Analysis of tumor abnormal protein expression and epidermal growth factor receptor mutation status in non-small cell lung cancer.

BACKGROUND: The level of tumor abnormal protein (TAP) level has a significant impact on tumor growth, recurrence, and metastasis. Previous studies have highlighted the influence of the mutations in exons 19 and 21 of the epidermal growth factor receptor (EGFR), particularly the sensitivity displayed by tumor cells to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Our study is centered on exploring the clinical relevance of TAP and EGFR mutations in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: In this study, tissue samples were collected from a total of 176 patients diagnosed with non-small cell lung cancer (NSCLC). Real-time PCR technology was utilized to detect mutations within exons 19 and 21 of the epidermal growth factor receptor (EGFR) gene in these samples. This approach enables precise identification of EGFR mutations associated with NSCLC. Furthermore, the study investigated the impact of various tumor markers, including tumor abnormal protein (TAP) and carcinoembryonic antigen (CEA), on EGFR mutation status. Established assays were employed to evaluate TAP and CEA levels, aiming to ascertain their potential correlation with EGFR mutation in NSCLC patients. RESULTS: EGFR exhibited mutation rates of 23.86% and 12.50% in exons 19 and 21, respectively. EGFR mutations were more prevalent in younger women (< 60 years old) and in cases with pleural invasion, vessel invasion, CEA > 6.5 ng/mL, and TAP > 228 µm2 for both genders. Increased TAP levels independently predicted EGFR mutations (P = 0.001 for males; P = 0.000 for females). An area under the curve (AUC) of 0.833 indecated EGFR mutation prediction with sensitivity and specificity of 79.7% and 87.0%, respectively. For females, the sensitivity increased to 89.7% and specificity increased to 93.8%. CONCLUSIONS: TAP effectively predicts EGFR mutations in NSCLC patients with moderate accuracy, particularly benefiting diagnosis in females with high sensitivity and specificity. Integrating TAP assessment into EGFR mutation testing can significantly enhance diagnostic precision, especially in female NSCLC cases.

XAF1 overexpression inhibits the malignant progression and cisplatin resistance of NSCLC by activating endoplasmic reticulum stress.

BACKGROUND: XIAP-associated factor 1 (XAF1) has been found to participate in the progression of multiple human cancers. Nevertheless, its role as well as the reaction mechanism in non-small cell lung cancer (NSCLC) still remains obscure. METHODS: In this study, the protein expression of XAF1 in NSCLC cell lines was evaluated using western blot. With the employment of CCK-8 assay, EdU staining, wound healing and transwell, capabilities of NSCLC cells to proliferate, migrate and invade were assessed. Cell apoptotic level and cell cycle were resolved utilizing flow cytometry. Western blot was applied for the estimation of apoptosis- and endoplasmic reticulum (ER) stress-related proteins. RESULTS: It was discovered that XAF1 expression was conspicuously reduced in NSCLC cell lines. XAF1 overexpression suppressed H1299 cell proliferative, invasive and migrative capabilities, but exhibited promotive effects on cell cycle arrest. Meanwhile, XAF1 overexpression inhibited cisplatin resistance in H1299 and H1299/DDP cells by promoting cell apoptosis and enhanced the expression levels of ER stress-related proteins CHOP, GRP78 and ATF4. What's more, 4-PBA treatment reversed the impacts of XAF1 overexpression on the proliferative, invasive, migrative and apoptotic capabilities of H1299 cells, as well as cell cycle and cisplatin resistance. CONCLUSION: In conclusion, XAF1 overexpression impeded the advancement of NSCLC and repressed cisplatin resistance of NSCLC cells through inducing ER stress, which indicated that XAF1 might be a novel targeted-therapy for NSCLC.

Identification of epithelial-mesenchymal transition-related biomarkers in lung adenocarcinoma using bioinformatics and lab experiments.

