A survival nomogram model for patients with resectable non-small cell lung cancer and lymph node metastasis (N1 or N2) based on the Surveillance, Epidemiology, and End Results Database and single-center data.

Background: The ability to predict survival in patients with lymph node metastasis has long been elusive. After surgery, the basis for decision-making on the combination treatment of patients is not clear. The purpose of this study was thus to build a survival nomogram model to effectively predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and lymph node metastasis. The number of dissected lymph nodes (NDLN), number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were included in this study to determine the risk factors in patients with advanced NSCLC. Methods: The data of 5,132 patients with NSCLC and lymph node metastasis (N1 or N2) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database according to inclusion and exclusion criteria and used as the training cohort. We enrolled 117 patients from the First Affiliated Hospital, Zhejiang University School of Medicine as the external validation cohort. Receiver operating characteristic (ROC) analyses were performed to determine the best cutoff values for predicting the prognosis of patients with NSCLC. Based on the risk factors affecting prognosis, a nomogram was constructed using univariate and multivariate Cox proportional hazard regression models. The discrimination ability of the nomogram was evaluated with the concordance index (C-index) and calibration curves. For the independent risk factors, survival curves were drawn using Kaplan-Meier analysis. Results: ROC curve analysis showed that the optimal NPLN cut-off value was 4, LNR was 0.26, and LODDS was -0.25, respectively. However, LNR was nonsignificant in multivariate analysis, with a P value of 0.274. The novel survival nomogram model included seven independent risk factors, among which were NPLN, LODDS, and chemotherapy. Model 4, which included N stage, NPLN, and LODDS, had a higher likelihood ratio (LR) and C-index than did the other models. The C-index was 0.648 [95% confidence interval (CI): 0.636-0.659] in the training cohort and 0.807 (95% CI: 0.751-0.863) in the external validation cohort, showing good prognostic accuracy and discrimination ability. According to the median risk score, the patients in the training cohort and external validation cohort were divided into high-risk and low-risk groups, between which significant differences in OS were found. In the training cohort, age, sex, T stage, N stage, NPLN, LODDS, and chemotherapy were significantly associated with OS (P<0.001). In the external validation cohort, T stage, NPLN, LODDS, and chemotherapy were found to be correlated with OS. Conclusions: The NPLN and LODDS nomogram is an accurate survival prediction tool for patients with N1 or N2 NSCLC. Patients with lymph node metastasis can benefit from chemotherapy, but no evidence shows that radiotherapy is necessary for patients with resectable NSCLC.

Comparisons of short-term outcomes between robot-assisted, video-assisted, and open esophagectomy for resectable esophageal cancer after neoadjuvant treatment: a retrospective study.

Background: Robot-assisted esophagectomy (RAE), video-assisted minimally invasive esophagectomy (VAMIE), and open esophagectomy (OE) all have significant roles in the management of esophageal cancer (EC). Few studies have compared efficacy and safety between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Therefore, this study aimed to explore the short-term outcomes between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Methods: Ninety-eight patients were consecutively enrolled who underwent esophagectomy. A retrospective study was performed including 98 consecutive patients treated from January 2021 to August 2022 who received neoadjuvant treatment (including immunochemotherapy and chemoradiotherapy) followed by RAE, VAMIE or OE. Evaluated endpoints in the present study consisted of pathological outcomes, intraoperative and postoperative outcomes, as well as postoperative complications. Results: No significant differences were seen in the operating time, blood loss, length of intensive care unit (ICU) stay, R0 resection, and number of dissected lymph nodes between the three RAE, VAMIE, or OE groups. The achievement rate of right recurrent laryngeal nerve (RLN) lymph node removal (P=0.01) and the total cost (P<0.001) were higher in RAE. The postoperative hospital stay of OE was longer than the other two groups (P<0.05). There were no significant differences in postoperative complications. Conclusions: Compared to VAMIE, no clear benefit exists for RAE in the treatment of resectable EC after neoadjuvant therapy. OE resulted in a longer hospital stay. Although the rate of successful right RLN node removal was higher with RAE, the clinical relevance for this is yet unclear.

Does the time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery affect outcomes for locally advanced esophageal squamous cell carcinoma?

