E2F1 Facilitates the Proliferation and Stemness of Gastric Cancer Cells by Activating CDC25B Transcription and Modulating the MAPK Pathway.

Gastric cancer (GC) is a health problem that concerns people around the world. CDC25B is an essential cell cycle regulatory factor that is overexpressed in a variety of tumor cells. CDC25B plays a vital part in the progression and proliferation of malignant tumors. However, it is not yet clear that how CDC25B affects the stemness of GC cells. The study used bioinformatics to detect the expression of E2F1 and CDC25B in GC tissues and their correlation, as well as pathways enriched by CDC25B. We detected the expression of E2F1 and CDC25B in GC cell lines using quantitative reverse transcription polymerase chain reaction and tested the combination relationship between E2F1 and CDC25B using chromatin immunoprecipitation (ChIP) and dual-luciferase assays. We measured cell viability using CCK-8 assay, evaluated sphere-forming efficiency using sphere formation assay, and determined cell proliferation ability using colony formation assay. We also analyzed the expression of stemness markers and MAPK pathway-related proteins using western blot. In GC tissues and cells, CDC25B was upregulated. Silencing CDC25B could affect the MAPK pathway, thereby repressing the proliferation and stemness of GC cells. As predicted by bioinformatics, CDC25B had an upstream transcription factor, E2F1, which also had a high expression level in GC. Dual-luciferase and ChIP assays confirmed the combination relationship between the two. Rescue experiments uncovered that overexpression of CDC25B could reverse the impact induced by E2F1 knockdown on proliferation and stemness of cells. In conclusion, E2F1 could activate CDC25B transcription to regulate the MAPK pathway and enhance the proliferation and stemness of GC cells. We revealed a potential regulatory pathway of stemness of GC cells that was mediated by CDC25B, providing new ideas for improving and innovating GC treatment.

Altered thalamus functional connectivity in patients with acute unilateral vestibulopathy: a resting-state fMRI study.

Objective: Acute unilateral vestibulopathy (AUVP) is the second leading cause of peripheral vestibular vertigo. Full recovery of AUVP is related to sufficient central vestibular compensation. It has been confirmed that the vestibular nucleus and vestibular cortex are involved in the process of vestibular compensatory in AUVP patients. However, few studies have focused on the functional compensation of thalamus in patients with AUVP. This study aimed to explore the alterations of resting-state functional connectivity (FC) focused on thalamus using functional magnetic resonance imaging (fMRI) in AUVP patients. Methods: Data of 3D-T1 and resting-state fMRI were collected from 40 AUVP patients and 35 healthy controls (HC). Seeds-based (bilateral thalamus) FC was analyzed to investigate the changes in FC between the two groups. Furthermore, we evaluated the associations between altered thalamus FC and clinical features in AUVP patients using Pearson's partial correlation. Results: Compared with HC, AUVP patients showed decreased FC between bilateral thalamus and left insula. We also observed decreased FC between right thalamus and left supramarginal gyrus. Additionally, we found increased FC between left thalamus and right postcentral gyrus (PCG), as well as increased FC between right thalamus and regions of bilateral PCG, right middle frontal gyrus and right middle occipital gyrus in AUVP patients. Furthermore, the FC between left thalamus and left insula was negatively correlated with values of canal paresis in patients with AUVP (p = 0.010, r = -0.434). Conclusion: Our results provided first evidence for the decreased thalamo-vestibular cortex pathway, as well as increased thalamo-somatosensory and thalamo-visual cortex pathway in AUVP patients. These findings help us better understand the underlying mechanisms of central dynamic compensatory following an acute unilateral peripheral vestibular damage.

Evaluations of secondary hypertension and laboratory data in the elderly population.

Secondary hypertension in the elderly poses many challenges and requires a comprehensive diagnostic and management approach. This review explores the prevalence, diagnostic strategies, and treatment modalities for secondary hypertension in elderly patients, focusing on etiologies including primary aldosteronism, renal vascular disease, renal parenchymal disease, obstructive sleep apnea, thyroid disorders, Cushing's syndrome, pheochromocytomas and paragangliomas, and drug-induced hypertension. Key considerations include age-related changes in physiology and atypical presentations of underlying conditions necessitating thorough screening with a combination of clinical evaluation, laboratory tests, and imaging studies. Collaboration among healthcare providers is essential to ensure a timely diagnosis and personalized management tailored to the unique needs of elderly patients. Further research is needed to address knowledge gaps and optimize clinical strategies for managing secondary hypertension in this population.

