Publications by authors named "Zhenxiang Li"

50 Publications

Current status and influencing factors of nursing interruption events.

Am J Manag Care 2021 Jun 1;27(6):e188-e194. Epub 2021 Jun 1.

Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Rd, Ji'nan, Shandong, China 250021. Email:

Objectives: To investigate the status of nursing interruption events during medicine administration and to analyze the factors influencing interruptions.

Study Design: The nursing drug delivery process was divided into 3 segments: the processing of doctors' orders, drug allocation, and bedside drug administration. The frequency, source, type, and outcome of interruption events during these 3 segments were observed. The interruption time and medication errors caused by interruptions were analyzed.

Methods: The structural observation method was used to observe the 3 steps of the drug delivery process. The observations were performed between 8:30 and 10:30 and between 13:30 and 14:30. Count data are described as frequency, composition ratio, and cumulative percentage. R×C contingency table, t tests, and analysis of variance were used to analyze the data.

Results: In 270 hours of observation, 3424 nursing interruptions occurred, for a mean of 12.68 interruptions per hour. The mean (SD) interruption time was 28.03 (11.01) seconds, and the total duration of drug administration interruptions was 26.65 hours, accounting for 9.87% of the total observation time. The sources of interruption events were as follows: family members, the environment, doctors, patients, colleagues, the nurses themselves, and others; of these interruptions, 2340 were low-priority events (eg, visitor inquiry, telephone call, consultation, discharge questions), accounting for 68.34%. The incidence of medication errors due to interruptions was 1.139%.

Conclusions: Nursing interruption events occur frequently, come from many sources, have complex causes, and commonly lead to negative outcomes. Interruption also has a time cost and can directly lead to medication errors.
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http://dx.doi.org/10.37765/ajmc.2021.88667DOI Listing
June 2021

Implementing a Pressure Injury Care Bundle in Chinese Intensive Care Units.

Risk Manag Healthc Policy 2021 4;14:2435-2442. Epub 2021 Jun 4.

Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China.

Background: The incidence of pressure injury (PI) in intensive care units (ICUs) is high with a low compliance rate for PI prevention standard care. Although studies have confirmed that PIs are largely preventable, a PI care bundle based on the best evidence in Chinese ICUs is lacking.

Aim: The aims of this study are to assess the effectiveness of our PI care bundle-which is based on the best evidence and designed to prevent the development of ICU PIs-and to identify the changes in nurse compliance rates during the implementation process.

Methods: A quasi-experimental, pre- and post-intervention design was used. Implementation strategies included training, auditing during the use of the care bundle, and measuring outcome indicators in the ICU. The key elements of the care bundle were risk identification, skin assessment, patient repositioning, skin care, use of a pressure-reducing device, and nutrition. The number and stage of PIs were collected at three time points by unit staff. The implementation compliance rate was measured at two time points using a compliance checklist.

Results: Pressure injury rates were reduced significantly from 13.86% to 10.41%. The incidence of new hospital-acquired pressure injuries (HAPI) decreased by 29.5% within 6 months. The compliance rate of nurses increased significantly from 55.15% to 60.15% before and after the implementation of the care bundle (χ=16.72, P=0.00); This result may be attributable to the implementation of care bundle training for nurses and the audit.

Conclusion: A standardized care bundle based on the best evidence is indicated to effectively reduce the incidence of PIs. The increase in compliance rate after the intervention may benefit from nurses training in the care bundle and the audit during the intervention.
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http://dx.doi.org/10.2147/RMHP.S292579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187104PMC
June 2021

Silencing LINC01116 suppresses the development of lung adenocarcinoma via the AKT signaling pathway.

Thorac Cancer 2021 Jul 1;12(14):2093-2103. Epub 2021 Jun 1.

Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Background: A growing body of evidence has proven that long noncoding ribonucleic acids (lncRNAs) are important epigenetic regulators that play crucial parts in the pathogenesis of human cancers. Previous studies have shown that long intergenic nonprotein coding RNA 01116 (LINC01116) is a carcinogen in several carcinomas; however, its function in lung adenocarcinoma (LUAD) has not been clarified. Here, we aimed to investigate the role of LINC01116 in LUAD.

Methods: The relative expression levels of LINC01116 in LUAD cell lines and tissues were detected by quantitative reverse transcription polymerase chain reaction. A Kaplan-Meier survival analysis was performed using patient information from the Gene Expression Profiling Interactive Analysis (GEPIA) database. LUAD proliferation, invasion, migration, and apoptosis were measured by performing cell counting kit-8, colony formation, transwell, wound healing, and flow cytometric assays. A xenograft animal experiment was performed to investigate the effect of LINC01116 in vivo. Protein kinase B (AKT) signaling pathway-related protein expressions were tested by Western blot assay.

Results: LINC01116 expression was upregulated in LUAD cells and tissues. The loss-of-function experiments on LUAD cells revealed that silencing LINC01116 expression could decrease cell viability both in vitro and in vivo. Furthermore, silencing LINC01116 inhibited LUAD cell invasion and migration and induced cell apoptosis. Mechanically, silencing LINC01116 significantly decreased p-AKT protein levels, and an AKT pathway stimulator could rescue the suppressive effects of small interfering LINC011116-specific RNAs on LUAD development.

Conclusions: Our study demonstrated that silencing LINC01116 suppresses the development of LUAD via the AKT signaling pathway.
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http://dx.doi.org/10.1111/1759-7714.14042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287011PMC
July 2021

Impact of Radiotherapy Pattern on the Prognosis of Stage IV Lung Adenocarcinomas Harboring EGFR Mutations.

Cancer Manag Res 2021 15;13:3293-3301. Epub 2021 Apr 15.

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People's Republic of China.

Introduction: The aim of this study was to investigate the role of local radiotherapy in the management of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancers (NSCLCs) treated with EGFR tyrosine kinase inhibitors (TKIs).

Materials And Methods: Patients with stage IV EGFR-mutant NSCLC treated with radiotherapy concomitant to EGFR TKIs from May 2010 to December 2017 were retrospectively identified. Overall survival (OS) was the primary endpoints of the study.