BACKGROUND: There is currently no consensus on the optimal interval time between neoadjuvant therapy and surgery, and whether prolonged time interval from neoadjuvant therapy to surgery results in bad outcomes for locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we aim to evaluate outcomes of time intervals ≤ 8 weeks and > 8 weeks in locally advanced ESCC. METHODS: This retrospective study consecutively included ESCC patients who received esophagectomy after neoadjuvant camrelizumab combined with chemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. The primary endpoints were disease-free survival (DFS) and overall survival (OS), while the secondary endpoints were pathological response, surgical outcomes, and postoperative complications. RESULTS: From 2019 to 2021, a total of 80 patients were included in our study and were divided into two groups according to the time interval from neoadjuvant immunochemotherapy to surgery: ≤ 8 weeks group (n = 44) and > 8 weeks group (n = 36). The rate of MPR in the ≤ 8 weeks group was 25.0% and 27.8% in the > 8 weeks group (P = 0.779). The rate of pCR in the ≤ 8 weeks group was 11.4%, with 16.7% in the > 8 weeks group (P = 0.493). The incidence of postoperative complications in the ≤ 8 weeks group was 27.3% and 19.4% in the > 8 weeks group (P = 0.413). The median DFS in the two groups had not yet reached (hazard ratio [HR], 3.153; 95% confidence interval [CI] 1.383 to 6.851; P = 0.004). The median OS of ≤ 8 weeks group was not achieved (HR, 3.703; 95% CI 1.584 to 8.657; P = 0.0012), with the > 8 weeks group 31.6 months (95% CI 21.1 to 42.1). In multivariable analysis, inferior DFS and OS were observed in patients with interval time > 8 weeks (HR, 2.992; 95% CI 1.306 to 6.851; and HR, 3.478; 95% CI 1.481 to 8.170, respectively). CONCLUSIONS: Locally advanced ESCC patients with time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery > 8 weeks were associated with worse long-term survival.

Optimal therapeutic strategy for non-small cell lung cancer with thoracic extrathoracic metastasis: a study based on SEER database.

Background: Non-small cell lung cancer (NSCLC) patients with extrathoracic metastasis (EM) are a highly heterogeneous cohort. Some of these patients could benefit from primary tumor surgery. This study aimed to identify potential NSCLC patients with EM suitable for primary tumor resection and to determine the optimal therapeutic strategy. Methods: NSCLC patients with EM were extracted from the Surveillance, Epidemiology and End Results database between 2010 and 2015. They were stratified into subgroups with single and multi-EMs. Cox regression analysis was adopted to identify prognostic factors for overall survival (OS). The Kaplan-Meier method was used to compare the OS among patients who received different treatment modalities. Results: The univariate Cox regression analysis demonstrated that advanced age, male sex, race (black), married status, squamous cell carcinoma, higher histological grade, advanced T or N stage, contralateral lung metastasis, multi-EMs, tumor size >2 cm, and lack of treatment were associated with poorer OS in patients with NSCLC (P<0.05). Multivariate Cox regression analysis revealed that the number of EM and treatment modalities were independent prognostic factors affecting OS (P<0.001). For patients with single EM, those who did not receive treatment and those who underwent single-agent chemotherapy, single-agent surgery, surgery combined with chemotherapy, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy had median OS times of 3.0, 11.0, 12.0, 26.0, 11.0, and 25.0 months, respectively. Compared to monotherapy, combination therapy showed significant benefits for patients with single EM in NSCLC. Furthermore, patients with single EM who underwent lobectomy, bilobectomy, or pneumonectomy had significantly longer survival than those who underwent sublobar resection, even when the primary tumor size was ≤2 cm (P=0.04). Conclusions: Primary tumor surgery could benefit NSCLC patients with single EM; lobectomy was at least warranted to improve survival even for primary tumors with size ≤2 cm.

Schizandrin A induces non-small cell lung cancer apoptosis by suppressing the epidermal growth factor receptor activation.

