Evaluating the Clinical Characteristics and Prognosis of Advanced Non-Small Cell Lung Cancer with Exon 20 Insertions.

BACKGROUND: Epidermal growth factor receptor exon 20 insertion (EGFR ex20ins), an uncommon mutation in non-small cell lung cancer (NSCLC), can induce poor patient response to EGFR tyrosine kinase inhibitors (EGFR-TKI). However, the clinical features and prognosis of patients with EGFR ex20ins are not clearly understood. This study investigated the clinical characteristics and prognosis of advanced NSCLC patients with EGFR ex20ins. METHODS: Advanced NSCLC patients treated at Fujian Cancer Hospital were consecutively recruited from June 1, 2014 to December 20, 2021 and retrospectively examined. EGFR ex20ins was identified by polymerase chain reaction (PCR) or next-generation sequencing (NGS). The clinical characteristics, treatment methods, and patient outcomes were retrieved from the hospital database. The progression-free survival (PFS)  and overall survival (OS) were assessed by Kaplan-Meier analysis. RESULTS: Fourteen mutation subtypes of EGFR ex20ins were identified in the 24 enrolled patients, with EGFR ex20ins mutation more prevalent in non-smoking women. A763_Y764insFQEA and A767_V769dup (12.5% for both) were the most common mutation subtypes. Notably, no significant differences in PFS and OS were found between the first-line targeted therapy group [PFS: 257 days, 95% confidence interval (CI): 116-397 days; OS: not reached] and chemotherapy-based combination therapy group (PFS: 182 days, 95% CI: 156-207 days; OS: 998 days, 95% CI: 674-1321 days). TP53 mutation was the commonest concomitant mutation (62%), followed by EGFR amplification (25%). Chemotherapy combined with immunotherapy improved the prognosis of patients with high PD-L1 expression. CONCLUSION: For NSCLC patients with EGFR ex20ins, limited therapeutic benefits can be gleaned from either EGFR-TKIs or chemotherapy-based combination therapy.

EGFR-TKIs have limited efficacy in NSCLC patients with EGFR ex20ins. Combining chemotherapy with immunotherapy may represent a promising treatment approach for individuals with positive ex20ins and high PD-L1 expression.

PPI Identification of Immune-Related Biomarkers in Esophageal Cancer on the Basis of Gene Co-Expression Network.

Background: The mortality rate of esophageal cancer is on the continuous increase. Fortunately, with the development of immunotherapy, the prognosis and survival rate of patients with esophageal cancer have been improved gradually. Objective: Immune markers have a crucial part in immunotherapy. Therefore, it is of great meaning to delve further into immune-related biomarkers of esophageal cancer for better treatment. Materials and Methods: In this study, gene co-expression networks were established using weighted gene co-expression network analysis, thus forming gene modules with different clusters. The tumor immune microenvironment was assessed with the ESTIMATE algorithm. Results: Analysis of the module Eigen gene -immune score trait indicated that the black module was markedly associated with immune score, with the top 80 genes regarding correlation ranking as the candidate hub gene set. Enrichment analysis revealed that genes within the black module were primarily enriched in tumor immune-related functions. To mine the hub genes that were closely connected with immunity, protein-protein interaction networks were constructed by STRING for genes within the black module, and genes with the interaction score top10 were retained. They were intersected with hub genes to finally obtain four hub genes: CCR5, LCP2, PTPRC and TYROBP. The samples were divided into high- and low-expression groups by the median expression of hub gene, and survival analysis was performed in combination with clinical information. The results revealed that the high-expression groups of genes LCP2 and PTPRC had a poor prognosis. TIMER immune cell infiltration analysis revealed that the expression levels of the 4 hub genes were positively correlated with immune cell infiltration and negatively correlated with tumor purity. In addition, these 4 hub genes were correlated with the expression of immune checkpoint genes CTLA-4 and PDCD1 positively. Gene set enrichment analysis enrichment analysis demonstrated that there were differences in tumor immunity and cancer-related pathways between high and low expression of 4 hub genes. Conclusion: Altogether, we identified four biomarkers that may have connection with tumor immunity, and speculated that these genes may influence patient prognosis by affecting pathways related to esophageal cancer immunity. This study will pave the way for the research of immune mechanisms of esophageal cancer and the analysis of patient's prognosis.

