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.

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.

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.

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.

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.

A comparative study in healthy and diabetic mice followed the exposure of polystyrene microplastics: Differential lipid metabolism and inflammation reaction.

Human exposure to microplastics (MPs) continues to occur due to ingestion of contaminated food, water and air. Intake of MPs can pose potential health risks by interfering with the production and circulation of nutrients, leading to physiological stress (such as immune responses and metabolic abnormalities). Toxicity data of MPs based on healthy individuals may not be applicable to large populations of patients with chronic diseases represented by diabetes. Therefore, in this study, the response of diabetic mice was compared with that of healthy mice after exposure to polystyrene microplastics (PS-MPs), and interesting differences were observed. PS-MPs exposure significantly increased liver tissue damage, abnormal lipid metabolism, inflammatory effect, liver metabolic disorder and changes of intestinal microbial composition in diabetic mice. Moreover, PS-MPs overstated abnormal lipid metabolism in diabetic mice. The difference between the increased inflammation after exposure to PS-MPs in healthy and diabetic mice involves that the former is mainly modulated by gut microbes, while diabetic mice seem to be more susceptible to lipid metabolism disturbances. In addition, the size effect of MPs was also observed in diabetic mice. These results suggested that individuals with chronic diseases may be more sensitive to pollution due to altered homeostasis, and therefore disease status should be fully considered when assessing the health risk of pollutants.

Gensenoside Rg1 protects against lipopolysaccharide- and d-galactose-induced acute liver failure via suppressing HMGB1-mediated TLR4-NF-κB pathway.

AIM: Acute liver failure (ALF) is a life-threatening acute liver injury (ALI) with high mortality. Gensenoside Rg1 (G-Rg1) effects on Lipopolysaccharide- (LPS-) and d-galactose-(D-gal-) induced ALI, but its effects on ALF remained unclear. This paper aimed to validate its possible efficacy on ALF prevention. METHODS: For in vivo studies, histological examination was performed using hematoxylin-eosin (H&E) staining, and alanine aminotransferase (ALT), aspartate aminotransminase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) contents were measured. Levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) were quantified via enzyme-linked immunosorbent assay (ELISA). Human bronchial epithelial cell line BEAS-2B was used for ALF model in vitro and its viability was measured by MTT assay. Expressions of high mobility group box 1 (HMGB1) and toll-like receptor 4-Nuclear Factor-κB (TLR4-NF-κB) pathway-related proteins were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. RESULTS: G-Rg1 relieved LPS- and D-gal-induced hepatic injury, and reduced ALT, AST and MDA levels but upregulated SOD and GSH levels, with downregulation on TNF-α and IL-6 levels. Expressions of HMGB1, TLR4 and NF-κB pathway-related proteins were also down-regulated after G-Rg1 treatment both in vivo and in vitro, while BEAS-2B cell viability was increased. However, overexpressed HMGB1 reversed the effects of G-Rg1 treatment in vitro. CONCLUSION: G-Rg1 had a protective effect against LPS- and D-gal-induced ALF both in vitro and in vivo, which might be related to inhibited HMGB1-mediated TLR4-NF-κB Pathway. These discoveries suggested that G-Rg1 could be a potential agent for prevention against ALF.

The diagnostic value of a seven-autoantibody panel and a nomogram with a scoring table for predicting the risk of non-small-cell lung cancer.

The early detection of non-small-cell lung cancer (NSCLC) remains a common concern. The aim of our study was to validate the diagnostic value of a seven-autoantibody (7-AAB) panel compared with radiological diagnosis for NSCLC. We constructed a nomogram and a scoring table based on the 7-AAB panel's result to predict the risk of NSCLC. We prospectively enrolled 268 patients who presented with radiological lesions and underwent both the 7-AAB panel test and pathological diagnosis by surgical resection. A comparison between the 7-AAB panel and radiological diagnosis was performed. A nomogram and a scoring table based on the 7-AAB panel's result to predict the risk of NSCLC were constructed and internally validated. The 7-AAB panel test had a specificity of 90.2% and a positive predictive value (PPV) of 92.7%, which were significantly higher than those of the radiological diagnosis. The 7-AAB panel also showed a preferable sensitivity in patients with early-stage disease. Seven factors, including the 7-AAB panel results, were integrated into the nomogram. For more convenient application, we formulated a scoring table based on the nomogram. The area under the receiver operating characteristic curve was 0.840 and 0.860 in the training group and validation group, respectively, which was higher than that using the 7-AAB panel or radiological diagnosis alone. This study reveals that our 7-AAB panel has clinical value in the diagnosis of NSCLC. The utility of our nomogram and the scoring table indicated that they have the potential to assist clinicians in avoiding unnecessary treatment or needless follow-up.

A competing risk nomogram predicting cause-specific mortality in patients with lung adenosquamous carcinoma.