BACKGROUND: Lung adenocarcinoma accounts for approximately 40% of lung cancer cases and poses a serious threat to human health. Therefore, there is an urgent need to identify central biomarkers in lung adenocarcinoma. METHODS: We first identified the EMT-associated genes in LUAD based on the TCGA cohort. Then we screened these 90 EMT-associated genes using univariate Cox regression analysis and LASSO regression analysis to develop a prognostic gene signature in the training set. The predictive performance of the gene signature was assessed in the validation set and multiple external test sets using the ROC cure, C index and log-rank tests. RT-PCR, western blot, wound healing assays, and siRNA methods were further used to investigate the role of PLEK2 in tumor behaviors. RESULTS: Eight genes (CCNB1, PLEK2, DERL3, C1QTNF6, DLGAP5, HMMR, GJB3, and SPOCK1) were eventually selected to develop an eight-gene signature. The 5-year AUC of the gene signature has a robust predictive ability both for predicting overall survival (0.774, 0.756, and 0.669 in the external test sets, respectively), and for progression free survival (0.774, 0.746, and 0.755 in the external test sets, respectively). C-index of the gene signature was 0.961 ± 0.005, 0.916 ± 0.011, and 0.868 ± 0.234 in the external test sets, respectively. Four genes (C1QTNF6, DLGAP5, HMMR, and PLEK2) were identified as key genes in LUAD progression, which were upregulated in the cancerous tissue compared with in the normal tissue (P < 0.001), and correlated with an unwanted prognosis in lung cancer (P < 0.05). PLEK2 was used as an example to explore its effect on LUAD progression in vitro using RT-PCR, western blot, CCK8, si-RNA and wound healing assay. Silencing of PLEK2 was shown to reduce proliferative and migrated ability of lung cancer cells via prohibition of autophagy. CONCLUSIONS: This study developed a novel EMT-related gene signature benefiting precision medicine, and identified four pivotal genes which can serve as therapeutic targets in LUAD. Four key genes can serve as molecular targets for patients with LUAD; silencing of PLEK2 was shown to reduce proliferative and migrated ability of lung cancer cells via prohibition of autophagy.

A circadian rhythm-related biomarker for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains a major reason of cancer-associated mortality globally, and there exists a lack of indicators for survival in LUAD patients. Therefore, it is clinically required to obtain a novel prognostically indicator for guiding clinical management. In this study, we established a circadian rhythm (CR) related signature by a combinative investigation of multiple datasets. The newly-established signature showed an acceptable ability to predict survival and could serve as an independent indicator for prognosis. Moreover, the newly-established signature was critically associated with tumor malignancy, including proliferation, invasion, EMT and metastasis. The newly-established signature was predictive of response to immune checkpoint blockade. Collectively, we established a CR-related gene signature that could forecast survival, tumor malignancy and therapeutic response; our findings could help guiding clinical management.

High Expression of Tumor Abnormal Protein Preoperatively Predicts Poor Prognosis of Patients With Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) acts as a fatal malignant tumor among human beings and is marked by late-stage diagnosis, frequent recurrence, metastasis, and therapy resistance. Tumor abnormal protein (TAP) remarkably affects cancer development and progression of human cancers. TAP has been shown to be a biomarker for gastric and lung cancer progression. Nevertheless, the clinical value exhibited by TAP for ESCC has not been well-explained in the current literature. Methods: The present study included 183 ESCC cases who received surgical resection and 183 cases who had normal physical checkup from March 2013 to January 2015 at the People's Hospital of Chizhou, and used the TAP detection agent for evaluating the TAP relative level. Results: As found, ESCC patients presented an obviously higher TAP expression relative to cases who had normal physical checkup. Moreover, TAP expression was significantly downregulated after surgery. Furthermore, the TAP expression was correlated with gender, smoking, pathologic differentiation, and pN stage, but not with age, tumor location, surgical type, pT stage, and vascular invasion. High expression of TAP was significantly correlated with poorer overall survival (OS) rate in ESCC patients. TAP was an independent prognostic predictor in ESCC patients, based on the multivariate survival analysis. Conclusion: The study reveals how TAP upregulation promotes ESCC malignant progression, and concludes that TAP acts as the therapeutic target and potential biomarker specific to ESCC.

Applying Queuing Theory and Mixed Integer Programming to Blood Center Nursing Schedules of a Large Hospital in China.

Blood centers in large hospitals in China are facing serious problems, including complex patient queues and inflexible nursing schedules. This study is aimed at developing a flexible scheduling method for blood center nurses. By systematically analyzing the constraints that affect scheduling, a flexible scheduling model is established based on queuing theory and mixed integer programming. This combined model can reasonably determine the number of nurses required during a given working period and flexibly arrange nursing schedules while ensuring sufficient rest periods for individual nurses. Results of numerical studies conducted using data from a large hospital in China show a significant improvement in patient waiting time performance metrics over the hospital's current practice. In addition, the nurses' workloads and rest periods are well balanced, indicating that the proposed method can effectively and flexibly arrange nursing shifts in blood centers.

Is the result of modified Allen's test still accurate after endoscopic thoracic sympathectomy?