OBJECTIVE: The purpose of this study is to explore the biological mechanism of Schizandrin A (SchA) inducing non-small cell lung cancer (NSCLC) apoptosis. METHODS: The reverse molecular docking tool "Swiss Target Prediction" was used to predict the targets of SchA. Protein-protein interaction analysis was performed on potential targets using the String database. Functional enrichment analyses of potential targets were performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The conformation of SchA binding to target was simulated by chemical-protein interactomics and molecular docking. The effect of SchA on the expression and phosphorylation level of EGFR was detected by Western blot. Lipofectamine 3000 and EGFR plasmids were used to overexpress EGFR. Apoptosis was tested with Annexin V-FITC and propidium iodide staining, and cell cycle was detected by propidium iodide staining. RESULTS: The "Swiss Target Prediction" database predicted 112 and 111 targets based on the 2D and 3D structures of SchA, respectively, of which kinases accounted for the most, accounting for 24%. Protein interaction network analyses showed that molecular targets such as ERBB family and SRC were at the center of the network. Functional enrichment analyses indicated that ERBB-related signaling pathways were enriched. Compound-protein interactomics and molecular docking revealed that SchA could bind to the ATP-active pocket of the EGFR tyrosine kinase domain. Laboratory results showed that SchA inhibited the phosphorylation of EGFR. Insulin could counteract the cytotoxic effect of SchA. EGFR overexpression and excess EGF or IGF-1 had limited impacts on the cytotoxicity of SchA. CONCLUSIONS: Network pharmacology analyses suggested that ERBB family members may be the targets of SchA. SchA can inhibit NSCLC at least in part by inhibiting EGFR phosphorylation, and activating the EGFR bypass can neutralize the cytotoxicity of SchA.

FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation.

The existence of cancer stem cells is widely acknowledged as the underlying cause for the challenging curability and high relapse rates observed in various tumor types, including non-small cell lung cancer (NSCLC). Despite extensive research on numerous therapeutic targets for NSCLC treatment, the strategies to effectively combat NSCLC stemness and achieve a definitive cure are still not well defined. The primary objective of this study was to examine the underlying mechanism through which Fructose-1,6-bisphosphatase 1 (FBP1), a gluconeogenic enzyme, functions as a tumor suppressor to regulate the stemness of NSCLC. Herein, we showed that overexpression of FBP1 led to a decrease in the proportion of CD133-positive cells, weakened tumorigenicity, and decreased expression of stemness factors. FBP1 inhibited the activation of Notch signaling, while it had no impact on the transcription level of Notch 1 intracellular domain (NICD1). Instead, FBP1 interacted with NICD1 and the E3 ubiquitin ligase FBXW7 to facilitate the degradation of NICD1 through the ubiquitin-proteasome pathway, which is independent of the metabolic enzymatic activity of FBP1. The aforementioned studies suggest that targeting the FBP1-FBXW7-NICD1 axis holds promise as a therapeutic approach for addressing the challenges of NSCLC recurrence and drug resistance.

W-Net: A boundary-aware cascade network for robust and accurate optic disc segmentation.

Accurate optic disc (OD) segmentation has a great significance for computer-aided diagnosis of different types of eye diseases. Due to differences in image acquisition equipment and acquisition methods, the resolution, size, contrast, and clarity of images from different datasets show significant differences, resulting in poor generalization performance of deep learning networks. To solve this problem, this study proposes a multi-level segmentation network. The network includes data quality enhancement module (DQEM), coarse segmentation module (CSM), localization module (OLM), and fine segmentation stage module (FSM). In FSM, W-Net is proposed for the first time, and boundary loss is introduced in the loss function, which effectively improves the performance of OD segmentation. We generalized the model in the REFUGE test dataset, GAMMA dataset, Drishti-GS1 dataset, and IDRiD dataset, respectively. The results show that our method has the best OD segmentation performance in different datasets compared with state-of-the-art networks.

2,2-Dichloroacetamide exposure induces behavior and memory disorders in mice: Detrimental effects of long-term dietary restriction on neurotoxicity.

2, 2-dichloroacetamide (DCAcAm), a nitrogen-containing disinfection byproduct (DBPs), is commonly found in potable water. This study aimed to compare the neurotoxicity of DCAcAm in C57/BL6 mice at both environmentally relevant and higher doses through oral exposure over a 28-day period. Furthermore, the potential effects of dietary restriction (DR) on the cerebral toxicity induced by 20 ppb DCAcAm were examined. The findings indicated that DCAcAm exposure and DR treatment resulted in reduced memory retention and cognitive adaptability in mice. Additionally, higher doses of DCAcAm exposure induced severe brain inflammation and oxidative stress. Metabolic profiling revealed disruptions in fatty acid, energy, and amino acid metabolism in the brain. Remarkably, the negative impacts of 20 ppb DCAcAm on the mice brain were worsened by DR treatment. Analysis of 16S rRNA sequencing revealed notable changes in the composition and structure of intestinal microorganisms after exposure to DCAcAm. This study discovered that DCAcAm has both direct effects on the brain and indirect effects through the microbial-brain-intestinal axis, which collectively result in neurotoxicity and dietary restriction exacerbates these effects. This study provides emerging views on the assessment of the toxicity of nitrogen containing DBPs.