Results: A total of 205 patients were enrolled in the study. One hundred eleven patients received one-time single-site radiotherapy (SSR), and 94 patients received multiple-site radiotherapy (MSR). Patients who received MSR had longer OS (median OS, 40.0 months; 95% confidence interval [CI], 29.6 to 50.4) than those who received SSR (median OS, 28.9 months; 95% CI, 24.3 to 33.5; =0.031). Thoracic radiotherapy was associated with prolonged median OS (41.7 months, 95% CI, 29.0 to 54.4 vs 27.1 months, 95% CI 22.7 to 31.5; log-rank <0.001). Multivariate analysis confirmed that thoracic radiotherapy was independently associated with improved OS (adjusted hazard ratio [HR], 0.514; 95% CI 32.3% to 81.8%; =0.005).

Conclusion: MSR improves survival outcomes in patients with advanced-stage, EGFR-mutant, lung adenocarcinoma, with thoracic radiotherapy having the most significant effect on prognosis.
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http://dx.doi.org/10.2147/CMAR.S299563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055281PMC
April 2021

Survival analysis for non-squamous NSCLC patients harbored STK11 or KEAP1 mutation receiving atezolizumab.

Lung Cancer 2021 04 17;154:105-112. Epub 2021 Feb 17.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China. Electronic address:

Objective: To analyze the prognostic effect for patients with non-squamous non-small cell lung cancer (NSCLC) harbored STK11 or KEAP1 (STK11/KEAP1) mutations receiving atezolizumab and docetaxel.

Methods: Data from OAK and POPLAR clinical trials was firstly applied to analyze genomic alteration frequency and the correlation between STK11/KEAP1 mutations and blood-based tumor mutational burden (bTMB)/PD-L1 expression. Univariate and multivariate Cox regression hazard models were preformed to analyze the influence of prognostic factors on survival. Survival difference was compared by Kaplan-Meier and log-rank test.

Results: Most STK11/KEAP1 mutations (7.33 %/10.76 %) were found in non-squamous NSCLC compared with squamous lung cancer. Interestingly, only 1.56 % STK11 mutation or 3.13 % KEAP1 mutation occurred in EGFR mutant non-squamous NSCLC. Compared with wild type, patients with STK11/KEAP1 mutations had higher bTMB (both, P < 0.001). Moreover, compared with wild type, patients harbored KEAP1 mutation had higher PD-L1 expression (TC3/IC3: 25.00 % vs. 14.54 %), while patients harbored STK11 mutation had lower PD-L1 expression (TC3/IC3: 7.89 % vs. 15.90 %). Univariate and multivariate analyses revealed that STK11/KEAP1 mutations were independent and significant prognostic factors on overall survival (OS) (both, P < 0.05) and progression-free survival (PFS) (both, P < 0.05). Importantly, patients harbored STK11/KEAP1 mutations had a relatively worse OS than wild type both in those receiving atezolizumab and docetaxel (all, P < 0.05). In addition, for STK11 mutant subset, atezolizumab did not improve OS compared with docetaxel (HR = 0.669; 95 %CI: 0.380-1.179; P = 0.669); while cox-regression analysis showed the improved survival of patients with KEAP1 mutation who receiving atezolizumab compared with docetaxel (HR = 0.610; 95 %CI: 0.384-0.969; P = 0.036).

Conclusion: Compared with wild type, non-squamous NSCLC patients with STK11/KEAP1 mutations may not benefit more from both atezolizumab and docetaxel. However, patients with mere KEAP1 mutations and without STK11 mutations may have a better response to atezolizumab than docetaxel.
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http://dx.doi.org/10.1016/j.lungcan.2021.02.010DOI Listing
April 2021

Estrogen Receptor 1 Expression Patterns Have Different Effects on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors' Treatment Response in Epidermal Growth Factor Receptor Mutant Lung Adenocarcinoma.

Front Oncol 2020 29;10:603883. Epub 2021 Jan 29.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Estrogen receptor (ER) can regulate cellular signaling through non-genomic mechanisms, potentially promoting resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanisms underlying the ER-mediated resistance to EGFR TKIs remain poorly understood. In this study, we investigated the role of the interaction between ER1 and ER5 in non-genomic signaling in lung adenocarcinoma. We established PC9 cell lines stably overexpressing ER1 or ER1/ER5. Immunofluorescence revealed that ER5 overexpression partly retained ER1 in the cytoplasm. Immunoblotting analyses revealed that EGFR pathway activation levels were higher in PC9/ER1/5 cells than those in PC9/ER1 or control PC9 cells. In the presence of estradiol, PI3K/AKT/mTOR pathway activation levels were higher in ER1/5-expressing cells than those in ER1-expressing cells. Additionally, PC9/ER1/5 cells were less prone to the cytotoxic and pro-apoptotic effects of gefitinib compared with PC9/ER1 or control PC9 cells. Cytoplasmic ER1 was associated with poor progression-free survival in lung cancer patients treated with EGFR TKIs. These results suggest that cytoplasmic ER1 was responsible for EGFR TKI resistance slightly through non-genomic mechanism in EGFR mutant lung adenocarcinoma.
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http://dx.doi.org/10.3389/fonc.2020.603883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879979PMC
January 2021

A Novel Nomogram Model Based on Cone-Beam CT Radiomics Analysis Technology for Predicting Radiation Pneumonitis in Esophageal Cancer Patients Undergoing Radiotherapy.

Front Oncol 2020 17;10:596013. Epub 2020 Dec 17.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Purpose: We quantitatively analyzed the characteristics of cone-beam computed tomography (CBCT) radiomics in different periods during radiotherapy (RT) and then built a novel nomogram model integrating clinical features and dosimetric parameters for predicting radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC).

Methods: At our institute, a retrospective study was conducted on 96 ESCC patients for whom we had complete clinical feature and dosimetric parameter data. CBCT images of each patient in three different periods of RT were obtained, the images were segmented using both lungs as the region of interest (ROI), and 851 image features were extracted. The least absolute shrinkage selection operator (LASSO) was applied to identify candidate radiomics features, and logistic regression analyses were applied to construct the rad-score. The optimal period for the rad-score, clinical features, and dosimetric parameters were selected to construct the nomogram model and then the receiver operating characteristic (ROC) curve was used to evaluate the prediction capacity of the model. Calibration curves and decision curves were used to demonstrate the discriminatory and clinical benefit ratios, respectively.