Random forest model can predict the prognosis of hospital-acquired Klebsiella pneumoniae infection as well as traditional logistic regression model.

OBJECTIVE: To explore if random forest (RF) model can predict the prognosis of hospital-acquired Klebsiella pneumoniae infection as well as traditional logistic regression(LR) model. METHODS: A total of 254 cases of hospital-acquired Klebsiella pneumoniae infection in a tertiary hospital in Beijing from January 2016 to December 2020 were retrospectively collected. Appropriate influencing factors were selected by referring to relevant articles from the aspects of basic clinical information and contact history before infection, and divided into a training set and a test set. Both the RF and LR models were trained by the training set, and using testing set to compare these two models. RESULTS: The prediction accuracy of the LR model was 87.0%, the true positive rate of the LR model was 94.7%; the false negative rate of the LR model was 5.3%; the false positive rate of the LR model was 35%; the true negative rate of the LR model was 65%; the sensitivity of the LR model for the prognosis prediction of hospital-acquired Klebsiella pneumoniae infection was 94.7%; and the specificity was 65%. The prediction accuracy of the RF model was 89.6%; the true positive rate of the RF model was 92.1%; the false negative rate of the RF model was 7.9%; the false positive rate of the RF model was 21.4%; the true negative rate of the RF model was 78.6%; the sensitivity of the RF model for the prognosis prediction of hospital-acquired Klebsiella pneumoniae infection was 92.1%; and the specificity was 78.6%. ROC curve shows that the area under curve(AUC) of the LR model was 0.91, and that of the RF model was 0.95. CONCLUSION: The RF model has higher specificity, sensitivity, and accuracy for the prognostic prediction of hospital-acquired Klebsiella pneumoniae infection than the LR model and has greater clinical application prospects.

Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: a retrospective, single-center, three-arm study.

Background: Pembrolizumab has been shown to have a powerful benefit for locally advanced or metastatic esophageal cancer. The aim of present study was to evaluate the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for locally advanced and potentially resectable esophageal squamous cell carcinoma (ESCC). Methods: Patients diagnosed with clinical stage III-IV ESCC and have a chance of resectability at Fujian Provincial Hospital were included into this study. Patients received pembrolizumab in combination with paclitaxel and nedaplatin as induction therapy once every 3 weeks in the first stage. After 4 cycles of pembrolizumab therapy, the patients then chose to undergo radical surgery (group A), radical radiotherapy (group B), or neither (group C). In the third stage, maintenance treatment with pembrolizumab was administered to all patients. Results: A total of 39 patients (33 male and 6 female) with a median age of 64 years were included. After immune response evaluation in the first stage, 34 (87.2%) patients achieved immune partial response (iPR), and 5 (12.8%) patients achieved immune stable disease (iSD). The objective response rate (ORR) was 87.2% (34/39), and the disease control rate (DCR) was 100%. In the second stage, 22 patients received radical surgery, all of whom achieved R0 resection. The major pathological response (MPR) rate was 68.2% (15/22), and the pathological complete response (pCR) rate was 45.5% (10/22). Of the patients, 9 chose radiotherapy as the radical therapeutic method and 8 chose not to undergo any radical therapy. The median period of pembrolizumab therapy was 8 cycles (4-22 cycles). The median follow-up time was 14 months (3-34 months). The median overall survival and progression-free survival (PFS) times were not reached. The incidence of severe adverse events (AEs) (grade ≥3) was 15.4% (6/39). Conclusions: Pembrolizumab combined with paclitaxel and platinum for locally advanced and potentially resectable ESCC has a high ORR, high surgical conversion, MPR, pCR, and R0 resection rates, and tolerable AEs. Also, pembrolizumab could provide good benefits in sequential treatment with radical radiotherapy or maintenance therapy.

miR-9-5p Promotes Lung Adenocarcinoma Cell Proliferation, Migration and Invasion by Targeting ID4.

