLC. Although the exact cause-effect relationship between RCN3 and NSCLC needs to be further investigated, the study helps to shed additional lights on the molecular regulation of the lung cancer.

Background Kanglaite (KLT) can enhance the cytotoxic effects of chemotherapy; however, the underlying mechanism remains unclear. We investigated the mechanism underlying the cytotoxic synergy between KLT and pemetrexed in NSCLC cell lines. Methods A549 and H1975 cell lines were treated with pemetrexed and/or KLT in vitro. IC50 values, the combination index, cell cycle distribution, and signaling pathway analysis were assessed. Results Cytotoxic interactions between KLT and pemetrexed were dose-dependent in A549 and H1975 NSCLC cell lines. The administration of pemetrexed followed by KLT had a synergistic effect and an advantage over KLT followed by pemetrexed. Concomitant administration in both cell lines indicated that the cytotoxic interactions between KLT and pemetrexed were schedule-dependent. Cell cycle analysis showed that KLT arrested cells mainly in the G2/M phase, whereas pemetrexed arrested cells mainly in the S phase. Exposure to KLT first induced G2/M arrest and subsequently prevented the cytotoxicity of the S phase-specific drug pemetrexed. Signaling pathway analysis showed that exposure to pemetrexed resulted in increased phospho-p44/42MAPK levels which were inhibited by subsequent exposure to KLT. Thus pemetrexed followed by KLT inhibited the MAPK signaling pathway more obviously than KLT followed by pemetrexed. Conclusions Pemetrexed followed by KLT had a synergistic effect and an advantage over other sequences in NSCLC cell lines. The synergistic mechanism was due to KLT subsequently inhibiting the pemetrexed-activated MAPK signaling pathway. These findings may provide molecular evidence to support clinical treatment strategies for patients with NSCLC.