Results: The relative volume of total lung treated with ≥5 Gy (V5), mean lung dose (MLD), and tumor stage were independent predictors of RP and were finally incorporated into the nomogram. When the three time periods were modeled, the first period was better than the others. In the primary cohort, the area under the ROC curve (AUC) was 0.700 (95% confidence interval (CI) 0.568-0.832), and in the independent validation cohort, the AUC was 0.765 (95% CI 0.588-0.941). In the nomogram model that integrates clinical features and dosimetric parameters, the AUC in the primary cohort was 0.836 (95% CI 0.700-0.918), and the AUC in the validation cohort was 0.905 (95% CI 0.799-1.000). The nomogram model exhibits excellent performance. Calibration curves indicate a favorable consistency between the nomogram prediction and the actual outcomes. The decision curve exhibits satisfactory clinical utility.

Conclusion: The radiomics model based on early lung CBCT is a potentially valuable tool for predicting RP. V5, MLD, and tumor stage have certain predictive effects for RP. The developed nomogram model has a better prediction ability than any of the other predictors and can be used as a quantitative model to predict RP.
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http://dx.doi.org/10.3389/fonc.2020.596013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774595PMC
December 2020

GINS2 attenuates the development of lung cancer by inhibiting the STAT signaling pathway.

J Cancer 2021 1;12(1):99-110. Epub 2021 Jan 1.

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 272173, China.

GINS complex subunit 2 (GINS2) controls DNA replication. GINS2 expression is upregulated in several kinds of aggressive tumors. However, the effect of GINS2 in lung cancer remains unclear. We performed TCGA database analysis to confirm the clinical significance of GINS2 in lung cancer. After silencing GINS2 in A549 cells, we performed MTT assays, flow cytometry assays, colony formation assays, cell cycle analyses and RNA sequence analysis to elucidate the effect of GINS2 on lung cancer. Moreover, we assessed tumor growth and analyzed body fluorescence in mice as a measure of tumor burden. The TCGA database analysis demonstrated that GINS2 mRNA and protein was highly expressed in three kinds of lung cancer tissues. Subsequently, knockdown of GINS2 inhibited cell proliferation, colony formation, cell cycle arrest and apoptosis in A549 cells. On the other hand, we also investigated the effect of GINS2 on tumor formation in vivo. The analysis of nude mouse tumors showed that the tumor volume and weight of shGINS2 mice were significantly smaller than those of the control mice. To reveal the mechanism of GINS2 in lung cancer, we collected A549 cells with GINS2 knockdown to examine the downstream gene expression changes. The results showed that STAT1 and STAT2 mRNA and protein expression were significantly upregulated after GINS2 knockdown in A549 cells. Our results suggest that GINS2 inhibits the proliferation of lung cancer cells by inhibiting the STAT signaling pathway, which may be a potential biomarker for the diagnosis or prognosis of lung cancer.
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http://dx.doi.org/10.7150/jca.46744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738824PMC
January 2021

Incorporating the Number of PLN into the AJCC Stage Could Better Predict the Survival for Patients with NSCLC: A Large Population-Based Study.

J Oncol 2020 11;2020:1087237. Epub 2020 Dec 11.

Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.

Purpose: This study aimed to investigate the application of the number of positive lymph nodes (PLNs) in tumor, node, metastasis (TNM) staging system of non-small cell lung cancer (NSCLC) patients. . We screened a total of 15820 patients with resected NSCLC between 2004 and 2015 from SEER database. The X-tile model was used to determine the cutoff values of the number of PLNs. Overall survival (OS) curves were plotted using the Kaplan-Meier method, and the differences among the individual groups were defined using the log-rank test. Cox regression model was used to perform univariate and multivariate analyses and to assess the association between the number of PLNs and OS.

Results: In this study, using the X-tile model, we screened three different cutoff values, including nN0, nN1-3, and nN4-. Survival curves demonstrated that our defined nN stage had a significant predictive value for OS ( < 0.001). In the univariate and multivariate Cox analyses, the result showed that nN stage was a significant prognostic factor of OS for NSCLC patients ( < 0.001). Subsequently, we classified the patients into five subgroups based on the combination of pN and nN stages, including pN0 + nN0, pN1 + nN1-3, pN2 + nN1-3, pN1 + nN4-, and pN2 + nN4-. Moreover, survival curves revealed significant differences among these five groups ( < 0.001).

Conclusion: A combination of pathological LNs (pN) and the number of LN (nN) involvement in NSCLC patients had a better prognostic value than the current TNM staging system based on only pN stage.
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http://dx.doi.org/10.1155/2020/1087237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748903PMC
December 2020

Corrigendum: Anlotinib Combined With Chemoradiotherapy Exhibits Significant Therapeutic Efficacy in Esophageal Squamous Cell Carcinoma.

Front Oncol 2020 20;10:583499. Epub 2020 Nov 20.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

[This corrects the article DOI: 10.3389/fonc.2020.00995.].
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http://dx.doi.org/10.3389/fonc.2020.583499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716789PMC
November 2020

Phytoplankton alpha diversity indices response the trophic state variation in hydrologically connected aquatic habitats in the Harbin Section of the Songhua River.

Sci Rep 2020 12 7;10(1):21337. Epub 2020 Dec 7.

College of Life Science and Technology, Harbin Normal University, Harbin, 150025, China.