OGA mutant aberrantly hydrolyzes O-GlcNAc modification from PDLIM7 to modulate p53 and cytoskeleton in promoting cancer cell malignancy.

O-GlcNAcase (OGA) is the only human enzyme that catalyzes the hydrolysis (deglycosylation) of O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation) from numerous protein substrates. OGA has broad implications in many challenging diseases including cancer. However, its role in cell malignancy remains mostly unclear. Here, we report that a cancer-derived point mutation on the OGA's noncatalytic stalk domain aberrantly modulates OGA interactome and substrate deglycosylation toward a specific set of proteins. Interestingly, our quantitative proteomic studies uncovered that the OGA stalk domain mutant preferentially deglycosylated protein substrates with +2 proline in the sequence relative to the O-GlcNAcylation site. One of the most dysregulated substrates is PDZ and LIM domain protein 7 (PDLIM7), which is associated with the tumor suppressor p53. We found that the aberrantly deglycosylated PDLIM7 suppressed p53 gene expression and accelerated p53 protein degradation by promoting the complex formation with E3 ubiquitin ligase MDM2. Moreover, deglycosylated PDLIM7 significantly up-regulated the actin-rich membrane protrusions on the cell surface, augmenting the cancer cell motility and aggressiveness. These findings revealed an important but previously unappreciated role of OGA's stalk domain in protein substrate recognition and functional modulation during malignant cell progression.

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study.

BACKGROUND: Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods. METHODS: We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored. RESULTS: Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05). CONCLUSIONS: Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

Using optical coherence tomography to assess luster of pearls: technique suitability and insights.

Luster is one of the vital indexes in pearl grading. To find a fast, nondestructive, and low-cost grading method, optical coherence tomography (OCT) is introduced to predict the luster grade through the texture features. After background removal, flattening, and segmentation, the speckle pattern of the region of interest is described by seven kinds of feature textures, including center-symmetric auto-correlation (CSAC), fractal dimension (FD), Gabor, gray level co-occurrence matrix (GLCM), histogram of oriented gradients (HOG), laws texture energy (LAWS), and local binary patterns (LBP). To find the relations between speckle-derived texture features and luster grades, four Four groups of pearl samples were used in the experiment to detect texture differences based on support vector machines (SVMs) and random forest classifier (RFC)) for investigating the relations between speckle-derived texture features and luster grades. The precision, recall, F1-score, and accuracy are more significant than 0.9 in several simulations, even after dimension reduction. This demonstrates that the texture feature from OCT images can be applied to class the pearl luster based on speckle changes.

Anticoagulation for Patients With Concomitant Atrial Fibrillation and End-Stage Renal Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population. METHODS AND RESULTS: An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation. CONCLUSIONS: For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.

Fractional Amplitude of Low-Frequency Fluctuation and Voxel-Mirrored Homotopic Connectivity in Patients with Persistent Postural-Perceptual Dizziness: Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: Persistent postural-perception dizziness (PPPD) is a chronic subjective form of dizziness characterized by the exacerbation of dizziness with active or passive movement, complex visual stimuli, and upright posture. Therefore, we aimed to analyze the resting-state functional magnetic resonance imaging (fMRI) in patients with PPPD using fractional amplitude of low-frequency fluctuation (fALFF) and voxel-mirrored homotopic connectivity (VMHC) and evaluate the correlation between abnormal regions in the brain and clinical features to investigate the pathogenesis of PPPD. Methods: Thirty patients with PPPD (19 females and 11 males) and 30 healthy controls (HCs; 18 females and 12 males) were closely matched for age and sex. The fALFF and VMHC methods were used to investigate differences in fMRI (BOLD sequences) between the PPPD and HC groups and to explore the associations between areas of functional abnormality and clinical characteristics (dizziness, anxiety, depression, and duration). Result: Compared to the HC group, patients with PPPD displayed different functional change patterns, with increased fALFF in the right precuneus and decreased VMHC in the bilateral precuneus. In addition, patients with PPPD had a positive correlation between precuneus fALFF values and dizziness handicap inventory (DHI) scores, and a negative correlation between VMHC values and the disease duration. Conclusions: Precuneus dysfunction was observed in patients with PPPD. The fALFF values correlated with the degree of dizziness in PPPD, and changes in VMHC values were associated with the duration of dizziness, suggesting that fMRI changes in the precuneus of patients could be used as a potential imaging marker for PPPD.