BACKGROUND: Adenosquamous carcinoma (ASC) is an uncommon histological subtype of lung cancer. The purpose of this study was to assess the cumulative incidences of lung cancer-specific mortality (LC-SM) and other cause-specific mortality (OCSM) in lung ASC patients, and construct a corresponding competing risk nomogram for LC-SM. METHODS: Data on 2705 patients with first primary lung ASC histologically diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) was utilized to calculate the 3-year and 5-year probabilities of LC-SM and OCSM, and a competing risk model was built. Based on the model, we developed a competing risk nomogram to predict the 3-year and 5-year cumulative probabilities of LC-SM and the corresponding concordance indexes (C-indexes) and calibration curves were derived to assess the model performance. To evaluate the clinical usefulness of the nomogram, decision curve analysis (DCA) was conducted. Furthermore, patients were categorized into three groups according to the tertile values of the nomogram-based scores, and their survival differences were assessed using CIF curves. RESULTS: The 3-year and 5-year cumulative mortalities were 49.6 and 55.8% for LC-SM and 8.2 and 11.8% for OCSM, respectively. In multivariate analysis, increasing age, male sex, no surgery, and advanced T, N and M stages were related to a significantly higher likelihood of LC-SM. The nomogram showed good calibration, and the 3-year and 5-year C-indexes for predicting the probabilities of LC-SM in the validation cohort were both 0.79, which were almost equal to those of the ten-fold cross validation. DCA demonstrated that using the nomogram gained more benefit when the threshold probabilities were set within the ranges of 0.24-0.89 and 0.25-0.91 for 3-year and 5-year LCSM, respectively. In both the training and validation cohorts, the high-risk group had the highest probabilities of LC-SM, followed by the medium-risk and low-risk groups (both P < 0.0001). CONCLUSIONS: The competing risk nomogram displayed excellent discrimination and calibration for predicting LC-SM. With the aid of this individualized predictive tool, clinicians can more expediently devise appropriate treatment protocols and follow-up schedules.

Early Protection by Resveratrol in Rat Lung Transplantation.

BACKGROUND Resveratrol is a multifunctional bioactive substance that has effects in anti-inflammation and prevention of ischemia-reperfusion injury. This study compared the inflammation and expression of related proteins during the early stages after transplantation to explore the effects and mechanisms of resveratrol on transplanted lung. MATERIAL AND METHODS Sprague-Dawley rats were randomized to receive pretreatment of resveratrol suspension (60 mg/kg; RES group), dexamethasone (1 mg/kg; DEM group), or normal saline solution (2 mL/kg; control group) 1 h before lung transplantation. The cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) of the recipients was determined 24 h after transplantation. Histopathologic evaluation, including lung injury score, and the expression of necroptosis-associated proteins was assessed. RESULTS Histopathologic evaluation showed pneumocyte damage and endothelialitis associated with hemorrhage in the alveoli in the control group, the severity of which was greater than that in the other 2 groups. The levels of interleukin-6 and tumor necrosis factor-a in the serum and BALF of the RES and DEM groups were lower than those in the control group. The expression of necroptosis-associated proteins in the RES group was lower than that in the control group, and was inversely proportional to lung injury. CONCLUSIONS Pretreatment with resveratrol protected rat lung in the early stages after transplantation. We determined a relationship between necroptosis-associated proteins and transplanted lung injury, which suggests that the mechanism of lung transplantation-associated ischemia-reperfusion injury may be related to necroptosis.

Clinical, cellular, and bioinformatic analyses reveal involvement of WRAP53 overexpression in carcinogenesis of lung adenocarcinoma.

Lung cancer, of which non-small cell lung cancer accounts for 80%, remains a leading cause of cancer-related mortality and morbidity worldwide. Our study revealed that the expression of WD repeat containing antisense to P53 (WRAP53) is higher in lung-adenocarcinoma specimens than in specimens from adjacent non-tumor tissues. The prevalence of WRAP53 overexpression was significantly higher in patients with tumor larger than 3.0 cm than in patients with tumor smaller than 3.0 cm. The depletion of WRAP53 inhibits the proliferation of lung-adenocarcinoma A549 and SPC-A-1 cells via G1/S cell-cycle arrest. Several proteins interacting with WRAP53 were identified through co-immunoprecipitation and liquid chromatography/mass spectrometry. These key proteins indicated previously undiscovered functions of WRAP53. These observations strongly suggested that WRAP53 should be considered a promising target in the prevention or treatment of lung adenocarcinoma.

Downregulation of RUVBL1 inhibits proliferation of lung adenocarcinoma cells by G1/S phase cell cycle arrest via multiple mechanisms.

Lung cancer remains a leading cause of cancer-related mortality and morbidity worldwide, of which non-small cell lung cancer (NSCLC) accounts for 80 %. RUVBL1 is a highly conserved eukaryotic AAA+ adenosine 5'-triphosphatase (ATPase) that has many functions highly relevant to cancer. We therefore attempted to determine the potential role of RUVBL1 in the biogenesis of lung adenocarcinoma and obtained some interesting results. Our study revealed that RUVBL1 expression was higher in lung adenocarcinoma specimens than in those of adjacent non-tumor tissues and in lung cancer cell lines than in normal lung cell lines. RUVBL1 knockdown via siRNA reduced proliferation and caused G1/S phase cell cycle arrest in lung adenocarcinoma cell lines. The G1/S phase cell cycle arrest triggered by RUVBL1 downregulation could be attributed, at least in part, to repression of the AKT/GSK-3ß/cyclin D1 pathway and probably to the activation of IRE1α-mediated endoplasmic reticulum (ER) stress. We thus demonstrated for the first time that a knockdown of RUVBL1 could effectively inhibit the proliferation of lung adenocarcinoma A549 and H292 cells through the induction of G1/S phase cell cycle arrest via multiple mechanisms. These observations strongly suggested that RUVBL1 should be considered a promising target for the prevention or therapy of lung adenocarcinoma.