The relationship between biodiversity and ecological functioning is a central issue in freshwater ecology, but how this relationship is influenced by hydrological connectivity stress is still unknown. In this study we analyzed the dynamic of the phytoplankton alpha diversity indices and their relationships with trophic state in two hydrologically connected aquatic habitats (Jinhewan Wetland and Harbin Section of the Songhua River) in the Songhua River Basin in northeast China. We hypothesized that the phytoplankton alpha-diversity indices have the potential to provide a signal linking trophic state variation in hydrologically connected aquatic habitats. Our results showed the Cyanophyta and Bacillariophyta were abundant at most stations. T-test showed that phytoplankton alpha diversity indices varied significantly between rainy season and dry season. Trophic State Index recorded that a meso-trophic to eutrophic states of two connected habits during study period. Multivariate statistical analysis revealed that the dynamic of phytoplankton alpha diversity index was closely associated with trophic states change. Our result indicated that hydrological connectivity is a key factor influenced phytoplankton community assembly. In addition, it is beneficial to develop an integrated approach to appropriately describe and measure the trophic state variations of hydrologically connected aquatic habits in freshwater ecosystem.
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http://dx.doi.org/10.1038/s41598-020-78300-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721905PMC
December 2020

Multiplex and optimization of dCas9-TV-mediated gene activation in plants.

J Integr Plant Biol 2021 Apr 11;63(4):634-645. Epub 2021 Feb 11.

Guangdong Provincial Key Laboratory of Plant Resources, State Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.

Synthetic gene activators consisting of nuclease-dead Cas9 (dCas9) for single-guide RNA (sgRNA)-directed promoter binding and a transcriptional activation domain (TAD) represent new tools for gene activation from endogenous genomic locus in basic and applied plant research. However, multiplex gene coactivation by dCas9-TADs has not been demonstrated in whole plants. There is also room to optimize the performance of these tools. Here, we report that our previously developed gene activator, dCas9-TV, could simultaneously upregulate OsGW7 and OsER1 in rice by up to 3,738 fold, with one sgRNA targeting to each promoter. The gene coactivation could persist to at least the fourth generation. Astonishingly, the polycistronic tRNA-sgRNA expression under the maize ubiquitin promoter, a Pol II promoter, could cause enormous activation of these genes by up to >40,000-fold in rice. Moreover, the yeast GCN4 coiled coil-mediated dCas9-TV dimerization appeared to be promising for enhancing gene activation. Finally, we successfully introduced a self-amplification loop for dCas9-TV expression in Arabidopsis to promote the transcriptional upregulation of AtFLS2, a previously characterized dCas9-TV-refractory gene with considerable basal expression. Collectively, this work illustrates the robustness of dCas9-TV in multigene coactivation and provides broadly useful strategies for boosting transcriptional activation efficacy of dCas9-TADs in plants.
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http://dx.doi.org/10.1111/jipb.13023DOI Listing
April 2021

A fluorescence sensing method for brilliant blue with gold nanoclusters based on the inner filter effect.

Anal Methods 2020 10 1;12(37):4551-4555. Epub 2020 Sep 1.

Shandong Peninsula Engineering Research Center of Comprehensive Brine Utilization, Weifang University of Science and Technology, Shouguang, 262700 Weifang, China.

Due to the inner filter effect (IFE) between Brilliant Blue (BB) and gold nanoclusters (AuNCs), a simple and rapid approach for BB detection was developed. Since the absorption spectrum of BB has a good overlap with the emission spectrum of the AuNCs, the fluorescence of the AuNC solution was quenched after adding BB. Under optimal conditions, a good linear relationship for detection of BB was obtained from 0.05 to 7.5 μM, and the detection limit was 0.0167 μM. More importantly, the assay was successfully applied to assess BB in food samples such as hard candy, chocolate and dried blueberries, showing its potential in food quality control in the future.
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http://dx.doi.org/10.1039/d0ay01355bDOI Listing
October 2020

CMTM6 is positively correlated with PD-L1 expression and immune cells infiltration in lung squamous carcinoma.

Int Immunopharmacol 2020 Nov 28;88:106864. Epub 2020 Aug 28.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China. Electronic address:

Background: The aim of this study was to clarify the association between CMTM6 and PD-L1 expression as well as microenvironment in lung squamous carcinoma (LUSC).

Material And Methods: Using Spearman's correlation and Tumor Immune Estimation Resource (TIMER), we analyzed the relationship between CMTM6 and PD-L1 mRNA in LUSC. Immunohistochemistry (IHC) assay was applied to validate the correlation between CMTM6 and PD-L1 protein level in 80 LUSC samples originated from Shandong Provincial Hospital. Then, using The Cancer Genome Atlas (TCGA) database and fisher test, we analyzed the differential mutation genes in high and low CMTM6 expression group. TISIDB was used to explore the distribution of CMTM6 across immune- and molecular-subtypes. TCGA database and Gene Set variation analysis (GSVA) were used to analyze the relationship between CMTM6 and immune genes, immune related pathways.

Result: Positive correlation between CMTM6 and PD-L1 in mRNA and protein level was found in LUSC patients. More gene mutations were found in CMTM6 high expression group compared with low expression group. Meanwhile, we also found the correlation between CMTM6 expression and molecular subtypes, immune genes, immune related pathways. Furthermore, our result revealed that B cells memory, T cells memory testing, T cells folicular helper, macrophages M0, macrophages M1 and neutrophils varied significantly between patients with CMTM6 high and low expression group. Finally, we found that CMTM6 expression was positively related to CD8 + T cell, macrophage, neutrophil and dendtritic cell (all, P < 0.05) and negatively related to CD4 + T cell (P = 0.018).

Conclusion: CMTM6 is positively associated with PD-L1 expression and correlates with infiltration of immune cells in microenvironment of lung squamous carcinoma.
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http://dx.doi.org/10.1016/j.intimp.2020.106864DOI Listing
November 2020

Anlotinib Combined With Chemoradiotherapy Exhibits Significant Therapeutic Efficacy in Esophageal Squamous Cell Carcinoma.