Profiling Human Cerebrospinal Fluid (CSF) Endogenous Peptidome in Alzheimer's Disease.

Human cerebrospinal fluid (CSF) is a rich source for central nervous system (CNS)-related disease biomarker discovery due to its direct interchange with the extracellular fluid of the CNS. Though extensive proteome-level profiling has been conducted for CSF, studies targeting at its endogenous peptidome is still limited. It is more difficult to include the post-translational modifications (PTMs) characterization of the peptidome in the mass spectrometry (MS) analysis because of their low abundance and the challenge of data interpretation. In this chapter, we present a peptidomic workflow that combines molecular weight cut-off (MWCO) separation, electron-transfer and higher-energy collision dissociation (EThcD) fragmentation, and a three-step database searching strategy for comprehensive PTM analysis of endogenous peptides including both N-glycosylation and O-glycosylation and other common peptide PTMs. The method has been successfully adopted to analyze CSF samples from healthy donors, mild cognitive impairment (MCI), and Alzheimer's disease (AD) patients to provide a landscape of peptidome in different disease states.

[Effect of Preserving the Pulmonary Branch of Vagus Nerve on Postoperative Cough 
in Patients with Stage I Peripheral Lung Adenocarcinoma].

BACKGROUND: Cough is one of the main complications after pulmonary surgery, which seriously affects the postoperative quality of life. Preserving the pulmonary branch of vagus nerve may reduce the incidence of postoperative cough. Therefore, the aim of this study was to investigate whether preserving the pulmonary branch of the vagus nerve could reduce the incidence of postoperative chronic cough in patients with stage I peripheral lung adenocarcinoma. METHODS: A total of 125 patients who underwent single-port thoracoscopic radical resection for lung cancer in the Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China from June 2022 to June 2023 were retrospectively selected, and divided into two groups according to whether the vagopulmonary branch was preserved during the operation, namely, the vagopulmonary branch group (n=61) and the traditional group (n=64). The general clinical data, perioperative conditions, lymph node dissection, Mandarin Chinese version of The Leicester Cough Questionnaire (LCQ-MC) scores before and 8 weeks after operation were recorded in the two groups. Both the two groups were divided into tamponade group and non-tamponade group according to whether autologous fat or gelatin sponge was tamponade after lymph node dissection. LCQ-MC scores and postoperative chronic cough of both groups were calculated. RESULTS: The LCQ-MC score of the traditional group was significantly lower than that of the vagopulmonary branch group in physiological, psychological, social and total scores at 8 weeks after surgery, and the difference was statistically significant (P<0.05). There were more cough patients in the traditional group than the vagopulmonary branch group at 8 weeks after surgery, with significant difference (P=0.006). Subgroup analysis was conducted separately for the vagopulmonary branch group and the traditional group. Among the patients in the vagopulmonary branch group and the traditional group, the LCQ-MC scores of the non-tamponade group 8 weeks after surgery were lower than those of the tamponade group (P<0.05). There were more patients with cough in the group 8 weeks after surgery than in the tamponade group (P=0.001, P=0.024). CONCLUSIONS: For patients with stage I peripheral lung adenocarcinoma, the preservation of the pulmonary branch of vagus nerve is safe and effective, which can reduce the incidence of postoperative chronic cough and improve the postoperative quality of life of the patients.

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

Increased functional connectivity between default mode network and visual network potentially correlates with duration of residual dizziness in patients with benign paroxysmal positional vertigo.

