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There is no consensus about whether relatively large mediastinal tumors (≥ 5.0 cm) are suitable for video-assisted thoracoscopic surgery (VATS). Therefore, this study aimed to compare the efficacy and safety of intercostal approach VATS for large-sized anterior mediastinal tumors (5.0-10.0 cm) with no invasion to the surrounding tissues and organs. A total of 129 patients with anterior mediastinal tumors who received surgery in our hospital between January 2018 and July 2022 were consecutively enrolled. Patients were divided into 2 groups based on mediastinal tumor diameter: Group A (tumor size between 1.0 and 4.9 cm) and Group B (tumor size between 5.0 and 10.0 cm). The primary endpoints were operation time, blood loss, and postoperative pain, and the secondary endpoints were the volume of drainage, drainage duration, postoperative hospital stay, and postoperative complications. Significant differences were found in the volume of drainage between the two groups (Group A: 218.4 ± 140.6, Group B: 398.9 ± 369.3, P < 0.001). However, no differences were found in operation time, blood loss, drainage duration, postoperative hospital stay and duration of postoperative oral analgesics (P > 0.05). In addition, there existed no significant differences in the postoperative complications. Intercostal approach VATS is regarded as a feasible and safe surgical method for large-sized anterior mediastinal tumors (5.0-10.0 cm) with no invasion to the surrounding tissues and organs.
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Tiempo de Internación , Neoplasias del Mediastino , Cirugía Torácica Asistida por Video , Humanos , Cirugía Torácica Asistida por Video/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Mediastino/cirugía , Neoplasias del Mediastino/patología , Adulto , Tempo Operativo , Complicaciones Posoperatorias , Resultado del Tratamiento , Dolor Postoperatorio/etiología , Anciano , Drenaje/métodos , Estudios Retrospectivos , Estudios de Factibilidad , Pérdida de Sangre QuirúrgicaRESUMEN
OBJECTIVES: To clarify if the mechanism of Sanliangsan in improving Sjogren's syndrome complicated with interstitial lung disease (SS-ILD) involves MUC1 suppression, which is involved in SS-ILD pathogenesis. METHODS: Fifty-six patients were randomly divided into two groups receiving Sanliangsan prescription (SP) therapy and conventional therapy (western medicine). In-depth transcriptome profiles from a large database of SS-ILD patients were collected and analyzed to identify candidate genes involved in SS pathogenesis. Clinical symptom scores, metabolic compositions, lung HRCT (high-resolution computed tomography) scores, and serum MUC1 levels were compared between the two groups before and after treatment. Network pharmacology, molecular docking, and ITC assays were performed to identify bioactive compounds of SP in improving SS. Metabolome analyzed the metabolic composition of serum associated with SS-ILD before and after SP treatment. RESULTS: Transcriptome results identified the involvement of abnormal expression of genes relevant to the immune system, inflammatory responses, and signaling pathways. Numerous genes, including CD58, CD86, CTLA4, CXCL8, STAT1, and especially MUC1, were involved in SS pathogenesis and could be used to diagnose SS-ILD early. Both treatments improved the lung HRCT scores and clinical symptoms of SS-ILD. The SP therapy improved SS-ILD more effectively than conventional therapy. Moreover, Sanliangsan prescription therapy reduced serum MUC1 levels and restored the abnormal metabolisms, improving the abnormal inflammatory and immune responses of patients. Eugenol directly interacted with MUC1, suppressed related genes, and was the bioactive compound of SP. SP could partially restore the abnormal metabolisms associated with SS-ILD pathogenesis. CONCLUSION: Based on conventional Western medicine treatment, modified Sanliangsan can significantly improve the clinical symptoms, signs, and lung function of patients; the mechanism may be due to eugenol and related to MUC1 regulation.
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BACKGROUND: The diagnosis and treatment of depression in patients with chronic heart failure (CHF) is challenging, with no ideal treatment at present. AIM: To analyze the clinical intervention effect of Xuefu Zhuyu decoction (XFZYD) on CHF complicated with depression. METHODS: The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023, of which 55 received Western medicine (control group) and 61 received XFZYD (research group). Data on clinical effectiveness, traditional Chinese medicine (TCM) syndrome score, cardiac function, negative emotions, and serum inflammatory factors, were collected for comparative analyses. RESULTS: Compared with the control group, the research group had an evidently higher total effective rate. Furthermore, there were marked reductions in TCM symptom score, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, Self-Rating Depression Scale, Hamilton Depression Scale, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 in the research group after treatment, and these were lower than the corresponding values in the control group. Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment. CONCLUSION: Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients' symptoms, improved cardiac function, relieved negative emotions, and reduced the levels of serum inflammatory factors.
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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.
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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.
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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.
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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.
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Anticuerpos Monoclonales Humanizados , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/cirugía , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Terapia Neoadyuvante/métodos , Cisplatino/uso terapéutico , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Fructosa , Neoplasias Pulmonares/genética , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas , Ciclooctanos , Lignanos , Neoplasias Pulmonares , Compuestos Policíclicos , Humanos , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Ciclooctanos/farmacología , Receptores ErbB/genética , Lignanos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Simulación del Acoplamiento Molecular , Compuestos Policíclicos/farmacologíaRESUMEN
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.
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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.
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Acetamidas , Purificación del Agua , Animales , Ratones , ARN Ribosómico 16S , Purificación del Agua/métodos , Nitrógeno/química , Trastornos de la MemoriaRESUMEN
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.
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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.
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Ghrelina , Insuficiencia Cardíaca , Humanos , Ghrelina/uso terapéutico , Qi , Depresión/terapia , Estudios Prospectivos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
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.
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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.
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Lesión Renal Aguda , Paro Cardíaco , Humanos , Estudios Retrospectivos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Área Bajo la Curva , Paro Cardíaco/etiología , Frecuencia CardíacaRESUMEN
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.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Animales , Ratones , Adenocarcinoma del Pulmón/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glucólisis , Histonas , Ácido Láctico , Neoplasias Pulmonares/genéticaRESUMEN
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.
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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.
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Carcinoma , Neoplasias Esofágicas , Humanos , Adenosina , Neoplasias Esofágicas/genética , Inmunoterapia , ARN MensajeroRESUMEN
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.