BACKGROUND: The radial artery (RA) is increasingly being used for coronary artery bypass grafting (CABG). Endoscopic thoracic sympathectomy (ETS) has been shown to block innervation of sympathetic nerves of upper limbs, which reduces sweating of hands and dilates blood vessels. The modified Allen's test (MAT) is one of the commonest methods of assessing collateral arm flow prior to RA harvest, though it has limitations. However, the reliability of MAT after ETS remains unclear. We therefore investigated the effects of ETS on the results of MAT. METHODS: A retrospective cohort study was conducted on 164 consecutive Chinese patients with palmar hyperhidrosis who underwent ETS between January 2016 and January 2019. The medical records were reviewed concerning the ultrasound examination and MAT results of their RAs and ulnar arteries (UAs) in both forearms before and after ETS. RESULTS: The performance of ETS significantly increased the diameter of the right RA from 2.731±0.122 to 3.102±0.114 mm in men and from 2.347±0.074 to 2.915±0.162 mm in women. Similar effects of ETS were observed in expanding the diameters of the left RA and the UA. Meanwhile, there was no significant effect of ETS on systolic blood pressure (BP) and heart rate (HR). Overall, retesting of patients following ETS with a preoperative positive MAT result revealed a transition to a negative result. CONCLUSIONS: ETS was effective in dilating RA in both men and women, which could lead to a false negative preoperative MAT result. Patients should be questioned about their history of ETS if their RAs are to be harvested for CABG. More studies are warranted to evaluate the safety of RA as a coronary artery graft after ETS.

Increased Expression of TAP Is Predictive of Poor Prognosis in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: The most common cancer among humans is lung cancer. Non-small cell lung cancer (NSCLC) comprises the majority of these cases. In the development and progression of cancers across the spectrum, tumor abnormal protein (TAP) plays crucial roles. Additionally, in the advancement of the bladder and colorectal cancers, the involvement of glycoproteins like TAP is present. However, it is worth noting that current literature has yet to clarify the clinical significance of the TAP in NSCLC. METHODS: In the present study, to evaluate the relative level of TAP, we utilized a TAP detection agent in 154 cases of NSCLC and normal patients who underwent surgical resection anytime from March 2013 to January 2019 at the People's Hospital of Chizhou. RESULTS: Our results demonstrated that in NSCLC patients, the expression level of TAP was significantly higher than in normal patients. Moreover, after surgery, TAP expression was significantly downregulated in NSCLC patients. TAP expression is associated with an array of factors, which include the patient's sex, history of smoking use, tumor size, pTNM, distant cancer, metastasis of lymph nodes, invasive and aggressive indicator pleural invasion, and differentiation degree of NSCLC. Additionally, TAP has no association with the patient's age, history of drinking, location of the tumor, hypertension, and diabetes. In NSCLC patients, a poor overall survival rate within 5 years is significantly correlated with the increased TAP expression. For NSCLC patients, an independent prognostic factor is the TAP, which is confirmed using the multivariate survival analysis. CONCLUSION: In the malignant progression of NSCLC, our results demonstrate how the promoting role of the upregulated TAP expression takes place. Hence, a therapeutic aim for NSCLC and a potential biomarker for NSCLC progress is a TAP.

[Effect of High-frequency Chest Wall Oscillatory on Lung Function in Patient 
After Single Port Video-assisted Thoracoscopic Surgery Lobectomy].

BACKGROUND: It has been confirmed that high-frequency chest wall oscillatory (HFCWO) is a new type of auxiliary sputum discharge device. However, up to now, the specific therapeutic effect of HFCWO is still uncertain. This study aimed to compare the changes of the sputum volume before and after the treatment of HFCWO, and to investigate the effect of HFCWO on lung function and arterial blood gas analysis after single port video-assisted thoracoscopic surgery lobectomy (S-VATS). METHODS: A total of 90 patients with S-VATS lobectomy were collected in the Second Affiliated Hospital of Soochow University from January 2017 to December 2017, which were randomly divided into the experimental group with HFCWO (n=45) and the control group (n=45) with routine clapping, respectively. The sputum volume of the two groups was measured 5 days before operation. Lung function and arterial blood gas analysis was measured before and 7th days after surgery. RESULTS: The sputum volume was higher in the experimental group than that of the control group after surgery, there was statistically significant difference for the first three days (P<0.05). There was no statistically significant difference between the two groups in forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and oxygen partial pressure (PaO2) before surgery (P>0.05); Compared with those before surgery, FEV1, FVC and PaO2 decreased in both groups after surgery (P<0.05); However, FEV1, FVC and PaO2 in the experimental group were higher than those in the control group (P<0.05); There was no statistically significant difference in preoperative and postoperative partial pressure of carbon dioxide (PaCO2) between the two groups (P>0.05). CONCLUSIONS: HFCWO can significantly increase the amount of sputum excretion, improve lung function and alleviate hypoxia status after S-VATS lobectomy. This study provides a promising approach for HFCWO toward hypoxia status after S-VATS lobectomy.
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Surgical treatment of an esophageal bronchogenic cyst with massive upper digestive tract hematoma without esophagectomy: a case report and the review of the literature.