Objective: To assess changes in static and dynamic functional network connectivity (sFNC and dFNC) and explore their correlations with clinical features in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning maneuvers (CRM) using resting-state fMRI. Methods: We studied resting-state fMRI data from 39 BPPV patients with RD compared to 38 BPPV patients without RD after successful CRM. Independent component analysis and methods of sliding window and k-means clustering were adopted to investigate the changes in dFNC and sFNC between the two groups. Additionally, temporal features and meta-states were compared between the two groups. Furthermore, the associations between fMRI results and clinical characteristics were analyzed using Pearson's partial correlation analysis. Results: Compared with BPPV patients without RD, patients with RD had longer duration of BPPV and higher scores of dizziness handicap inventory (DHI) before successful CRM. BPPV patients with RD displayed no obvious abnormal sFNC compared to patients without RD. In the dFNC analysis, patients with RD showed increased FNC between default mode network (DMN) and visual network (VN) in state 4, the FNC between DMN and VN was positively correlated with the duration of RD. Furthermore, we found increased mean dwell time (MDT) and fractional windows (FW) in state 1 but decreased MDT and FW in state 3 in BPPV patients with RD. The FW of state 1 was positively correlated with DHI score before CRM, the MDT and FW of state 3 were negatively correlated with the duration of BPPV before CRM in patients with RD. Additionally, compared with patients without RD, patients with RD showed decreased number of states and state span. Conclusion: The occurrence of RD might be associated with increased FNC between DMN and VN, and the increased FNC between DMN and VN might potentially correlate with the duration of RD symptoms. In addition, we found BPPV patients with RD showed altered global meta-states and temporal features. These findings are helpful for us to better understand the underlying neural mechanisms of RD and potentially contribute to intervention development for BPPV patients with RD.

Altered parietal operculum cortex 2 functional connectivity in benign paroxysmal positional vertigo patients with residual dizziness: A resting-state fMRI study.

AIMS: To investigate changes in functional connectivity (FC) focusing on parietal operculum cortex 2 (OP2) in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning procedure (CRP). METHODS: High-resolution three-dimensional T1 and resting-state functional magnetic resonance imaging (fMRI) were performed on 55 healthy controls (HCs), 55 BPPV patients with RD, and 55 patients without RD after successful CRP. Seed-based (bilateral OP2) FC was calculated to investigate the changes in FC among the three groups. Additionally, we further explored the associations between abnormal FC and clinical symptoms. RESULTS: One-way analysis of covariance showed significant FC differences among the three groups. Post-hoc analysis showed that patients with RD exhibited decreased FC between left OP2 and regions of left angular gyrus (AG), thalamus, precuneus, middle frontal gyrus (MFG), and right cerebellum posterior lobe (CPL) in comparison with HCs. In addition, compared with patients without RD, patients with RD showed decreased FC between left OP2 and regions of left MFG, AG, middle temporal gyrus, and right CPL. Moreover, in patients with RD, the FC between left thalamus and OP2 was negatively correlated with duration of RD, and the FC between left AG and OP2 was negatively correlated with duration of BPPV. CONCLUSION: BPPV patients with RD showed reduced FC between brain regions involved in vestibular processing and spatial cognition; These results suggested that BPPV patients with RD might have diminished central processing of vestibular information and impaired spatial cognition.

Network Pharmacology and In vitro Experimental Verification to Explore the Mechanism of Chaiqin Qingning Capsule in the Treatment of Pain.

