Single-cell hdWGCNA reveals metastatic protective macrophages and development of deep learning model in uveal melanoma.

BACKGROUND: Although there has been some progress in the treatment of primary uveal melanoma (UVM), distant metastasis remains the leading cause of death in patients. Monitoring, staging, and treatment of metastatic disease have not yet reached consensus. Although more than half of metastatic tumors (62%) are diagnosed within five years after primary tumor treatment, the remainder are only detected in the following 25 years. The mechanisms of UVM metastasis and its impact on prognosis are not yet fully understood. METHODS: scRNA-seq data of UVM samples were obtained and processed, followed by cell type identification and characterization of macrophage subpopulations. High-dimensional weighted gene co-expression network analysis (HdWGCNA) was performed to identify key gene modules associated with metastatic protective macrophages (MPMφ) in primary samples, and functional analyses were conducted. Non-negative matrix factorization (NMF) clustering and immune cell infiltration analyses were performed using the MPMφ gene signatures. Machine learning models were developed using the identified metastatic protective macrophages related genes (MPMRGs) to distinguish primary from metastatic patients. A deep learning convolutional neural network (CNN) model was constructed based on MPMRGs and cell type associations. Lastly, a prognostic model was established using the MPMRGs and validated in independent cohorts. RESULTS: Single-cell RNA-seq analysis revealed a unique immune microenvironment landscape in primary samples compared to metastatic samples, with an enrichment of macrophage cells. Using HdWGCNA, MPMφ and marker genes were identified. Functional analysis showed an enrichment of genes related to antigen processing progress and immune response. Machine learning and deep learning models based on key genes showed significant effectiveness in distinguishing between primary and metastatic patients. The prognostic model based on key genes demonstrated substantial predictive value for the survival of UVM patients. CONCLUSION: Our study identified key macrophage subpopulations related to metastatic samples, which have a profound impact on shaping the tumor immune microenvironment. A prognostic model based on macrophage cell genes can be used to predict the prognosis of UVM patients.

Impact of separate concentrations of polyethylene microplastics on the ability of pollutants removal during the operation of constructed wetland-microbial fuel cell.

Microplastics (MPs) in water pose a great threat to the ecological environment, but the impact of MPs on constructed wetland microbial fuel cells (CW-MFCs) has not been studied, so in order to fill the research gap and enrich the research in the field of microplastics, a 360-day experiment was designed to determine the operating status of CW-MFCs at different concentrations (0, 10, 100 and 1000 µg/L) polyethylene microplastics (PE-MPs) at different times, focusing on the changes of the CW-MFCs' ability to handle pollutants, power production performance and microbial composition. The results showed that with the accumulation of PE-MPs, the removal effect of COD and TP did not change significantly, and that the removal rate was maintained at around 90% and 77.9% respectively, within 120 d of operation. What's more, the denitrification efficiency increased (from 4.1% to 19.6%), but with the passage of time, it decreased significantly (from 7.16% to 31.9%) at the end of the experiment, while oxygen mass transfer rate was significantly increased. Further analysis showed that the accumulation of PE-MPs did not affect the current power density significantly with the changes of time and concentration, but the accumulation of PE-MPs would inhibit the exogenous electrical biofilm and increase the internal resistance, thereby affecting the electrochemical performance of the system. In addition, the results of microbial PCA showed that the composition and the activity of the microorganisms were changed under the action of PE-MPs, that the microbial community in CW-MFC showed a dose effect on the input of PE-MPs, and that the relative abundance of nitrifying bacteria with time was significantly affected by PE-MPs concentration. The relative abundance of denitrifying bacteria decreased over time, but PE-MPs promoted the reproduction of denitrifying bacteria, which was consistent with the changes in nitrification and denitrification rates. The removal modes of EP-MPs by CW-MFC include the adsorption and the electrochemical degradation, with two isothermal adsorption models of Langmuir and Freundlich being constructed in the experiment, and the electrochemical degradation process of EP-MPs being simulated. In summary, the results show that the accumulation of PE-MPs can induce a series of changes in substrate, microbial species and activity of CW-MFCs, which in turn affects the pollutant removal efficiency and power generation performance during its operation.