Clinical evaluation of the impact of mediastinal tumour size on the subxiphoid approach video-assisted thoracoscopic surgery.

OBJECTIVES: The application of video-assisted thoracoscopic surgery (VATS) for relatively large mediastinal tumours (≥5.0 cm) has been a subject of debate, and few studies have investigated the subxiphoid approach VATS in different tumour size categories. The study aims to compare the efficacy of the subxiphoid approach VATS for achieving curative outcomes based on tumour size categories (<3.0, 3.0-4.9 and 5.0-10.0 cm). METHODS: A total of 165 patients with anterior mediastinal tumours who underwent surgery at our hospital between January 2018 and July 2022 were consecutively enrolled, categorized according to tumour size-group A (<3.0 cm): 58, group B (3.0-4.9 cm): 70 and group C (5.0-10.0 cm): 37. Clinical baseline data, intraoperative and postoperative outcomes, and postoperative complications were analysed. RESULTS: The study revealed significant differences in operation time among the 3 groups (group A: 103.4 ± 36.1, group B: 106.4 ± 35.2, group C: 127.4 ± 44.8; P < 0.05) as well as in the volume of drainage (group A: 273.3 ± 162.0, group B: 411.9 ± 342.6, group C: 509.7 ± 543.7; P < 0.05). However, no differences were seen in blood loss, drainage duration, postoperative hospital stay and duration of postoperative oral analgesics. Additionally, the incidence of postoperative complications did not exhibit significant differences across these groups. CONCLUSIONS: Subxiphoid approach VATS is considered a feasible and safe surgical method for large-sized anterior mediastinal tumours (5.0-10.0 cm) with no invasion to the surrounding tissues and organs.

Safety and efficacy of tislelizumab plus chemotherapy as preoperative treatment in potentially resectable locally advanced non-small-cell lung cancer patients.

OBJECTIVES: Locally advanced non-small-cell lung cancer (LA-NSCLC) requires more preoperative regiments in the era of immunotherapy. Tislelizumab was approved for first-line treatment for advanced lung cancer, bringing hope for preoperative therapy in LA-NSCLC. The aim of this study was to investigate the safety and efficacy of preoperative tislelizumab plus chemotherapy in LA-NSCLC. METHODS: The medical records at the First Affiliated Hospital of Zhejiang University were examined retrospectively from September 2019 to June 2022 for this descriptive single-arm cohort study. Patients with LA-NSCLC were treated with tislelizumab plus platinum-based dual-drug regimens for 2-6 cycles and regular imaging assessments were performed every 1-2 cycles. Data including demographic characteristics, clinicopathological staging, adverse events and surgery-related details were recorded in specifically designed forms. RESULTS: Forty patients met the inclusion criteria of the study and 23 patients underwent curative intent surgeries. Significantly clinical and pathological downstaging was observed, with the objective response rate being 65.00%, leading to a major pathological remission (MPR) rate of 56.52% and a pathological complete remission (pCR) rate of 34.78%. Grade 3-4 treatment-related adverse events occurred in 4 patients and no perioperative death occurred. The 1-year progress-free survival rate and the 1-year overall survival rate were 85.0% and 90.0%, respectively. CONCLUSIONS: Tislelizumab plus chemotherapy as preoperative therapy demonstrates promising antitumour activity for potentially resectable LA-NSCLC with high MPR, pCR and acceptable toxicity and survival.

Clinical Value of Heart Qi in the Treatment of Chronic Heart Failure With Depression.