BACKGROUND: Chaiqin Qingning capsule (CQQNC) has been used to relieve pain in practice. However, the active components, pain targets, and molecular mechanisms for pain control are unclear. OBJECTIVE: To explore the active components and potential mechanisms of the analgesic effect of CQQNC through network pharmacology and in vitro experiments. METHODS: The main active components and the corresponding targets of CQQNC were screened from the TCMSP and the SwissTargetPrediction databases. Pain-related targets were selected in the OMIM, Gene- Cards, and DrugBank databases. These targets were intersected to obtain potential analgesic targets. The analgesic targets were imported into the STRING and DAVID databases for protein-protein interaction (PPI), gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Cytoscape software (V3.7.1) was used to construct an active component-intersection network. Finally, the key components were docked with the core targets. The analgesic mechanism of CQQNC was verified by RAW264.7 cell experiment. RESULTS: 30 active CQQNC components, 617 corresponding targets, and 3,214 pain-related target genes were found. The main active components were quercetin, kaempferol, and chenodeoxycholic acid etc. The key targets were ALB, AKT1, TNF, IL6, TP53, IL1B, and SRC. CQQNC can exert an analgesic effect through PI3K-Akt, MAPK signaling pathways, etc. Molecular docking showed that these active components had good binding activities with key targets. The results of in vitro experiments showed that CQQNC could exert antiinflammatory and analgesic effects through MAPK/AKT/NF-kB signaling pathways. CONCLUSION: CQQNC exerts pain control through inhibiting MAPK/AKT/NF-kB signaling pathways.

Helicobacter pylori CagA protein induces gastric cancer stem cell-like properties through the Akt/FOXO3a axis.

The presence of Helicobacter pylori (H. pylori) infection poses a substantial risk for the development of gastric adenocarcinoma. The primary mechanism through which H. pylori exerts its bacterial virulence is the cytotoxin CagA. This cytotoxin has the potential to induce inter-epithelial mesenchymal transition, proliferation, metastasis, and the acquisition of stem cell-like properties in gastric cancer (GC) cells infected with CagA-positive H. pylori. Cancer stem cells (CSCs) represent a distinct population of cells capable of self-renewal and generating heterogeneous tumor cells. Despite evidence showing that CagA can induce CSCs-like characteristics in GC cells, the precise mechanism through which CagA triggers the development of GC stem cells (GCSCs) remains uncertain. This study reveals that CagA-positive GC cells infected with H. pylori exhibit CSCs-like properties, such as heightened expression of CD44, a specific surface marker for CSCs, and increased ability to form tumor spheroids. Furthermore, we have observed that H. pylori activates the PI3K/Akt signaling pathway in a CagA-dependent manner, and our findings suggest that this activation is associated with the CSCs-like characteristics induced by H. pylori. The cytotoxin CagA, which is released during H. pylori infection, triggers the activation of the PI3K/Akt signaling pathway in a CagA-dependent manner. Additionally, CagA inhibits the transcription of FOXO3a and relocates it from the nucleus to the cytoplasm by activating the PI3K/Akt pathway. Furthermore, the regulatory function of the Akt/FOXO3a axis in the transformation of GC cells into a stemness state was successfully demonstrated.

[Establishment of a Predictive Model for Chronic Cough after Pulmonary Resection].

BACKGROUND: Chronic cough after pulmonary resection is one of the most common complications, which seriously affects the quality of life of patients after surgery. Therefore, the aim of this study is to explore the risk factors of chronic cough after pulmonary resection and construct a prediction model. METHODS: The clinical data and postoperative cough of 499 patients who underwent pneumonectomy or pulmonary resection in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to June 2023 were retrospectively analyzed. The patients were randomly divided into training set (n=348) and validation set (n=151) according to the principle of 7:3 randomization. According to whether the patients in the training set had chronic cough after surgery, they were divided into cough group and non-cough group. The Mandarin Chinese version of Leicester cough questionnare (LCQ-MC) was used to assess the severity of cough and its impact on patients' quality of life before and after surgery. The visual analog scale (VAS) and the self-designed numerical rating scale (NRS) were used to evaluate the postoperative chronic cough. Univariate and multivariate Logistic regression analysis were used to analyze the independent risk factors and construct a model. Receiver operator characteristic (ROC) curve was used to evaluate the discrimination of the model, and calibration curve was used to evaluate the consistency of the model. The clinical application value of the model was evaluated by decision curve analysis (DCA). RESULTS: Multivariate Logistic analysis screened out that preoperative forced expiratory volume in the first second/forced vital capacity (FEV1/FVC), surgical procedure, upper mediastinal lymph node dissection, subcarinal lymph node dissection, and postoperative closed thoracic drainage time were independent risk factors for postoperative chronic cough. Based on the results of multivariate analysis, a Nomogram prediction model was constructed. The area under the ROC curve was 0.954 (95%CI: 0.930-0.978), and the cut-off value corresponding to the maximum Youden index was 0.171, with a sensitivity of 94.7% and a specificity of 86.6%. With a Bootstrap sample of 1000 times, the predicted risk of chronic cough after pulmonary resection by the calibration curve was highly consistent with the actual risk. DCA showed that when the preprobability of the prediction model probability was between 0.1 and 0.9, patients showed a positive net benefit. CONCLUSIONS: Chronic cough after pulmonary resection seriously affects the quality of life of patients. The visual presentation form of the Nomogram is helpful to accurately predict chronic cough after pulmonary resection and provide support for clinical decision-making.