Decomposition of Phosphorus Pollution and Microorganism Analysis Using Novel CW-MFCs under Different Influence Factors.

A constructed wetland (CW)-coupled microbial fuel cell (MFC) system was constructed to treat wastewater and generate electricity. The total phosphorus in the simulated domestic sewage was used as the treatment target, and the optimal phosphorus removal effect and electricity generation were determined by comparing the changes in substrates, hydraulic retention times, and microorganisms. The mechanism underlying phosphorus removal was also analyzed. By using magnesia and garnet as substrates, the best removal efficiencies of two CW-MFC systems reached 80.3% and 92.4%. Phosphorus removal by the garnet matrix mainly depends on a complex adsorption process, whereas the magnesia system relies on ion exchange reactions. The maximum output voltage and stabilization voltage of the garnet system were higher than those of the magnesia system. Microorganisms in the wetland sediments and electrode also changed considerably. It indicates that the mechanism of phosphorus removal by the substrate in the CW-MFC system is adsorption and chemical reaction between ions to generate precipitation. The population structure of proteobacteria and other microorganisms has an impact on both power generation and phosphorus removal. Combining the advantages of constructed wetlands and microbial fuel cells also improved phosphorus removal in coupled system. Therefore, when studying a CW-MFC system, the selection of electrode materials, matrix, and system structure should be taken into account to find a method that will improve the power generation capacity of the system and remove phosphorus.

A case presentation of patient from northern China with endomyocardial fibrosis.

BACKGROUND: Endomyocardial fibrosis (EMF) is a rare condition and a major cause of death in tropical countries. The etiology of EMF remains elusive, and no specific treatment has been developed yet, therefore it carries poor prognosis. CASE PRESENTATION: An 81-year-old male Chinese patient with a history of long-standing exertional breathlessness, presented with worsening symptoms rapidly evolving to orthopnea. A proper specific treatment was prescribed to the patient in the following days, including diuretics, angiotensin-converting-enzyme inhibitor and beta blockers. The patient died of progressive multiple organ failure. CONCLUSION: Echocardiography is technically limited due to the acoustic shadowing as a result of the calcification. Chest computed tomography is a more accurate diagnostic tool to examine the anatomic distribution and extent of endomyocardial calcification in this rare case.

Sex difference among patients with unprotected left main coronary artery disease undergoing percutaneous coronary intervention in northern China.

BACKGROUND: Unprotected left main coronary artery (ULMCA) disease is associated with high mortality and morbidity. The aim of this study is to investigate the efficacy of percutaneous coronary intervention (PCI) on gender-specific patients with ULMCA in the Chinese population and provide a basis for further treatment of PCI in ULMCA disease. METHODS: 173 patients (female, N = 52; male, N = 121; mean age = 61.02 ± 7.95) with ULMCA disease, who underwent PCI between January 2010 and December 2014, were investigated in our study. The mean follow-up time was 23.8 ± 7.3 months. The baseline clinical characteristics, coronary angiography (CAG) and PCI procedures, and in-hospital and follow-up outcomes of gender-specific patients were evaluated. RESULTS: There were no statistically significant differences in baseline clinical characteristics with the exception of body weight, height, and smoking indexes between women and men. During PCI procedure, femoral artery puncture was more preferred in women than men (P < .05), whereas radial artery puncture was more preferred in men than women (P < .05). The characteristics of CAG and PCI procedures (except puncture path) were showed with no markedly difference between women and men. The incidences of MACCEs in male patients during the in-hospital and follow-up periods were slightly higher than those of the female patients although with no statistical differences. CONCLUSION: In northern China, the incidence of ULMCA disease in men is likely to be higher than in women, whereas PCI for ULMCA disease shows similarly favorable outcomes in women as well as in men. During the PCI procedure, femoral artery puncture in women and radial artery puncture in men are recommended.

Study of coronary artery perforation during percutaneous coronary intervention in the Cangzhou Chinese population.