Objectives Evidence reveals that microRNAs (miRNAs) are abnormally expressed in lung adenocarcinoma (LUAD) tissue and are crucial in LUAD occurrence. Therefore, this study aims to find the miRNA which could regulate LUAD and to further explore its regulatory mechanism, thus providing a potential molecular target for LUAD. Methods miR-9-5p and ID4 expression in LUAD cells were measured by real-time quantitative PCR and western blot. Cell functional assays were conducted to detect the biological functions of LUAD cells. A dual-luciferase reporter assay was utilized to validate the binding relationship between miR-9-5p and ID4. Results miR-9-5p was highly expressed whereas ID4 was lowly expressed in LUAD. miR-9-5p facilitated LUAD cell progression by targeting ID4. Conclusion miR-9-5p promotes LUAD cell progression by modulating ID4 and may become a potential target for LUAD.

LINC00346 Sponges miR-30c-2-3p to Promote the Development of Lung Adenocarcinoma by Targeting MYBL2 and Regulating CELL CYCLE Signaling Pathway.

BACKGROUND: LINC00346 has recently been reported to regulate the development of several cancer types, but its biological functions and underlying mechanisms in lung adenocarcinoma (LUAD) have not been elucidated. The purpose of this study was to investigate the molecular mechanism of LINC00346 in the progression of LUAD. METHODS: Bioinformatics was performed to find the target lncRNA, miRNA and mRNA, and the binding relationship between the target genes was verified by dual luciferase reporter gene and RIP assays. Fluorescence in situ hybridization was used to detect the location of LINC00346 in LUAD tissues. The expressions of LINC00346, miR-30c-2-3p and MYBL2 in each group were detected by qRT-PCR, and western blot was performed to detect expressions of MYBL2 and CELL CYCLE related proteins. Proliferation, metastasis, apoptosis and cell cycle of LUAD cells were detected by CCK-8, colony formation, Transwell and flow cytometry assays, respectively. Mouse xenograft models were established to further determine the effects of LINC00346 on LUAD tumor growth in vivo. RESULTS: LINC00346 was upregulated in LUAD tissues and cells and was mainly localized in the cytoplasm. Knockdown of LINC00346 inhibited tumor growth in vivo, proliferation, metastasis and cell cycle progression, while induced apoptosis. LINC00346 sponged miR-30c-2-3 by targeting MYBL2 and regulating CELL CYCLE signaling pathway. Inhibiting miR-30c-2-3p or overexpressing MYBL2 could reverse the inhibitory effect of LINC00346 knockdown on LUAD process. CONCLUSIONS: LINC00346 as a ceRNA played a carcinogenic role in the development of LUAD via miR-30c-2-3p/MYBL2 axis regulating the CELL CYCLE signaling pathway. The study generally elucidated the mechanism by which LINC00346 regulated the development of LUAD, providing new ideas for the diagnosis and treatment of LUAD guided by lncRNA.

Affordable measures to monitor and alarm nosocomial SARS-CoV-2 infection due to poor ventilation.