Context: Chronic heart failure (CHF) is a form of persistent heart failure. If a patient develops depression, it can worsen the severity of heart failure and can lead to adverse outcomes. No researchers have studied the effects of tonic heart qi soup for patients with CHF and depression. Objective: The study intended to evaluate the clinical efficacy of tonic heart qi soup in the treatment of chronic heart failure (CHF) for patients with comorbid depression. Design: The research team performed a prospective randomized controlled trial. Setting: The study took place in the Department of Chinese Medicine at Cangzhou Central Hospital in Cangzhou, Hebei Province, China. Participants: Participants were 120 patients with CHF at the hospital as inpatients or outpatients between January 2016 and January 2019. Intervention: The research team divided participants into two groups, with 60 patients each: (1) an intervention group, which received conventional Western medical treatment combined with treatment with a commercial tonic heart qi soup and (2) a control group, which received conventional Western medical treatment only. Outcome Measures: The research team measured: (1) treatment efficacy, (2) cardiac function, (3) adverse reactions, (4) B-type natriuretic peptide (BNP) and Ghrelin, and (5) depression. Results: In the intervention group, 55 participants showed significant improvement in the degree of heart failure, for a total effectiveness rate of 91.67%, which was significantly higher than that of the control group (P = .000). The intervention group had 10 participants in class II, 18 in class III, and 22 in class IV. Among them, 28 participants improved, indicating significantly better outcomes than those of the control group. The intervention group's BNP levels, at 1031.58 ± 118.83 pg/ml, and ghrelin levels, at 481.46 ± 57.53%, were significantly lower than those of the control group. No liver- or renal-function damage, insomnia, or significant adverse reactions occurred for either group. The intervention group's total incidence rate for adverse reactions, at 1.67%, was significantly lower than that of the control group, at 11.67% (P = .000) and also had a higher total effective rate in reducing depression, at 86.67%, compared to that of the control group, at 43.33%. Conclusions: Heart Qi Tonic Tang, as an adjunctive therapy, significantly improved outcomes for CHF patients with depression. It effectively reduced heart failure symptoms, with minimal adverse reactions and increased patient comfort and compliance.

BZW2 Modulates Lung Adenocarcinoma Progression through Glycolysis-Mediated IDH3G Lactylation Modification.

Histone lactylation (Hla) is a metabolically stress-related histone modification that featured in specific gene expression regulation. However, the role of Hla in the pathogenesis of lung adenocarcinoma (LUAD) remains unexplored. Through bioinformatics analysis, we found that BZW2 exhibited an elevated level of expression in LUAD tissues, which was associated with a poor prognosis. Flow cytometry and TUNEL assay were used to analyze the apoptosis of LUAD cells and tissues, respectively. The effect of the cell function experiment on the LUAD cell phenotype was analyzed. An XF 96 Extracellular Flux Analyzer measured the ECAR value, and kits were used to detect lactate production and glucose consumption. Animal experiments were performed for further verification. Cell experiments showed that BZW2 fostered the malignant progression of LUAD by promoting glycolysis-mediated lactate production and lactylation of IDH3G. In a compelling in vivo validation, the inhibition of Hla could suppress the malignant progression of LUAD. Knockdown of BZW2 combined with 2-DG treatment significantly repressed tumor growth in mice. BZW2 could regulate the progression of LUAD through glycolysis-mediated IDH3G lactylation, offering a theoretical basis for the targeted treatment of LUAD with glycolysis and Hla.

Construction and validation of a risk prediction model for acute kidney injury in patients after cardiac arrest.

OBJECTIVE: Identifying patients at high risk for cardiac arrest-associated acute kidney injury (CA-AKI) helps in early preventive interventions. This study aimed to establish and validate a high-risk nomogram for CA-AKI. METHODS: In this retrospective dataset, 339 patients after cardiac arrest (CA) were enrolled and randomized into a training or testing dataset. The Student's t-test, non-parametric Mann-Whitney U test, or χ2 test was used to compare differences between the two groups. Optimal predictors of CA-AKI were determined using the Least Absolute Shrinkage and Selection Operator (LASSO). A nomogram was developed to predict the early onset of CA-AKI. The performance of the nomogram was assessed using metrics such as area under the curve (AUC), calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: In total, 150 patients (44.2%) were diagnosed with CA-AKI. Four independent risk predictors were identified and integrated into the nomogram: chronic kidney disease, albumin level, shock, and heart rate. Receiver operating characteristic (ROC) analyses showed that the nomogram had a good discrimination performance for CA-AKI in the training dataset 0.774 (95%CI, 0.715-0.833) and testing dataset 0.763 (95%CI, 0.670-0.856). The AUC values for the two groups were calculated and compared using the Hanley-McNeil test. No statistically significant differences were observed between the groups. The calibration curve demonstrated good agreement between the predicted outcome and actual observations. Good clinical usefulness was identified using DCA and CIC. CONCLUSION: An easy-to-use nomogram for predicting CA-AKI was established and validated, and the prediction efficiency of the clinical model has reasonable clinical practicability.