Front Oncol 2020 10;10:995. Epub 2020 Jul 10.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

The aim of this study was to evaluate the safety and efficacy of anlotinib combined with chemoradiotherapy for treating esophageal squamous cell carcinoma (ESCC) using patient-derived xenografts (PDXs). PDX-bearing mice were randomly divided into five groups, as follows: control group receiving normal saline, the group receiving radiotherapy, the group receiving cisplatin combined with radiotherapy, the group receiving anlotinib combined with radiotherapy, and the group receiving anlotinib, and cisplatin combined with radiotherapy. Tumor volumes and body weights were measured three times weekly for 2 weeks. The PDXs were initially assessed by comparing the histology of the original patient tumor tissues with that of the corresponding serially passaged xenografts by hematoxylin and eosin (H&E) and P63 staining. Then, expression of Bax, c-PARP, PCNA, and CD31 was detected using immunohistochemistry, and apoptosis was detected by a TUNEL assay. Cytokines released into plasma were analyzed using protein chip technology. Finally, two case studies of ESCC patients were presented to further verify the results observed in the PDX models. The pathological characteristics of the serially passaged patient tumor-derived xenografts established in our study were in line with those of the original ESCC patient samples. The group receiving anlotinib and cisplatin plus radiotherapy exhibited the strongest antitumor response among the groups. Moreover, the ideal anticancer effects of anlotinib combined with chemoradiotherapy observed in clinical patients were consistent with the results observed in the PDX models, and no serious side effects were observed during treatment. Combination therapy with anlotinib and chemoradiotherapy may be an effective regimen for the treatment of advanced ESCC.
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http://dx.doi.org/10.3389/fonc.2020.00995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365939PMC
July 2020

Tumor Primary Location May Affect Metastasis Pattern for Patients with Stage IV NSCLC: A Population-Based Study.

J Oncol 2020 9;2020:4784701. Epub 2020 Jul 9.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.

Background: Most patients with nonsmall cell lung cancer (NSCLC) were initially diagnosed with distant metastasis. At present, there is no study to clarify the correlation between the primary location of the tumor and the metastasis pattern in advanced NSCLC. So we conducted this study to explored the relationship between the tumor primary location and metastasis pattern in stage IV NSCLC.

Methods: A total of 19,295 eligible patients were identified from 2010 to 2012 in the SEER database. The main endpoint of our study was overall survival (OS). The survival curves were created by using the Kaplan-Meier method and compared by the usage of the Log Rank test. The clinical variable characteristics were compared by the chi-square test, and multivariate logistic regression analyses were used to evaluate the risk factors on metastasis patterns. All statistical values were two-sided, and it was considered statistically significant when ≤ 0.05.

Results: We found that different proportions of metastatic sites could be found in different tumor primary locations. In addition, the prognosis of lung metastasis was relatively good in patients with tumor location in main bronchus ( < 0.001), upper lobe ( < 0.001), lower lobe ( < 0.001) , and middle lobe ( = 0.005). Besides, there was no significant OS difference for patients whose primary location was overlapping lesion ( = 0.226). The results also demonstrated that compared with patients with primary tumor located in the main bronchus, those in the upper lobe were more likely to have brain metastasis ( = 0.01) and lung metastasis ( = 0.024), those in the middle lobe were more prone to develop lung metastasis ( = 0.035) and those in the lower lobe were more apt to cause bone metastasis ( = 0.005) and lung metastasis ( = 0.001). In addition, there was no statistical difference in metastasis patterns among patients with overlapping lesions ( > 0.05).

Conclusions: Different primary tumor locations might affect the metastasis pattern in patients with stage IV NSCLC.
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http://dx.doi.org/10.1155/2020/4784701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368215PMC
July 2020

Comprehensive analysis of multiple parameters associated with tumor immune microenvironment in mutant cancers.

Future Oncol 2020 Oct 8;16(29):2295-2306. Epub 2020 Jul 8.

Department of Medical Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China.

To verify the relationship between and tumor immune microenvironment thus immune checkpoint inhibitors (ICIs) response. Several public databases were used to characterize the association between gene alteration and tumor immunity. The gene mutation frequency was 8.2% in all cancer types. The -mutated cancers have higher scores of mutation count, tumor mutational burden, neoantigen load (p < 0.001) and T cell repertoire, B cell repertoire diversity (p < 0.05). The gene mutation has tight association with multiple-activated immune cells. Survival analysis suggested that patients with mutant cancers benefit more from ICIs treatment (p = 0.013). The gene mutation was correlated with higher tumor immunogenicity and activated antitumor immune microenvironment, resulting in superior cohort that respond well to ICIs.
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http://dx.doi.org/10.2217/fon-2020-0243DOI Listing
October 2020

A Novel Nomogram including AJCC Stages Could Better Predict Survival for NSCLC Patients Who Underwent Surgery: A Large Population-Based Study.

J Oncol 2020 20;2020:7863984. Epub 2020 May 20.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.

Objective: In this study, we aimed to establish a novel nomogram model which was better than the current American Joint Committee on Cancer (AJCC) stage to predict survival for non-small-cell lung cancer (NSCLC) patients who underwent surgery. . 19617 patients with initially diagnosed NSCLC were screened from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2015. These patients were randomly divided into two groups including the training cohort and the validation cohort. The Cox proportional hazard model was used to analyze the influence of different variables on overall survival (OS). Then, using R software version 3.4.3, we constructed a nomogram and a risk classification system combined with some clinical parameters. We visualized the regression equation by nomogram after obtaining the regression coefficient in multivariate analysis. The concordance index (C-index) and calibration curve were used to perform the validation of nomogram. Receiver operating characteristic (ROC) curves were used to evaluate the clinical utility of the nomogram.

Results: Univariate and multivariate analyses demonstrated that seven factors including age, sex, stage, histology, surgery, and positive lymph nodes (all, < 0.001) were independent predictors of OS. Among them, stage (C-index = 0.615), positive lymph nodes (C-index = 0.574), histology (C-index = 0.566), age (C-index = 0.563), and sex (C-index = 0.562) had a relatively strong ability to predict the OS. Based on these factors, we established and validated the predictive model by nomogram. The calibration curves showed good consistency between the actual OS and predicted OS. And the decision curves showed great clinical usefulness of the nomogram. Then, we built a risk classification system and divided NSCLC patients into two groups including high-risk group and low-risk group. The Kaplan-Meier curves revealed that OS in the two groups was accurately differentiated in the training cohort ( < 0.001). And then, we validated this result in the validation cohort which also showed that patients in the high-risk group had worse survival than those in the low-risk group.

Conclusion: The results proved that the nomogram model had better performance to predict survival for NSCLC patients who underwent surgery than AJCC stage. These tools may be helpful for clinicians to evaluate prognostic indicators of patients undergoing operation.
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http://dx.doi.org/10.1155/2020/7863984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256774PMC
May 2020

Therapeutic effects of Co-Venenum Bufonis Oral Liquid on radiation-induced esophagitis in rats.