OBJECTIVE: Coronary artery perforation (CAP) is a rare, serious complication of percutaneous coronary intervention (PCI). Many studies have addressed the incidence, risk factors, and management of CAP in different countries except China. The aim of this study is to determine the risk factors and types of treatment for coronary perforation occurring in patients undergoing PCI and living in the Cangzhou Chinese population. METHODS AND RESULTS: A retrospective cohort of 12,113 patients who underwent PCI was used: 64 patients with CAP and 192 case-control patients were evaluated. Clinical data and findings from coronary arteriography and PCI were analysed. Logistic regression was used to evaluate candidate risk factors for CAP. The treatments were also evaluated. The incidence of CAP in patients undergoing PCI was 0.53%, and the mortality was 7.8% (5/64). Risk factors included female gender, hypertension, non-ST-elevation acute coronary syndrome (NSTE-ACS), right coronary artery (RCA) lesion, calcified lesion, and chronic total occlusion (CTO) (all P < 0.05, all OR > 1). CTO had the highest risk (OR = 5.077, P < 0.001). Patients with class I CAP underwent conservative treatment. Patients with class II CAP underwent conservative treatment or low-pressure balloon dilatation (61.1% and 22.2%, respectively). Patients with class III CAP underwent low-pressure balloon dilatation, coated-stent implantation, and emergency surgery (40.9%, 27.3%, and 22.7%, respectively). CONCLUSIONS: CAP risk factors in Cangzhou Chinese patients undergoing PCI included CTO, NSTE-ACS, hypertension, calcified and RCA lesions, and female gender. Different treatment methods should be used according to the different classes of CAP.

Knockdown of lncRNA SNHG16 attenuates myocardial ischemia­reoxygenation injury via targeting miR­183/FOXO1 axis.

Accumulating evidence shows that long non-coding RNAs (lncRNAs) are widely involved in cellular processes of myocardial ischemia/reperfusion (I/R). The present study investigated the functions of lncRNA SNHG16 in myocardial I/R and the mechanism mediated by SNHG16. The myocardial I/R rat and cell model and hypoxia/reoxygenation injury (H/R) models of H9C2 cardiomyocytes were established to detect the expression of SNHG16. Cell Counting Kit-8, flow cytometric and western blot assays were conducted to detect cell viability, apoptosis and protein expression. Myocardial cell apoptosis was assessed by TUNEL staining. Dual-luciferase gene reporter was applied to determine the interaction between the molecules. The expressions of SNHG16 were upregulated in myocardial I/R injury models. Inhibition of SNHG16 relieved myocardial I/R injury in vivo and in vitro silencing of SNHG16 alleviated H/R induced cardiomyocyte apoptosis. To explore the regulatory mechanism, it was discovered that SNHG16 directly interacted with miR-183, while forkhead box O1 (FoxO1) was a target of microRNA (miR)-183. Findings from rescue assays revealed that miR-183 inhibitor and upregulation of FOXO1 can rescue the effect of sh-SNHG16 on H/R-induced cardiomyocyte apoptosis. The results indicated that the lncRNA SNHG16/miR-183/FOXO1 axis exacerbated myocardial cell apoptosis in myocardial I/R injury, suggesting SNHG16 as a potential therapeutic target for myocardial I/R injury.

Pharmaceutical and personal care products (PPCPs) degradation and microbial characteristics of low-temperature operation combined with constructed wetlands.

Emerging contaminants (ECs), which are present in water bodies, could cause global environmental and human health problems. These contaminants originate from various sources such as hospitals, clinics, households, and industries. Additionally, they can also indirectly enter the water supply through runoff from agriculture and leachate from landfills. ECs, specifically Pharmaceutical and personal care products (PPCPs), are causing widespread concern due to their contribution to persistent water pollution. Traditional approaches often involve expensive chemicals and energy or result in the creation of by-products. This study developed a practical and environmentally-friendly method for removing PPCPs, which involved combining and integrating various techniques. To implement this method, it was necessary to establish and used a field simulator based on the real-life scenario. Based on the data analysis, the average removal rates of COD, TP, TN, and NH4+-N were 57%, 59%, 63%, and 73%, respectively. the removal rate of PPCPs by CCWs was found to be 82.7% after comparing samples that were not treated by constructed wetlands and those that were treated. Combined constructed wetlands (CCWs) were found to effectively remove PPCPs from water. This is due to the combined action of plant absorption, absorption, and biodegradation by microorganisms living in the wetlands. Interestingly, the wetland plant reed had been shown to play an important role in removing these pollutants. Microbial degradation was the most important pathway for PPCPs removal in CCWs. Carbamazepine was selected as a typical PPCP for analysis. In addition, the microbial community structure of the composite filler was also investigated. High-throughput sequencing confirmed that the dominant bacteria had good adaptability to PPCPs. This technique not only reduced the potential environmental impact but also served as a foundation for further research on the use of constructed wetlands for the treatment of PPCPs contaminated water bodies and its large-scale implementation.