Experimental demonstration of deterministic quantum search for multiple marked states without adjusting the oracle.

Grover's search algorithm is a well-known quantum algorithm that has been extensively studied and improved to increase its success rate and enhance its flexibility. However, most improved search algorithms require an adjustment of the oracle, which may not be feasible in practical problem-solving scenarios. In this work, we report an experimental demonstration of a deterministic quantum search for multiple marked states without adjusting the oracle. A linear optical setup is designed to search for two marked states, one in a 16-state database with an initial equal-superposition state and the other in an 8-state database with different initial nonequal-superposition states. The evolution of the probability of finding each state in the database is also measured and displayed. Our experimental results agree well with the theoretical predictions, thereby proving the feasibility of the search protocol and the implementation scheme. This work is a pioneering experimental demonstration of deterministic quantum search for multiple marked states without adjusting the oracle.

The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma.

Esophageal carcinoma (EC) is always diagnosed at advanced stage and its the mortality rate remains high. The patients usually miss the best opportunity for treatment because of non-specific symptoms and the survival rates are low. N6-methyladenosine (m6A) the predominant modification in eukaryotic messenger RNA(mRNA), serves vital roles in numerous bioprocess. This chemical modification is dynamic, reversible and consists of three regulators: m6A methyltransferases (writers), demethylases (erasers) and m6A-binding proteins (readers). Recently, a growing number of evidences have indicated relationships between m6A and EC. Whereas, lacking of cognition about the molecular mechanism of m6A modification in esophageal carcinoma. We will focus on the biological function roles of m6A modification in the tumorigenesis and development of EC. Recent studies showed that immunotherapy had a positive impact on EC. The relationship between m6A and immunotherapy in EC deserves further research and discussion. We will also discuss the potential clinical applications regarding diagnosis, treatment and prognosis of m6A modification for EC and provide perspectives for further studies.

Underestimated health risks: Dietary restriction magnify the intestinal barrier dysfunction and liver injury in mice induced by polystyrene microplastics.

Microplastics (MPs) have gained significant attention due to their widespread presence in the environment. While studies have been conducted to investigate the risks associated with MPs, the potential effects of MPs on populations with varying dietary habits, such as dietary restriction (DR), remain largely undefined. The sensitivity of the body to invasive contaminants may increase due to insufficient food intake. Here, we aimed to investigate whether dietary restriction could affect the toxicity of MPs in mice. Following a 5-week exposure to 200 µg/L polystyrene microplastics (PSMPs), DR-PSMPs treatment group exhibited significant intestinal barrier dysfunction compared to ND-PSMPs treatment group, as determined by histopathological and biochemical analysis. Dietary restriction worsened liver oxidative stress and bile acid disorder in mice exposed to PSMPs. 16S rRNA sequencing analysis revealed that DR-PSMPs treatment caused alterations in gut microbiota composition, including the downregulation of probiotics abundance and upregulation of pathogenic bacteria abundance. The negative effects caused by PSMPs in mice with dietary restriction could attribute to increased MPs bioaccumulation, declined water intake, reduced probiotics abundance, and elevated pathogenic bacteria abundance, as well as the susceptibility of the dietary restriction individual. Our findings hint that the biological effects of contaminants could be affected by dietary habits.

Non­diagnostic electromagnetic navigation bronchoscopy biopsy: Predictive factors and final diagnoses.

The present study aimed to explore the final diagnosis of pulmonary nodules with an initial non-diagnostic result on electromagnetic navigation bronchoscopy (ENB) biopsy and the predictive factors for a non-diagnostic result. A total of 198 nodules from 194 patients that were suspected to be malignant tumors were included in the present study. The initial biopsy pathology results were divided into two groups: The diagnostic group and the non-diagnostic group. The diagnostic group was defined as a successful initial biopsy to obtain a diagnosis, including malignant and benign diagnoses. The non-diagnostic group was defined as a non-specific benign diagnosis, normal lung tissue or an unsuccessful biopsy. Among the 198 nodules, 139 (70.2%) were in the diagnostic group and 59 (29.8%) were in the non-diagnostic group. Predictive factors for a non-diagnostic biopsy included nodule size ≤1.5 cm [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.03-4.09], non-solid nodules (OR, 2.71; 95% CI, 1.33-5.64) and nodules in the left lung (OR, 2.50; 95% CI, 1.27-4.92). Of the 59 non-diagnostic biopsies, 46 were finally confirmed to be malignant by surgery. Notably, non-diagnostic biopsies with non-solid nodules (OR, 7.64; 95% CI, 3.11-18.76) were more likely to be malignant. In conclusion, the predictive factors for a non-diagnostic biopsy were nodule size ≤1.5 cm and non-solid nodules. It was not rare for patients to finally be diagnosed with a malignancy in the non-diagnostic group. Therefore, care should be taken when the results of an ENB are non-diagnostic to prevent misdiagnosis.