Pressurized CEC coupled with QTOF-MS for urinary metabolomics.

Pressurized CEC (pCEC) coupled with ESI-QTOF-MS using a sheathless interface was applied for metabolomics to develop an alternative analytical method for metabolic profiling of complex biofluid samples such as urine. The hyphenated system was investigated with mixed standards and pooled urine samples to evaluate its precision, repeatability, linearity, sensitivity, and selectivity. The applied voltage, mobile phase, and gradient elution were optimized and applied for the analysis of urinary metabolites. Multivariate data analysis was subsequently performed and used to distinguish lung cancer patients from healthy controls successfully. High separation efficiency has been achieved in pCEC due to the EOF. For metabolite identification, the pCEC-MS separation mechnism was helpful for discriminating the fragment ions of glutamine conjugates from co-eluted metabolites. Three glutamine conjugates, including phenylacetylglutamine, acylglutamine C8:1, and acylglutamine C6:1 were identified among 16 differential urinary metabolites of lung cancer. Receiver-operating-characteristic analysis of acylglutamine C8:1 resulted in an area-under-curve value of 0.882. Overall, this work suggests that this pCEC-ESI-QTOF-MS method may provide a novel and useful platform for metabolomic studies due to its superior separation and identification.

Urinary metabolomic study of non-small cell lung carcinoma based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Metabolic profiles from human urine reveal the significant difference of carnitine and acylcarnitines levels between non-small cell lung carcinoma patients and healthy controls. Urine samples from cancer patients and healthy individuals were assayed in this metabolomic study using ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The data were normalized by the sum of all intensities and creatinine calibration, respectively, before orthogonal partial least squares discriminant analysis. Twenty differential metabolites were identified based on standard compounds or tandem mass spectrometry fragments. Among them, some medium-/long-chain acylcarnitines, for example, cis-3,4-methylene heptanoylcarnitine, were found to be downregulated while carnitine was upregulated in urine samples from the cancer group compared to the control group. Receiver operating characteristic analysis of the two groups showed that the area under curve for the combination of carnitine and 11 selected acylcarnitines was 0.958. This study suggests that the developed carnitine and acylcarnitines profiling method has the potential to be used for screening non-small cell lung carcinoma.

[Effects of placental growth factor on revascularization after acute myocardial infarction in rats].

OBJECTIVE: To investigate the effect of placental growth factor (PlGF) on revascularization after acute myocardial infarction. METHODS: Myocardial infarction model was established by ligation of left anterior descending coronary artery in Wistar rats. Thirty AMI rats were divided into 3 groups with 10 in each group: PlGF, mouse VEGFR-1/Flt-1 antibody, or saline (control group) was injected in the infarcted border zone for each group, respectively. Two weeks later the hemodynamics parameters were measured with a left ventricular needle catheter and a biological signal analysis system; left ventricular remodeling was observed by HE staining; angiogenesis was examined by immunohistochemistry and cardiomyocyte apoptosis rate was detected by TUNEL. RESULTS: The stroke volume, systolic pressure and left ventricular developed pressure in PlGF group were all higher than those in control group (112±7 vs 65.63±8.50 µl, P<0.01; 131.61±9.26 vs 94.84±8.53 mm Hg, P<0.01 and 175.85±11.36 vs 105.50±15.83 mm Hg, P<0.01; respectively). PlGF animals had less ventricular dilation (left ventricular diameter 8.20±0.14 vs 9.25±0.32 mm, P<0.01) and increased left ventricular wall thickness (1.81±0.10 vs 1.35±0.10 mm, P<0.01) compared to controls. The geometry parameter of anti-VEGFR1 and control animals was almost the same. PlGF animals had increased angiogenesis compared to controls (29.44±5.75 vs 15.88±2.42 endothelial cells/high-powered field, P<0.01); the alpha smooth muscle actin (α-SMA) showed that PlGF animal had a higher density of artery than others (25.14±1.83 vs 19.70±2.52 arteries/mm(2), P<0.01), and the density of artery in anti-VEFGR1 group was less than the controls. The apoptosis rate of cardiomyocytes in PlGF animals was significantly lower than that in controls (9.51%±2.75% vs 37.81%±8.74%, P<0.01). CONCLUSION: Regional delivery of PlGF following acute myocardial infarction can improve cardiac function and left ventricular remodeling, enhance angiogenesis and reduce cardiomyocyte apoptosis rate. PlGF may be a potential agent in adjuvant therapy for acute myocardial infarction.

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.

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.

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.