Exp Anim 2020 Aug 10;69(3):354-362. Epub 2020 Apr 10.

Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Jinan, Shandong 250017, P.R.China.

To investigate the effects of Co-Venenum Bufonis Oral Liquid (cVBOL) on radiation-induced esophagitis in rats. Irradiation (30 Gy) with X-RAD 225 x-ray was applied to induce esophagitis in 64 Wistar rats and treated by different methods. The body weight of rats either in RT group, cVBOL+RT, or EM+RT group was significantly decreased when compared with that in normal group (P<0.0001). After irradiation, histopathological studies, immunohistochemistry, and MRI scanning on esophagus were performed. Serum TNF-α,IL-6 and IL-10 were also determined by ELISA at 7, 14, 21 and 28 days after radiation treatment. The results demonstrated that radiation caused esophageal injury and thickening of esophageal tissue layers. The esophageal tissues after radiation treatment showed typical pathological changes of esophagitis. Radiation also caused esophagus edema. Treatment of cVBOL reduced the severity of histological esophageal lesion, decreased the expression of bFGF and TGF-β1, and lowered serum levels of inflammatory cytokines including TNF-α, IL-6 and IL-10 over 28 days after radiation treatment. In conclusion, cVBOL treatment is effective to prevent radiation induced esophagitis and reduces radiation induced esophagitis may be mediated through its ant-inflammatory effects.
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http://dx.doi.org/10.1538/expanim.19-0142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445061PMC
August 2020

Differences in Stage of Cancer at Diagnosis, Treatment, and Survival by Race and Ethnicity Among Leading Cancer Types.

JAMA Netw Open 2020 04 1;3(4):e202950. Epub 2020 Apr 1.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Importance: Information about stage of cancer at diagnosis, use of therapy, and survival among patients from different racial/ethnic groups with 1 of the most common cancers is lacking.

Objective: To assess stage of cancer at diagnosis, use of therapy, overall survival (OS), and cancer-specific survival (CSS) in patients with cancer from different racial/ethnic groups.

Design, Setting, And Participants: This cohort study included 950 377 Asian, black, white, and Hispanic patients who were diagnosed with prostate, ovarian, breast, stomach, pancreatic, lung, liver, esophageal, or colorectal cancers from January 2004 to December 2010. Data were collected using the Surveillance, Epidemiology, and End Results (SEER) database, and patients were observed for more than 5 years. Data analysis was conducted in July 2018.

Main Outcomes And Measures: Multivariable logistic and Cox regression were used to evaluate the differences in stage of cancer at diagnosis, treatment, and survival among patients from different racial/ethnic groups.

Results: A total of 950 377 patients (499 070 [52.5%] men) were included in the study, with 681 251 white patients (71.7%; mean [SD] age, 65 [12] years), 116 015 black patients (12.2%; mean [SD] age, 62 [12] years), 65 718 Asian patients (6.9%; mean [SD] age, 63 [13] years), and 87 393 Hispanic patients (9.2%; mean [SD] age, 61 [13] years). Compared with Asian patients, black patients were more likely to have metastatic disease at diagnosis (odds ratio [OR], 1.144; 95% CI, 1.109-1.180; P < .001). Black and Hispanic patients were less likely to receive definitive treatment than Asian patients (black: adjusted OR, 0.630; 95% CI, 0.609-0.653; P < .001; Hispanic: adjusted OR, 0.751; 95% CI, 0.724-0.780; P < .001). White, black, and Hispanic patients were more likely to have poorer CSS and OS than Asian patients (CSS, white: adjusted HR, 1.310; 95% CI, 1.283-1.338; P < .001; black: adjusted HR, 1.645; 95% CI, 1.605-1.685; P < .001; Hispanic: adjusted HR, 1.300; 95% CI, 1.266-1.334; P < .001; OS, white: adjusted HR, 1.333; 95% CI, 1.310-1.357; P < .001; black: adjusted HR, 1.754; 95% CI, 1.719-1.789; P < .001; Hispanic: adjusted HR, 1.279; 95% CI, 1.269-1.326; P < .001).

Conclusions And Relevance: In this study of patients with 1 of 9 leading cancers, stage at diagnosis, treatment, and survival were different by race and ethnicity. These findings may help to optimize treatment and improve outcomes.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.2950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142383PMC
April 2020

Radiotherapy may improve survival of ES-SCLC with distant metastasis only for patients with one metastatic site: A population-based study.

Oncol Lett 2020 Jan 14;19(1):139-146. Epub 2019 Nov 14.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.

The aim of the present study was to investigate the prognostic impact of RT on patients with extensive stage small cell lung cancer (ES-SCLC) and distant metastasis. Using the Surveillance Epidemiology and End Results (SEER) database, 8,595 patients with ES-SCLC exhibiting distant metastasis treated between 2010 and 2013 were identified. Patient baseline characteristics were compared using the χ test. The Kaplan-Meier test was used to analyze subgroup cancer-specific survival (CSS) rate, and differences were compared using a log-rank test. Univariate and multivariate Cox regression models were used to analyze the prognostic variables on CSS. RT was determined to be an independent prognostic factor for patient CSS (P<0.001). In addition, RT could improve the CSS of patients with ES-SCLC with one metastatic lesion (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68; P<0.001), including the bone, brain, liver and lung metastatic sites. However, for patients with two metastatic sites, RT did not improve CSS regardless of metastasis pattern (all P>0.05). To conclude, RT may improve the survival rate of patients with ES-SCLC with distant metastasis, particularly in those with only one metastatic site.
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http://dx.doi.org/10.3892/ol.2019.11092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923894PMC
January 2020

Different distant metastasis patterns based on tumor size could be found in extensive-stage small cell lung cancer patients: a large, population-based SEER study.

PeerJ 2019 3;7:e8163. Epub 2019 Dec 3.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Background: Small-cell lung cancer (SCLC) is a malignant cancer with the ability to metastasize quickly. The relationship between tumor size and the distant metastasis patterns of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) has not been reported.

