Efficacy and safety analysis of anlotinib combined with PD-1 inhibitors in advanced non-small cell lung cancer: a retrospective cohort study.

Background: Programmed cell death 1 (PD-1) inhibitors are beneficial for patients with advanced lung cancer. However, the population who will benefit from PD-1 inhibitors is limited, and their efficacy needs to be further improved. Antiangiogenic agents may regulate tumor microenvironment to improve immunotherapy efficacy. This real-world study sought to investigate the efficacy and safety of anlotinib combined with PD-1 inhibitors in the treatment of advanced non-small cell lung cancer (NSCLC). Methods: In total, 42 advanced NSCLC patients were included in this retrospective study. All the patients received anlotinib combined with PD-1 inhibitors from May 2020 to November 2022. The progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) of the patients were evaluated. Results: The patients had an overall median PFS of 5.721 months [95% confidence interval (CI): 1.365-10.076]. The median PFS and ORRs of the male patients compared to the female patients were 10.553 vs. 4.340 months, and 36.4% vs. 0.0%, respectively (P=0.010 and 0.041). The DCRs for the first-, second-, and third-line therapies were 100%, 83.3%, and 64.3%, respectively (P=0.096). In relation to the pathological types, the ORRs of the sarcoma, squamous, and adenocarcinoma patients were 100.0%, 33.3%, and 18.5%, respectively (P=0.025). The DCRs of patients with the tumor protein 53 (TP53) mutation, other status, and epidermal growth factor receptor (EGFR) mutations were 100.0%, 81.5%, and 40.0%, respectively (P=0.020). All-grade AEs occurred in 52.38% of the patients. The grade 3 AEs were hypertension (7.14%), pneumonia (2.38%), and oral mucositis (2.38%). In total, 3 patients discontinued treatment due to anemia, oral mucositis, and pneumonia, respectively. Conclusions: Anlotinib combined with PD-1 inhibitors has potentially good efficacy and a tolerated safety profile in the treatment of advanced NSCLC patients.

Afatinib 30 mg in the treatment of common and uncommon EGFR-mutated advanced lung adenocarcinomas: a retrospective, single-center, longitudinal study.

Background: Afatinib 30 mg has been proved to be with comparable efficacy but more tolerable than the dose of 40 mg for Asian patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical outcomes of afatinib at 30 mg/d in the treatment of advanced lung adenocarcinomas (LAD) with common and uncommon epidermal growth factor receptor (EGFR) mutations. Methods: EGFR-mutated advanced LAD patients receiving afatinib (30 mg/d) from January 2017 to November 2021 were retrospectively included. EGFR status was classified into three subtypes, namely common mutations including exon 19 deletions (19del) and exon 21 L858R (21L858R), uncommon mutations including G719X, L861Q, S768I, and complex mutations, and separately exon 20 insertions (20ins). Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events (AEs) were analyzed during regular follow-up. Results: The overall median PFS of totally 58 included patients was 9.83 [95% confidence index (CI): 5.76-13.91] months. The number of patients with common, uncommon, and 20ins mutations was 32 (55.2%), 19 (32.8%) and 7 (12.1%), respectively. Baseline characteristics did not differ significantly among the three subtypes. The corresponding median PFS was 13.97 (12.06-15.89), 8.48 (0.32-16.64), and 3.78 (1.93-5.64) months, respectively (P=0.002). In the first-line setting, patients with common and uncommon mutations had a significantly longer PFS compared to those with 20ins [14.53 (13.53-15.53) vs. 10.39 (4.87-15.91) vs. 2.37 (0.00-5.11) months, P<0.001]. The first-line ORR showed significant differences among the three subtypes (60% vs. 80% vs. 0.0%, P=0.023). All-grade AEs occurred in 22 patients (37.9%). AEs ≥ grade 3 mainly included diarrhea (8.6%), and none of the patients discontinued treatment due to severe AEs. Conclusions: Afatinib at 30 mg/d is associated with a favorable efficacy and tolerability in the treatment of advanced LAD with common and major uncommon EGFR mutations except 20ins. Further large-scale prospective studies are warranted to confirm our findings.

Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer.

BACKGROUND: Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC. RESULTS: The prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 ± 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously up-regulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration. CONCLUSION: GC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC. Trial registration 2020-KYSB-094. Registered 23 March 2020-Retrospectively registered.

Measurement for overcapacity and its influencing factors on the construction industry-evidence from China's provincial data.

Achieving "Responsible Consumption and Production" is one of the 17 sustainable development goals set by the United Nations. Controlling overcapacity is an important guarantee in order to achieve this goal. There are many types and large quantities of raw materials in the construction industry, which easily leads to overcapacity. Studying the problems related to overcapacity in the construction industry helps to understand the formation mechanism of overcapacity in related industries. This puts forward targeted countermeasures and suggestions for the capacity resolution to achieve green and sustainable development. Based on this, this paper uses the construction industry capacity utilization data of the Shandong Province in China from 2005 to 2017. It also uses the production function method to construct a construction industry overcapacity calculation model to estimate the construction industry capacity utilization and overcapacity rate in Shandong Province. The DEA method was used to construct an extraction model of influencing factors for overcapacity. The results show that the capacity utilization ratio for Shandong Province from 2005 to 2016 was 81.98%. There was no overcapacity as a whole, but there were large fluctuations in capacity utilization for some time periods. Suggestions for optimization countermeasures were also proposed.

High sensitive detection of circulating tumor cell by multimarker lipid magnetic nanoparticles and clinical verifications.

Tumor cells with heterogeneity and diversity can express different markers. At present, positive separation of circulating tumor cells (CTC) taking EpCAM as the marker was used in most cases which could be one-sided, while this study successfully prepared four antibody-modified magnetic immunoliposomes (MIL) by using the self-assembled liposome with antibody derivatives. This study aims to explore the separation efficiency and clinical detection feasibility of single or combined use of MIL with multi-tumor markers on different tumors. Captured CTC were stained with CK-FITC, CD45-PE and DAPI, and fluorescence microscope was used for the observation, analysis and calculation. The result indicated that the CTC number positive rate in blood samples of four different magnetic balls on the same patient could be up to 87.5% in 32 patients with 14 different kinds tumors. While the effect of directly mixed separation by four kinds of magnetic balls was not satisfying. It suggested that the MIL of multi-tumor markers could be a powerful tool for CTC separation in application of tumor screening and prognosis.