Since the coronavirus disease 2019 (COVID-19) outbreak, the nosocomial infection rate worldwide has been reported high. It is urgent to figure out an affordable way to monitor and alarm nosocomial infection. Carbon dioxide (CO2 ) concentration can reflect the ventilation performance and crowdedness, so CO2 sensors were placed in Beijing Tsinghua Changgung Hospital's fever clinic and emergency department where the nosocomial infection risk was high. Patients' medical records were extracted to figure out their timelines and whereabouts. Based on these, site-specific CO2 concentration thresholds were calculated by the dilution equation and sites' risk ratios were determined to evaluate ventilation performance. CO2 concentration successfully revealed that the expiratory tracer was poorly diluted in the mechanically ventilated inner spaces, compared to naturally ventilated outer spaces, among all of the monitoring sites that COVID-19 patients visited. Sufficient ventilation, personal protection, and disinfection measures led to no nosocomial infection in this hospital. The actual outdoor airflow rate per person (Qc ) during the COVID-19 patients' presence was estimated for reference using equilibrium analysis. During the stay of single COVID-19 patient wearing a mask, the minimum Qc value was 15-18 L/(s·person). When the patient was given throat swab sampling, the minimum Qc value was 21 L/(s·person). The Qc value reached 36-42 L/(s·person) thanks to window-inducted natural ventilation, when two COVID-19 patients wearing masks shared the same space with other patients or healthcare workers. The CO2 concentration monitoring system proved to be effective in assessing nosocomial infection risk by reflecting real-time dilution of patients' exhalation.

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) provided a paradigm shift for advanced non-small cell lung cancer (NSCLC) treatment and improved the clinical prognosis of such patients. Pembrolizumab is a humanized anti-programmed death cell protein 1 (PD-1) monoclonal antibody, approved for the treatment of patients with advanced or metastatic NSCLC. This article investigated and reported on the efficacy and safety of pembrolizumab in the treatment of advanced NSCLC in our center since 2019. METHODS: Patients with clinical stage III-IV NSCLC treated with pembrolizumab for ≥4 cycles were enrolled as participants in this study. Pembrolizumab was administered intravenously at a dose of 2 mg/kg every 3 weeks. A cycle was defined as 3 weeks of treatment. We assessed the efficacy and safety of pembrolizumab through the collection of researcher-assessed tumor response, survival, and safety data. RESULTS: A total of 24 patients were included in this study. The median follow-up time was 9 months (3-20 months) and the median period of pembrolizumab therapy was 7 cycles (4-21 cycles). The objective response rate (ORR) was 45.8% and disease control rate (DCR) was 70.8%. The median overall survival (OS) and progression-free survival (PFS) times were not reached. A total of 2 programmed death-ligand 1 (PD-L1)-negative participants were treated with pembrolizumab combined with chemotherapy and there was no significant progression during the follow-up period. During the follow-up period, 8 patients underwent surgery. The major pathological response (MPR) was 75% and pathological complete response (pCR) was 50%. A case that was preoperatively diagnosed with clinical stage IV achieved pCR after 6 cycles of pembrolizumab combined with chemotherapy. The incidence of adverse effects (AEs) was 83.3%, and 16.7% of these were serious AEs (grade ≥3), which was similar to the incidence reported in previous studies. CONCLUSIONS: This real-world data supports the use of pembrolizumab for advanced NSCLC, including those cases that are PD-L1 negative. More importantly, pembrolizumab immunotherapy can also provide the potential of local treatment for patients with advanced NSCLC, which has wide application prospects in the field of surgery.

[Project to ameliorate cognitive function deterioration in day care dementia patients].

BACKGROUND & PROBLEMS: Deterioration of cognitive functions, including disorientation related to people, time and place, loss of memory, and deterioration in interpersonal skills, is very common in dementia patients. Expense of care rises as conditions worsen. PURPOSE: The authors designed this project to ameliorate the deterioration of cognitive functions and enhance cognition in daily life. SOLUTION: The project was carried out between Jan 1, 2007 and June 30, 2007. The three strategies used included: (1) educating staff and establishing care guidelines; (2) introducing environmental keys such as a reality-oriented board, clock information, photo labels, and image signs; (3) redesigning and implementing daily activities. RESULTS: Following the intervention, average cognitive functions improved from 6.58 ± 3.19 to 5.11 ± 3.20 (total: 10). The mistaken recognition rate for items including the toilet, personal bed, clothes closet, meal seating position and time decreased from 38% to 13%. CONCLUSION: This project significantly improved cognitive function and recognition in dementia patients. The experience described within may serve as a reference for dementia institutions and healthcare workers.