Transcription factor E2F3 activates CDC25B to regulate DNA damage and promote mitoxantrone resistance in stomach adenocarcinoma.

BACKGROUND: CDC25B, as a member of the cell cycle regulating protein family, is located in the cytoplasm and is involved in the transition of the cell cycle and mitosis. CDC25B is highly expressed in various tumors and is a newly discovered oncogene. This study aimed to investigate the impact of CDC25B on mitoxantrone resistance in stomach adenocarcinoma (STAD) and its possible mechanisms. METHODS: This study analyzed the expression of CDC25B and its potential transcription factor E2F3 in STAD, as well as the IC50 values of tumor tissues by bioinformatics analysis. Expression levels of CDC25B and E2F3 in STAD cells were measured by qRT-PCR. MTT was utilized to evaluate cell viability and IC50 values of STAD cells, and comet assay was utilized to analyze the level of DNA damage in STAD cells. Western blot was used to analyze the expression of DNA damage-related proteins. The targeting relationship between E2F3 and CDC25B was validated by dual-luciferase and ChIP assays. RESULTS: Bioinformatics analysis and molecular experiments showed that CDC25B and E2F3 were highly expressed in STAD, and CDC25B was enriched in the mismatch repair and nucleotide excision repair pathways. The IC50 values of tumor tissues with high expression of CDC25B were relatively high. Dual-luciferase and ChIP assays confirmed that CDC25B could be transcriptionally activated by E2F3. Cell experiments revealed that CDC25B promoted mitoxantrone resistance in STAD cells by regulating DNA damage. Further research found that low expression of E2F3 inhibited mitoxantrone resistance in STAD cells by DNA damage, but overexpression of CDC25B reversed the impact of E2F3 knockdown on mitoxantrone resistance in STAD cells. CONCLUSION: This study confirmed a novel mechanism by which E2F3/CDC25B mediated DNA damage to promote mitoxantrone resistance in STAD cells, providing a new therapeutic target for STAD treatment.

Development of a dynamic gas lock inhibited model for EUV-induced carbon deposition.

The optical surface of extreme ultraviolet (EUV) lithography machines is highly vulnerable to contamination by hydrocarbons, resulting in the formation of carbon deposits that significantly degrade the quality and efficiency of lithography. The dynamic gas lock (DGL) has been proven as an effective approach to alleviate carbon deposition. However, the majority of existing studies on carbon deposition neglect the influence of the DGL. This paper is dedicated to investigating the phenomena of hydrocarbon adsorption, desorption, and cleavage with considering the effects of the DGL. A comprehensive mathematical model of the carbon deposition process is established, and the impact of radiation intensity, temperature, and hydrocarbon types on the depositing rate is considered. The results suggest that the primary cause of carbon deposition is the direct cracking of hydrocarbons induced by photons with a wavelength range between 12.5 and 14.5 nm. Additionally, it has been observed that the carbon deposition rate decreases exponentially as clean gas flow increases when EUV radiation intensity exceeds 50 mW/mm2. Conversely, at low EUV radiation intensity, clean gas flow has little effect on the carbon deposition rate. An effective approach to mitigate carbon deposition is to elevate the temperature of the optical surface and employ light hydrocarbon materials in the EUV process.

Post-exercise left atrial conduit strain predicted hemodynamic change in heart failure with preserved ejection fraction.

OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: • Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. • Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. • Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.