MiR-1299 functions as a tumor suppressor to inhibit the proliferation and metastasis of gastric cancer by targeting ARF6.

BACKGROUND: MiRNAs belong to non-coding RNAs that are involved in cancer development. Acting as a mediator, they could regulate the expression level of numerous gens. However, the expression and function of miR-1299 in gastric cancer (GC) are not clear. OBJECTIVE: To explore the role of miR-1299 in the process of GC. METHODS: We detected the levels of miR-1299 in clinical samples of GC and investigated the role of miR-1299 in the regulation of the GC cells proliferation, apoptosis and metastasis. Luciferase reporter assay was employed to verify the target of miR-1299. Additionally, the proliferation, apoptosis and metastasis of AGS and SGC7901 cells were analyzed after the overexpression of miR-1299. RESULTS: Our study showed the expression of miR-1299 was decreased in GC tissues and cell lines. It indicated that the cell proliferation, migration and invasion was inhibited, while the cell apoptosis was promoted by the over-expressed miR-1299. Also, we found that miR-1299 could directly target the 3'-untranslated region (3'UTR) of ARF6 genes. In addition, rescue assay demonstrated that miR-1299 overexpression promoted the cell apoptosis and inhibited cell growth, which could be attenuated by the overexpression of ARF6. CONCLUSIONS: These findings indicate that miR-1299 regulates cell progression in GC by targeting ARF6 genes, and suggest that miR-1299 may be a tumor suppressor in the GC progression.

3D deep learning versus the current methods for predicting tumor invasiveness of lung adenocarcinoma based on high-resolution computed tomography images.

Background: Different pathological subtypes of lung adenocarcinoma lead to different treatment decisions and prognoses, and it is clinically important to distinguish invasive lung adenocarcinoma from preinvasive adenocarcinoma (adenocarcinoma in situ and minimally invasive adenocarcinoma). This study aims to investigate the performance of the deep learning approach based on high-resolution computed tomography (HRCT) images in the classification of tumor invasiveness and compare it with the performances of currently available approaches. Methods: In this study, we used a deep learning approach based on 3D conventional networks to automatically predict the invasiveness of pulmonary nodules. A total of 901 early-stage non-small cell lung cancer patients who underwent surgical treatment at Shanghai Chest Hospital between November 2015 and March 2017 were retrospectively included and randomly assigned to a training set (n=814) or testing set 1 (n=87). We subsequently included 116 patients who underwent surgical treatment and intraoperative frozen section between April 2019 and January 2020 to form testing set 2. We compared the performance of our deep learning approach in predicting tumor invasiveness with that of intraoperative frozen section analysis and human experts (radiologists and surgeons). Results: The deep learning approach yielded an area under the receiver operating characteristic curve (AUC) of 0.946 for distinguishing preinvasive adenocarcinoma from invasive lung adenocarcinoma in the testing set 1, which is significantly higher than the AUCs of human experts (P<0.05). In testing set 2, the deep learning approach distinguished invasive adenocarcinoma from preinvasive adenocarcinoma with an AUC of 0.862, which is higher than that of frozen section analysis (0.755, P=0.043), senior thoracic surgeons (0.720, P=0.006), radiologists (0.766, P>0.05) and junior thoracic surgeons (0.768, P>0.05). Conclusions: We developed a deep learning model that achieved comparable performance to intraoperative frozen section analysis in determining tumor invasiveness. The proposed method may contribute to clinical decisions related to the extent of surgical resection.

Protective effect of glycyrrhizin on coronary microembolization-induced myocardial dysfunction in rats.