Objectives: The aim of this study was to determine the different distant metastasis patterns as they related to tumor size in ES-SCLC.

Patients And Methods: We used Surveillance, Epidemiology, and End Results (SEER) population-based data collected from 2010 through 2013 to identify 11058 ES-SCLC patients with definite evidence of distant metastases. Multivariate logistic regression analysis was used to demonstrate the association between tumor size and distant metastasis patterns including bone, liver, brain, and lung metastases. Age, race, sex, and N stage were also selected in the logistic regression model.

Results: Subtle differences in metastasis patterns were found among patients based on different tumor sizes. Patients with tumors 3-7 cm have a higher risk of bone metastasis compared with those that have tumors ≤3 cm (OR 1.165, 95% CI [1.055-1.287],  = 0.003) and patients with tumors ≥7 cm have a higher risk of lung metastasis (OR 1.183, 95% CI [1.039-1.347],  = 0.011). In addition, patients with tumors ≥7 cm had a lower risk of brain metastasis and liver metastasis than patients with tumors ≤3 cm (OR 0.799, 95% CI [0.709-0.901],  < 0.001; OR 0.747, 95% CI [0.672-0.830],  < 0.001). Interestingly, there was no correlation between a larger tumor and a higher risk of metastasis. However, the tumor metastasis pattern did have some correlation with age, gender, race and N-status.

Conclusion: The pattern of distant metastasis of ES-SCLC is related to the tumor size and the tumor size is indicative of the metastatic site. Larger tumor sizes did not correlate with a higher risk of distant metastasis, but the size is related to the pattern of distant metastasis. The study of different distant metastasis patterns based on tumor size and other clinical features (e.g., age, race, sex, and N stage) in ES-SCLC is clinically valuable.
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http://dx.doi.org/10.7717/peerj.8163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896937PMC
December 2019

Genome-wide identification and expression analysis of the gene family in soybean ().

PeerJ 2019 21;7:e7509. Epub 2019 Aug 21.

Key Laboratory of Soybean Biology in Chinese Ministry of Education, Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry, Northeast Agricultural University, Harbin, Heilongjiang, China.

Background: VQ proteins, the plant-specific transcription factors, are involved in plant development and multiple stresses; however, only few articles systematic reported the genes in soybean.

Methods: In total, we identified 75 genes, which were classified into 7 groups (I-VII). Conserved domain analysis indicated that gene family members all contain the domains. genes from the same evolutionary branches of soybean shared similar motifs and structures. Promoter analysis revealed that -elements related to stress responses, phytohormone responses and controlling physical as well as reproductive growth. Based on the RNA-seq and qRT-PCR analysis, genes were showed expressing in nine tissues, suggesting their putative function in many aspects of plant growth and development as well as response to stress in .

Results: This study aims to understand the roles of genes in various development processes and their expression patterns in responses to stimuli. Our results provide basic information in identification and classification of genes. Further experimental analysis will allows us to know the functions of participation in plant growth and stress responses.
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http://dx.doi.org/10.7717/peerj.7509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708371PMC
August 2019

A prognostic scoring model to determine which patients with metastatic extensive-stage small cell lung cancer could benefit from local radiotherapy: a large population-based study.

Discov Med 2019 06;27(150):255-265

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.

Objective: Our study was performed to clarify which patients with metastatic extensive-stage small cell lung cancer (ES-SCLC) could gain survival benefit from local radiotherapy.

Patients And Methods: A chi-square test was used to compare baseline characteristics of different groups. Kaplan-Meier method was applied to analyzing the survival difference. The prognostic factors for cancer-specific survival (CSS) in patients receiving radiotherapy were analyzed by the Cox proportional hazard model. According to the above information, we established a prognostic score model. Based on the prognostic score model, the Kaplan-Meier method was used to make survival curves to find the difference in prognosis. CSS based on different subgroup variables were analyzed by the Cox proportional hazard model and concrete results were shown in forest plots.

Results: Our study revealed that CSS improved in the radiotherapy group compared with the control/none group (P<0.001). The multivariate analysis identified that both female and metastasis number=1 as significant prognostic factors for favorable CSS. We established a prognostic score (PS) model with a score of 0 to 2. Based on the prognostic score model, survival curves were made and showed that CSS of the radiotherapy group improved significantly with the decreasing patient propensity score (P<0.001). In subgroup analyses, patients with PS=0 (P<0.001) and PS=1 (P<0.001) could benefit from receiving local radiotherapy; patients with PS=2 (P=0.160) demonstrated no significant difference in CSS after receiving local radiotherapy.

Conclusions: Local radiotherapy could improve the CSS of patients with metastatic ES-SCLC, only for patients with a 0-1 score.
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June 2019

Poor survival of non-small-cell lung cancer patients with main bronchus tumor: a large population-based study.

Future Oncol 2019 Aug 8;15(24):2819-2827. Epub 2019 Aug 8.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China.

In this study, we evaluated the association between tumor location and prognosis in non-small-cell lung cancer patients. The SEER database was used to screen for suitable patients using our inclusion criteria. The χ test was used to compare baseline patient characteristics and the Kaplan-Meier method as well as the log-rank test were used to compare survival differences. At last, univariate and multivariate Cox proportional hazards regression models were used to analyze the influence of different variables on overall survival. The results found no significant difference in overall survival between patients in laterality (p = 0.071). However, patients with main bronchial tumors had worse prognosis than tumors at other locations (p < 0.001). Our results also showed that tumor location including main bronchus, upper lobe, middle lobe, lower lobe and overlapping lesion was a significant factor affecting survival (p < 0.001). Subgroup analysis revealed that regardless of histology or M stage, patients with main bronchial tumors had a worse survival compared with other tumor locations (all; p < 0.001). Interestingly, we found that patients with tumor main bronchial tumors were more likely to be squamous carcinoma and terminal Tumor, Node, Metastasis stage (all; p < 0.001). Non-small-cell lung cancer patients' prognosis was related to the tumor location. And patients with tumors located in main bronchus had worse outcomes than those located in other locations. Tumor primary site should be considered in treatment management and prognosis assessment.
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http://dx.doi.org/10.2217/fon-2019-0098DOI Listing
August 2019

Targeted Transcriptional Activation in Plants Using a Potent Dead Cas9-Derived Synthetic Gene Activator.

