Pathological findings of pulmonary papillary adenoma with EGFR mutation and literature review: two cases report.

OBJECTIVE: Pulmonary papillary adenoma is an extremely rare benign tumor. It is derived from type II lung cells and club cells, suggesting that it may originate from stem cells with two-way differentiation. Only one case has been reported with FGFR2-IIIb overexpression. METHODS: Two cases of pulmonary papillary adenoma with available data on clinical features, histological morphology, immunophenotype and molecular characteristics were analyzed. RESULTS: Both tumors were well-circumscribed unencapsulated nodules composed of papillary structures with fibrovascular cores lined by a single layer of cuboidal or columnar epithelium without necrosis, nuclear atypia and mitoses, or invasion. But malignant transformation features include complex branching structures and significantly enlarged, irregular, and crowded malignant cells in one case. Immunohistochemistry showed that the tumor cells were strongly positive for TTF1, NapsinA, EMA and CK7 and negative for CEA and P63, with a low Ki-67 proliferation index. The EGFR somatic mutation exon19:c.2236_2256delinsATC (p.E746_S752delinsI) was found in one case by next-generation sequencing (NGS) technology. CONCLUSION: Pulmonary papillary adenoma is very rare. Virtually all papillary adenomas are clinically silent and discovered incidentally. They are benign tumors, and resection is curative. An EGFR 19 exon deletion mutation in a patient with this tumor type was detected for the first time by NGS, and our results suggest that the malignant transformation of pulmonary papillary adenoma may be mediated by EGFR mutation.

PYCR1 regulates TRAIL­resistance in non­small cell lung cancer cells by regulating the redistribution of death receptors.

Although recombinant human TNF-related apoptosis-inducing ligand (TRAIL) protein exhibits antitumor activity in a number of lung and liver cancer cells and tumor-bearing animals, TRAIL resistance has substantially restricted its clinical application. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a key enzyme in the regulation of proline synthesis. PYCR1 is highly expressed in various types of malignant tumor, in which it has been implicated in 5-fluorouracil resistance. However, the possible relationship between PYCR1 and TRAIL resistance remains unclear. In the present study, both reverse transcription-quantitative PCR and western blotting were performed. The results indicated that H1299 cells had higher PYCR1 expression levels and were less sensitive to TRAIL compared with the TRAIL-sensitive cell line, H460. PYCR1 knockdown in H1299 cells increased TRAIL sensitivity, increased the localization of death receptors (DRs) on the cell surface and activated Caspase-3/8. By contrast, overexpression of PYCR1 in H1299 cells decreased TRAIL sensitivity, reduced the distribution of DRs on the cell surface and suppressed the activation of Caspase-3/8. Taken together, these results suggested that PYCR1 promoted TRAIL resistance in the non-small cell lung cancer cell line, H1299, by preventing redistribution of DRs to the plasma membrane. This in turn inhibited TRAIL-mediated cell apoptosis by reducing the activation of Caspase-3/8.

Social trust and the location choices of foreign firms in China-The moderating role of formal institution and cultural distance.

The institutional environment has a significant impact on the location of overseas investments by multinational enterprises (MNEs). However, there remain two research gaps. First, fewer studies focused on the impact of subnational regional institutions on the location choices of MNEs. Second, study on informal institutions has been more limited. This study investigates the effect of the informal institution (social trust) in the Chinese subnational region on the location choices of foreign firms and the mechanism of its role. Using the sample of foreign firms' location choices in China from 2008 to 2020 in Orbis Global Enterprise Database, this study finds that social trust positively related to the location choices of foreign firms in subnational regions. Our results also show that this positive effect is contingent on the formal institution and the cultural distance between home and host country. When the formal institution is strong and the cultural distance between home and host country is high, social trust has a more significant positive impact on the location choices of foreign firms in subnational regions. Besides, the results show that cost advantage, information advantage and innovation advantage are important mechanisms for social trust to influence foreign firms' location choices in subnational regions. This study is important for understanding the role of subnational regional informal institutions in influencing strategic decisions of MNEs. At the same time, it has certain guiding significance for governments in attracting foreign direct investment and for multinational enterprises in selecting suitable overseas investment locations.

How to stimulate employees' innovative behavior: Internal social capital, workplace friendship and innovative identity.

With the digital transformation of the economy and the rise of community innovation, how stimulating employees' innovative behavior (EIB) becomes the basis for building sustainable competitive advantage in organizations. However, research has yet to systematically investigate the effect of internal social capital (ISC) on EIB. Based on social identity theory and resource conservation theory, this paper constructs a model to explain the mediating role of II between ISC and EIB and the moderating role of workplace friendship (WF). Using SPSS 27 and Amos 24 to analyze the data of 284 questionnaires, the results show that (1) ISC has a positive effect on EIB, (2) II plays a partial mediating effect in the relationship between ISC and EIB, and (3) WF has a positive moderating effect on the relationship between ISC and EIB. The conclusion provides management insight and practical guidance for creating an internal organizational climate to promote EIBs.

Sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma: A prospective, open-label, single-arm, phase II clinical study.

Objective: To evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC. Methods: This open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m2, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Results: Forty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9-65.1%) and 91.3% (95% CI: 79.2-97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2-20.2 months). The median PFS was 9.0 months (95% CI: 7.1-10.9 months). The median DoR was 10.8 months (95% CI: 4.8-16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5-84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events. Conclusion: Sintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies. Clinical Trial Registration: https://ClinicalTrials.gov, identifier NCT04411706.