Coronary microembolization (CME)-induced inflammation and cardiomyocyte apoptosis are two key factors contributing to CME-induced myocardial dysfunction. High-mobility group box-1 (HMGB1) plays essential role in progression of CME-induced injury and inhibition of HMGB1 has been shown to be protective. In present study, the potential effects of glycyrrhizin, a HMGB1 inhibitor, on CME-induced myocardial dysfunction are evaluated. Using a rat model of CME, we administrated glycyrrhizin in rats prior to CME induction. The level of HMGB1, TNF-α, iNOS, IL-6, IL-1ß, cleaved caspase-3, Bax, and Bcl-2 were measured. The serum level of cardiac troponin I, creatine kinase, was detected. The cardiac function and cardiomyocyte apoptosis were evaluated. The activation of TLR4/NF-κB signaling pathway was analyzed. Glycyrrhizin prevented CME-induced production of HMGB1, TNF-α, iNOS, IL-6, and IL-1ß. Glycyrrhizin inhibited CME-induced cardiomyocyte apoptosis and the expression of cleaved caspase-3 and Bax, while enhanced the expression of Bcl-2. Glycyrrhizin decreased cardiac troponin I and creatine kinase levels and improved cardiac function. Glycyrrhizin prevented the activation of HMGB1/TLR4/NF-κB signaling pathway. Glycyrrhizin ameliorated myocardial dysfunction in CME rats by preventing inflammation and apoptosis of cardiomyocytes.

Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma.

BACKGROUND: CD8+ T cells work as a key effector of adaptive immunity and are closely associated with immune response for killing tumor cells. It is crucial to understand the role of tumor-infiltrating CD8+ T cells in uveal melanoma (UM) to predict the prognosis and response to immunotherapy. MATERIALS AND METHODS: Single-cell transcriptomes of UM with immune-related genes were combined to screen the CD8+ T-cell-associated immune-related genes (CDIRGs) for subsequent analysis. Next, a prognostic gene signature referred to tumor-infiltrating CD8+ T cells was constructed and validated in several UM bulk RNA sequencing datasets. The risk score of UM patients was calculated and classified into high- or low-risk subgroup. The prognostic value of risk score was estimated by using multivariate Cox analysis and Kaplan-Meier survival analysis. Moreover, the potential ability of gene signature for predicting immunotherapy response was further explored. RESULTS: In total, 202 CDIRGs were screened out from the single-cell RNA sequencing of GSE139829. Next, a gene signature containing three CDIRGs (IFNGR1, ANXA6, and TANK) was identified, which was considered as an independent prognostic indicator to robustly predict overall survival (OS) and metastasis-free survival (MFS) of UM. In addition, the UM patients were classified into high- and low-risk subgroups with different clinical characteristics, distinct CD8+ T-cell immune infiltration, and immunotherapy response. Gene set enrichment analysis (GSEA) showed that immune pathways such as allograft rejection, inflammatory response, interferon alpha and gamma response, and antigen processing and presentation were all positively activated in low-risk phenotype. CONCLUSION: Our work gives an inspiration to explain the limited response for the current immune checkpoint inhibitors to UM. Besides, we constructed a novel gene signature to predict prognosis and immunotherapy responses, which may be regarded as a promising therapeutic target.

Evaluating the eighth edition TNM staging system for esophageal cancer among patients receiving neoadjuvant therapy: A SEER study.

BACKGROUND: The evaluation of the eighth edition of ypTNM staging system for patients with esophageal cancer was limited in the setting of neoadjuvant therapy. METHODS: A total of 2324 patients with esophageal cancer receiving radio(chemo)therapy prior to surgery from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2013 were eligible for the analysis. Kaplan-Meier method and Cox proportional hazards models were used to estimate overall survivals. RESULTS: Among patients with preoperative therapy, both the seventh edition TNM grouping and the eighth edition ypTNM grouping could significantly stratify the overall survival (both log-rank P < .001). There was not significant difference in the C-index of the seventh edition TNM grouping (0.575; 95%CI, 0.558-0.593) and the eighth edition ypTNM grouping (0.569; 95%CI, 0.551-0.587) (P = .098). In multivariable Cox analysis, ypN category was the strongest predictor of overall survival (P < .001), followed by tumor grade (HR, 1.33; 95%CI, 1.12-1.56; P = .001). The combination of ypT, ypN, and ypG categories yielded significantly higher C-index (0.591; 95%CI, 0.573-0.609) than that of the seventh edition TNM staging (P = .024). CONCLUSION: Tumor grade remained an independent predictor of overall survival in the setting of neoadjuvant therapy, and could improve the performance of ypTNM staging system.