Curr Protoc Mol Biol 2019 06;127(1):e89

Guangdong Provincial Key Laboratory of Plant Resources, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Genetic tools for specific perturbation of endogenous gene expression are highly desirable for interrogation of plant gene functions and improvement of crop traits. Synthetic transcriptional activators derived from the CRISPR/Cas9 system are emerging as powerful new tools for activating the endogenous expression of genes of interest in plants. These synthetic constructs, generated by tethering transcriptional activation domains to a nuclease-dead Cas9 (dCas9), can be directed to the promoters of endogenous target genes by single guide RNAs (sgRNAs) to activate transcription. Here, we provide a detailed protocol for targeted transcriptional activation in plants using a recently developed, highly potent dCas9 gene activator construct referred to as dCas9-TV. This protocol covers selection of sgRNA targets, construction of sgRNA expression cassettes, and screening for an optimal sgRNA using a protoplast-based promoter-luciferase assay. Finally, the dCas9-TV gene activator coupled with the optimal sgRNA is delivered into plants via Agrobacterium-mediated transformation, thereby enabling robust upregulation of target gene expression in transgenic Arabidopsis and rice plants. © 2019 by John Wiley & Sons, Inc.
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http://dx.doi.org/10.1002/cpmb.89DOI Listing
June 2019

Astragaloside IV alleviates doxorubicin induced cardiomyopathy by inhibiting NADPH oxidase derived oxidative stress.

Eur J Pharmacol 2019 Sep 21;859:172490. Epub 2019 Jun 21.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China. Electronic address:

Doxorubicin (DOX) is a classic anti-tumor chemotherapeutic used to treat a wide range of tumors. One major downfall of DOX treatment is it can induce fatal cardiotoxicity. Astragaloside IV (AS-IV) is one of the primary active ingredients that can be isolated from the traditional Chinese herbal medicine, Astragalus membranaceus. This study uses both in vitro and in vivo tools to investigate whether AS-IV alleviates DOX induced cardiomyopathy. We found that AS-IV supplementation alleviates body weight loss, myocardial injury, apoptosis of cardiomyocytes, cardiac fibrosis and cardiac dysfunction in DOX-treated mice. Also, DOX-induced cardiomyocyte injury and apoptosis were effectively improved by AS-IV treatment in vitro. NADPH oxidase (NOX) plays an important role in the progress of the oxidative signal transduction and DOX-induced cardiomyopathy. In this study, we found that AS-IV treatment relieves DOX-induced NOX2 and NOX4 expression and oxidative stress in cardiomyocytes. In conclusion, AS-IV, an antioxidant, attenuates DOX-induced cardiomyopathy through the suppression of NOX2 and NOX4.
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http://dx.doi.org/10.1016/j.ejphar.2019.172490DOI Listing
September 2019

A hypothesized TNM staging system based on the number and location of positive lymph nodes may better reflect the prognosis for patients with NSCLC.

BMC Cancer 2019 Jun 17;19(1):591. Epub 2019 Jun 17.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.

Background: This study aimed to evaluate the feasibility and prognostic accuracy of incorporating the number of positive lymph nodes (PLN) into the TNM staging system for non-small cell lung cancer (NSCLC) patients.

Methods: We screened a total of 9539 patients with resected stage IA-IIIB non-small cell cancer between 2010 and 2015 from SEER database. The chi-square test was used to compare patient baseline characteristics and the X-tile model was applied to determine cut-off values for the number of PLN (nN). The X-tile model was used to screen three different cut-off values including nN = 0, nN1-3 and nN4-. Univariate and multivariate Cox proportional hazards regression models were used to analyze the influence of different variables on overall survival (OS). Kaplan-Meier and log-rank test were used to compare survival differences.

Results: Based on the nN cutoffs, we conducted the univariate and multivariate Cox proportional hazards regression. The result showed that nN stage was a significant prognostic factor affecting patients' OS (all P <  0.001). We reclassified the seventh edition TNM stages of the enrolled patients with stage IA-IIIB NSCLC according to the 5-year OS rate. Hypothesized TNM substage based on the location and the number of PLN was further calculated. Then we drew survival curves for each substage, including for the current TNM stage and the hypothesized TNM stage. From the comparison of survival curves, we found that the survival curve of each substage of the hypothesized TNM classification was proportional and well distributed compared with the current TNM classification (P <  0.001).

Conclusion: Revised TNM staging integrating locational pN stage and numerical nN stage was a more accurate prognostic determinant in patients with NSCLC.
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http://dx.doi.org/10.1186/s12885-019-5797-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580546PMC
June 2019

Gene disruption through base editing-induced messenger RNA missplicing in plants.

New Phytol 2019 04 24;222(2):1139-1148. Epub 2019 Jan 24.

Guangdong Provincial Key Laboratory of Plant Resources, State Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.

Gene knockout tools are highly desirable for basic and applied plant research. Here, we leverage the Cas9-derived cytosine base editor to introduce precise C-to-T mutations to disrupt the highly conserved intron donor site GT or acceptor site AG, thereby inducing messenger RNA (mRNA) missplicing and gene disruption. As proof of concept, we successfully obtained Arabidopsis null mutant of MTA gene in the T generation and rice double null mutant of GL1-1 and NAL1 genes in the T generation by this strategy. Elimination of the original intron donor site or acceptor site could trigger aberrant splicing at a new specific exonic site, but not at the closest GT or AG site, suggesting cryptic rules governing splice site recognition. The strategy presented expands the applications of base editing technologies in plants by providing a new means for gene inactivation without generating DNA double-strand breaks, and it can potentially serve as a useful tool for studying the biology of mRNA splicing.
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http://dx.doi.org/10.1111/nph.15647DOI Listing
April 2019

New cytosine base editor for plant genome editing.

Sci China Life Sci 2018 12 11;61(12):1602-1603. Epub 2018 Nov 11.

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.

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http://dx.doi.org/10.1007/s11427-018-9416-yDOI Listing
December 2018