Esophageal bronchogenic cysts are extremely rare. Here we report a case of massive upper digestive tract hematoma and bronchogenic cyst mimicking aortic dissection that was safely removed without esophagectomy. A 30-year-old man was referred to our hospital for the treatment of a mediastinal cystic tumor located in the submucosa of the distal esophagus. His chief complaints were dysphagia > 1 week and severe persistent upper abdominal pain mimicking aortic dissection with constant vomiting for 1 day after gastroscopy examination. The serum level of carbohydrate antigen (CA)199 was > 1,000 U/mL and CA125 was 4,816 U/mL. Hemoglobin levels decreased from 122 g/L to 85 g/L in 5 days. Imaging examinations detected a huge hematoma of the gastric wall. Preoperative diagnosis was difficult. Although the pain indicated a possible aortic dissection, the abnormal levels of tumor biomarkers suggested malignancy. The patient underwent left thoracotomy. The cyst showed an exophytic lesion connected to the esophageal wall at the level of the gastroesophageal junction. Muddy brown contents were obtained by aspiration of the mass intraoperatively. Because enucleation could not be performed, esophageal myotomy in the distal esophagus and partial resection of the cyst were selected. Histopathological examination indicated a bronchogenic cyst of the esophagus. At a follow-up visit 3 months later, the patient had no signs of disease recurrence or any complaints. Postoperative tumor biomarkers returned to normal range. The present report summarizes the clinical details of the case and reviews the literature in order to improve the accuracy of diagnosis.

A MIP Model for Rolling Horizon Surgery Scheduling.

Most surgery scheduling is done 1 day in advance. Caused by lack of overall planning, this scheduling scheme often results in unbalanced occupancy time of the operating rooms. So we put forward a rolling horizon mixed integer programming model for the scheduling. Rolling horizon scheduling refers to a scheduling scheme in which cyclic surgical requests are taken into account. Surgical requests are updated daily. The completed surgeries are eliminated, and new surgeries are added to the scheduling list. Considering day-to-day demand for surgery, we develop a non-rolling scheduling model (NRSM) and a rolling horizon scheduling model (RSM). By comparing the two, we find that the quality of surgery scheduling is significantly influenced by the variation in demand from day to day. A rolling horizon scheduling will enable a more flexible planning of the pool of surgeries that have not been scheduled into this main blocks, and hence minimize the idle time of operating rooms. The strategy of the RSM helps balance the occupancy time among operating rooms. Using surgical data from five departments of the West China Hospital (WCH), we generate surgical demands randomly to compare the NRSM and the RSM. The results show the operating rooms' average utilization rate using RSM is significantly higher than when applying NRSM.

Sequence-dependent anesthesia-controlled times: a retrospective study in an ophthalmology department of a single-site hospital.

BACKGROUND: Anesthesia-controlled time (ACT) generally refers to the time durations before and after the period of surgery. The ACT is typically dependent on the sequence of 2 consecutive surgeries and thus adds to the complexity of operating room scheduling. We report a study on sequence-dependent ACTs at the West China Hospital (WCH), focusing on elective surgeries (also referred to as "procedures" below) performed by the ophthalmology department of WCH over a 5-year period, 2007 to 2012. METHODS: ACTs associated with 4 high-volume procedures: phacoemulsification, vitrectomy, strabismus correction, and glaucoma filtration. A total of 29,452 cases were studied, classified into 4 groups according to the sequence of the procedures involved. Specifically, P-P plots were used to determine the distributions of the ACTs, Kruskal-Wallis H test, Nemenyi test, and Student t test were performed to examine the sequence-dependent nature of the ACTs, and the t test was also applied to examine the advantage of sequencing the same procedures consecutively. Permutations were enumerated to identify the best sequence when different procedures were involved. Monte Carlo simulation was used to compute the total completion time, ACTs plus surgical periods, of any given sequence of procedures. RESULTS: We confirm via statistical tests that the ACTs follow lognormal distributions, and identify their corresponding means and variances. Furthermore, we verify that the ACTs are statistically different in means: they are sequence dependent in general. Using statistical tests, we conclude that it is best to sequence identical procedures consecutively, and we also identify the best sequence involving different procedures. Using Monte Carlo simulation, we compared the daily completion times using the best sequences we have identified against actual data from WCH over a 2-year period; the average reduction is 4.7% (with a standard error (SE) of ± ± 0.5%). CONCLUSIONS: ACTs are usually sequence dependent and hence should be considered in operating room scheduling. Although identifying the best sequence in general is a difficult optimization problem, in certain departments (such as the ophthalmology department of WCH) where a set of high-volume small-variety procedures is present, the best sequences can be systematically identified using a combination of statistical tests and Monte Carlo simulation as illustrated in this study.