Circulating miR-130 and its target PPAR-γ may be potential biomarkers in patients of coronary artery disease with type 2 diabetes mellitus.

BACKGROUND: Patients of coronary artery disease (CAD) with type 2 diabetes mellitus (DM2) show increased mortality risk than CAD patients without DM2, while few biomarkers can be used to discriminate them. METHODS: Fifty-nine patients of CAD with DM2 (DM2-CAD group), 79 patients of CAD without DM2 (CAD group), and 63 healthy control subjects were recruited. Circulating miR-130 (miR-130a and miR-130b) and PPAR-γ (peroxisome proliferator-activated receptor gamma) were measured and their Pearson correlation was analyzed. 3' UTR binding prediction and luciferase assay were used to determine the target relationship between miR-130 and PPAR-γ. Receiver operating characteristics (ROC) analysis was performed to test the discrimination ability of miR-130 between DM2-CAD and CAD groups. RESULTS: miR-130a and miR-130b showed decreased expression in DM2-CAD group when compared with the CAD group and health control. Both bioinformatics and luciferase assays showed that miR-130 could bind the 3' UTR of PPAR-γ. Furthermore, miR-130 negatively correlated with PPAR-γ in both CAD and DM2-CAD group in Pearson's coefficient analysis. Both miR-130a and miR-130b were able to discriminate DM2-CAD group from CAD group and control subjects. CONCLUSION: Circulating miR-130 may regulate the expression of PPAR-γ and can be used as a biomarker to discriminate DM2-CAD from CAD.

Presence of micropapillary and solid patterns are associated with nodal upstaging and unfavorable prognosis among patient with cT1N0M0 lung adenocarcinoma: a large-scale analysis.

PURPOSE: To investigate whether the presence of micropapillary and solid patterns are associated with nodal upstaging and survival patterns in patients with cT1N0M0 lung adenocarcinoma. METHOD: We retrospectively analyzed the clinicopathologic data of 2571 patients undergoing lobectomy and lymph node dissection or sampling. Logistic and Cox regression analysis were applied to determine the association between histological patterns and nodal upstaging and survival. RESULTS: Nodal upstaging was detected in 115 patients (4.5%) through postoperative pathologic examination. Tumors absent of lepidic pattern, and present with acinar, micropapillary and solid patterns had significantly higher nodal upstaging rate (all P < 0.001). Presence of micropapillary [odds ratios (ORs) = 3.51; 95% confidence intervals (CI) = 2.09-5.89; P < 0.001] and solid (OR 2.28; 95% CI 1.42-3.64; P = 0.001) patterns were independent predictors for nodal upstaging. Presence of micropapillary and solid patterns also significantly deteriorated the recurrence-free survival (RFS) (both log-rank P < 0.001), and were independently associated with unfavorable RFS in multivariable Cox analysis RFS [micropapillary: hazard ratios (HR) = 1.41; 95% CI 1.04-1.99; P = 0.041; solid: HR 2.05; 95% CI 1.56-2.70; P < 0.001]. CONCLUSION: The analysis of a large-scale cohort demonstrated that the presence of micropapillary and solid patterns significantly increase the risk of nodal upstaging and are independently associated with unfavorable prognosis.

A study of electric field distribution in Benjamin type proportional counter using finite element method.

Tissue equivalent proportional counters (TEPCs)  are commonly based on the Benjamin type of concept. Initially the electric field is optimized by pulse height measurement methods and only one optimum solution was established at that time. In this paper, the electric field distribution is analyzed and optimized using a three-dimensional finite element method. The calculations show that the characteristics of the radial electric field distribution of this type of counters can be equated to cylindrical counters using a pair of appropriate field shaping electrode. Furthermore, the paper analyzes the axial electric field distribution and the possibility of achieving a uniform electric field along its anode while reducing the size of Benjamin type proportional counter design down to 1/10 of currently feasible values with respect to the thinnest available anode wire diameters.