Down-regulation of FBP1 in lung adenocarcinoma cells promotes proliferation and invasion through SLUG mediated epithelial mesenchymal transformation.

Background: Metabolic reprogramming and epithelial-mesenchymal transformation (EMT) play an important role in lung cancer. In recent studies, metabolic enzymes such as Fructose-1,6-bisphosphatase 1 (FBP1) have shown potential functions beyond regulating metabolism. Methods: Western blot assay was performed to detect glycolysis-related and EMT-related protein expression levels. The glucose uptake kit and adenosine triphosphate (ATP) detection kit were used to detect glucose uptake rate and ATP content. Transwell assay was used to determine the invasiveness of lung adenocarcinoma cells. Wound healing assay was used to determine the metastatic ability of lung adenocarcinoma cells. Methyl thiazolyl tetrazolium (MTT) assay and EdU staining were performed to investigate the effect of FBP1 overexpression on lung adenocarcinoma proliferation. Results: Overexpression of FBP1 down-regulated glycolysis-related protein levels and inhibited glucose uptake and ATP production, while knockdown of FBP1 had the opposite effect. Overexpression of FBP1 reversed EMT and inhibited Slug expression. Meanwhile, overexpression of FBP1 impaired the invasion, metastasis and proliferation ability of lung adenocarcinoma cells. In contrast, FBP1 knockdown promoted the EMT process, up-regulated Slug expression and enhanced the invasion, metastasis and proliferation of lung adenocarcinoma cells. Conclusions: Therefore, FBP1 can be used as one of the potential clinical targets through inhibiting glycolysis, cell invasion and proliferation by inhibiting Slug mediated EMT processes.

Baicalein attenuates bleomycin-induced lung fibroblast senescence and lung fibrosis through restoration of Sirt3 expression.

CONTEXT: Fibroblast senescence was reported to contribute to the pathological development of idiopathic pulmonary fibrosis (IPF), and baicalein is reported to attenuate IPF. OBJECTIVE: This study explores whether baicalein attenuates lung fibrosis by regulating lung fibroblast senescence. MATERIALS AND METHODS: Institute of Cancer Research (ICR) mice were randomly assigned to control, bleomycin (BLM), baicalein and BLM + baicalein groups. Lung fibrosis was established by a single intratracheal dose of BLM (3 mg/kg). The baicalein group received baicalein orally (100 mg/kg/day). Sirtuin 3 (Sirt3) siRNA (50 µg) was injected through the tail vein once a week for 2 weeks to explore its effect on the anti-pulmonary fibrosis of baicalein. RESULTS: BLM-treated mice exhibited obvious lung fibrosis and fibroblast senescence by showing increased levels of collagen deposition (27.29% vs. 4.14%), hydroxyproline (208.05 vs. 40.16 ng/mg), collagen I (25.18 vs. 9.15 µg/mg), p53, p21, p16, MCP-1, PAI-1, TNF-α, MMP-10 and MMP-12 in lung tissues, which were attenuated by baicalein. Baicalein also mitigated BLM-mediated activation of TGF-ß1/Smad signalling pathway. Baicalein restored the BLM-induced downregulation of Sirt3 expression in lung tissues and silencing of Sirt3 abolished the inhibitory role of baicalein against BLM-induced lung fibrosis, fibroblast senescence and activation of TGF-ß1/Smad signalling pathway. CONCLUSIONS: Baicalein preserved the BLM-induced downregulation of lung Sirt3 expression, and thus the suppression of TGF-ß1/Smad signalling pathway and lung fibrosis, which might provide an experimental basis for treatment of IPF.