Disease-free survival improved by use of adjuvant EGFR tyrosine kinase inhibitors in resectable non-small cell lung cancer: an updated meta-analysis.

BACKGROUND: A previous meta-analysis of our research team suggested survival advantage from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after surgery in patients with EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to follow up on the findings of the previous one and presents our latest updates through the past few years. METHODS: The study advanced the previous meta-analysis and included a comprehensive range of relevant studies in PubMed. Disease-free survival (DFS) with hazard ratios (HRs) was calculated using random and/or fixed-effects models. Subgroup analysis and meta-regression analysis were also performed. RESULTS: A total of 2,223 patients in seven studies were eligible for the analysis. Adjuvant EGFR-TKIs administration was significantly associated with superior DFS [HR, 0.60; 95% confidence interval (CI), 0.42-0.87], corresponding to an absolute benefit of 3.4% at 3 years, yet with significant heterogeneity (I2=80.0%, P <0.001). EGFR mutation rate of included patients was found to be a source of heterogeneity by meta-regression analysis (P=0.005). In the EGFR-mutant sub-population, HR for DFS was 0.51 (95% CI, 0.39-0.65), corresponding to an absolute benefit of 7.1% at 3 years. The rate of overall grade 3 or greater adverse events (AEs) was 38.9% (95% CI, 35.9-41.9%). CONCLUSIONS: The updated meta-analysis provided strengthened evidence of significant DFS advantage of adjuvant EGFR-TKI treatment for patients with EGFR-mutant NSCLC after complete resection.

Palmatine attenuates isoproterenol-induced pathological hypertrophy via selectively inhibiting HDAC2 in rats.

This study aimed to exploit the potential therapeutic value of palmatine in treatment of cardiac hypertrophy and the underlying molecular mechanism. Rat hypertrophy model was established by intraperitoneal isoproterenol (ISO) injection. The hypertrophy was evaluated with cardiac hypertrophic parameters, hemodynamic parameters, lipid profile, and non-specific cardiac markers. The animals were intraperitoneally administrated with either palmatine or vehicle. The relative expressions of ANP, BNP, HDAC2, HDAC5, KLF4, and INPP5F transcripts were determined by real-time polymerase chain reaction (PCR). The relative protein levels of HDAC2, HDAC5, KLF4, and INPP5F were analyzed by immunoblotting. Palmatine treatment significantly attenuated ISO-induced hypertrophy in rats and elicited remarkable repressions in ANP, BNP, and HDAC2 transcriptions but not HDAC5. The downstream effector genes KLF4 and INPP5F were greatly restored in a dose-dependent manner in response to palmatine treatment. Our data demonstrated that palmatine possessed promising therapeutic potential against hypertrophy, which was mediated by modulation of HDAC2-KLF4/INPP5F pathway.

Outcomes of adjuvant epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutant non-small-cell lung cancer: a propensity-score analysis.

Small molecule tyrosine kinase inhibitors (TKIs) have transformed the management of advanced non-small-cell lung cancer (NSCLC) harboring activating epithelial growth factor receptor (EGFR) mutations, while the efficacy of TKIs in the adjuvant setting remains unclear. We collected the data of 209 EGFR-mutant NSCLC patients receiving complete resection from 2010 to 2013. Study end points were disease-free survival (DFS) and overall survival (OS). Among the eligible patients, 41 (19.6%) received EGFR TKIs in the adjuvant treatment. The 3-year DFS of adjuvant EGFR TKIs treatment group (70.5%, 95% CI, 54.6-86.4%) was significantly superior that control group (50.2%, 95% CI, 40-60.4%; log-rank P = 0.014). TKIs treatment (HR, 0.51; 95% CI, 0.29-0.97; P = 0.04) was significantly associated with improved DFS in multivariate Cox analysis. No significant difference was observed in 3-year OS between two groups (73.1% [58.0-88.2%] vs 61.8% [52.2-71.4%], log-rank P = 0.21). Propensity-score matching further confirmed that adjuvant TKIs treatment extended the DFS (log-rank P = 0.024), but did not improve OS (log-rank P = 0.40). Our analysis revealed that adjuvant EGFR TKIs treatment was beneficial for early-stage NSCLC patients harboring activating EGFR mutations after complete resection.