Roles of reactive oxygen species in inflammation and cancer.

Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS-mediated mechanisms for advancing cancer therapy and developing personalized treatments.

Assessing the impact of tear direction in coronary artery dissection on thrombosis development: A hemodynamic computational study.

OBJECTIVE: Iatrogenic coronary artery dissection is a complication of coronary intimal injury and dissection due to improper catheter manipulation. The impact of tear direction on the prognosis of coronary artery dissection (CAD) remains unclear. This study examines the hemodynamic effects of different tear directions (transverse and longitudinal) of CAD and evaluates the risk of thrombosis, rupture and further dilatation of CAD. METHODS: Two types of CAD models (Type I: transverse tear, Type II: longitudinal tear) were reconstructed from the aorto-coronary CTA dataset of 8 healthy cases. Four WSS-based indicators were analyzed, including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and cross flow index (CFI). A thrombus growth model was also introduced to predict the trend of thrombus growth in CAD with two different tear directions. RESULTS: For most of the WSS-based indicators, including TAWSS, RRT, and CFI, no statistically significant differences were observed across the CAD models with varying tear directions, except for OSI, where a significant difference was noted (p < 0.05). Meanwhile, in terms of thrombus growth, the thrombus growing at the tear of the Type I (transverse tear) CAD model extended into the true lumen earlier than that of the Type II (longitudinal tear) model. CONCLUSIONS: Numerical simulations suggest that: (1) The CAD with transverse tear have a high risk of further tearing of the dissection at the distal end of the tear. (2) The CAD with longitudinal tear create a hemodynamic environment characterized by low TAWSS and high OSI in the false lumen, which may additionally increase the risk of vessel wall injury. (3) The CAD with transverse tear may have a higher risk of thrombosis and coronary obstruction and myocardial ischemia in the early phase of the dissection.

Raman time-delay in attosecond transient absorption of strong-field created krypton vacancy.

Strong field ionization injects a transient vacancy in the atom which is entangled to the outgoing photoelectron. When the electron is finally detached, the ion is populated at different excited states with part of coherence information lost. The preserved coherence of matter after interacting with intense short pulses has important consequences on the subsequent nonequilibrium evolution and energy relaxation. Here we employ attosecond transient absorption spectroscopy to measure the time-delay of resonant transitions of krypton vacancy during their creation. We have observed that the absorptions by the two spin-orbit split states are modulated at different paces when varying the time-delay between the near-infrared pumping pulse and the attosecond probing pulse. It is shown that the coupling of the ions with the remaining field leads to a suppression of ionic coherence. Comparison between theory and experiments uncovers that coherent Raman coupling induces time-delay between the resonant absorptions, which provides insight into laser-ion interactions enriching attosecond chronoscopy.

Development and validation of a major adverse limb events prediction model for peripheral arterial disease with frailty.

OBJECTIVE: To investigate the risk factors for major limb adverse events (MALE) in peripheral arterial disease (PAD) combined with frailty and to develop and validate a risk prediction model of MALE. METHODS: This prospective study was performed in the vascular surgery department of patients in six hospitals in southwest China. Prospective collection of patients with PAD combined with frailty from February 1 to December 20, 2021, with MALE as the primary outcome, and followed for 1 year. The cohort was divided into a development cohort and a validation cohort. In the development cohort, a multivariate risk prediction model was developed to predict MALE using random forests for variable selection and multivariable Cox regression analysis. The model is represented by a visualized nomogram and a web-based calculator. The model performance was tested with the validation cohort and assessed using the C-statistic and calibration plots. RESULTS: A total of 1179 patients were prospectively enrolled from February 1 to December 20, 2021. Among 816 patients with PAD who were included in the analysis, the median follow-up period for this study was 9 ± 4.07 months, the mean age was 74.64 ± 9.43 years, and 249 (30.5%) were women. Within 1 year, 222 patients (27.2%) developed MALE. Target lesion revascularizations were performed in 99 patients (12.1%), and amputations were performed in 131 patients (16.1%). The mortality rate within the whole cohort was 108 patients (13.2%). After controlling for competing risk events (death), the cumulative risk of developing MALE was not statistically different. Prealbumin (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.41-0.89; P = .010), percutaneous coronary intervention (HR, 2.31; 95% CI, 1.26-4.21; P = .006), Rutherford classification (HR, 1.77; 95% CI, 1.36-2.31; P < .001), white blood cell (HR, 1.85; 95% CI, 1.20-2.87; P = .005), high altitude area (HR, 3.1; 95% CI, 1.43-6.75; P = .004), endovascular treatment (HR, 10.2; 95% CI, 1.44-72.50; P = .020), and length of stay (HR, 1.01; 95% CI, 1.00-1.03; P = .012) were risk factors for MALE. The MALE prediction model had a C-statistic of 0.76 (95% CI, 0.70-0.79). The C-statistic was 0.68 for internal validation and 0.66 for external validation for the MALE prediction model. The MALE prediction model for PAD presented an interactive nomogram and a web-based network calculator. CONCLUSIONS: In this study, the MALE prediction model has a discriminative ability to predict MALE among patients with PAD in frailty. The MALE model can optimize clinical decision-making for patients with PAD in frailty.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Dickkopf-1 drives perineural invasion via PI3K-AKT signaling pathway in head and neck squamous cancer.

Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf-1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1-overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K-AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1-overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease-free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K-AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer.

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011-2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Application of lipid apheresis in acute lipogenic pancreatitis.

INTRODUCTION: Recently, the incidence of hypertriglyceridemia-associated pancreatitis(HTG-AP) has been increasing. The pathogenesis of lipogenic pancreatitis is not fully understood.This study aimed to retrospectively analyze the laboratory data, clinical manifestations, and prognosis of patients with lipid-derived pancreatitis who received lipid purification,to explore whether lipid purification is a better treatment for acute hyperlipidemic pancreatitis . METHODS: In this study, we enrolled five subjects diagnosed with HTG-AP at the Second Xiangya Hospital of Central South University between 2021 and 2022. We collected demographic data, medical histories, clinical manifestations, and laboratory data. All patients received routine therapy. Blood lipid purification was conducted using the double filtration plasmapheresis (DFPP) method. Plasma was separated from blood cells and purified to remove cholesterol, triglycerides, and low-density lipoprotein (LDL). SPSS was used for statistical analyses. RESULTS: Following a single lipoprotein apheresis (LA) treatment, significant improvements in serum lipid levels were observed. Three patients achieved triglyceride levels below 5.65mmol/L within 24 hours, while the remaining two patients experienced reductions of 82% and 78%, respectively. The average triglyceride level decreased from 36.82 to 7.27mmol/L, representing an 80% reduction from baseline. Total cholesterol decreased by 59% on average, and LDL levels decreased by 69%. Statistically significant differences were observed in triglyceride and cholesterol levels before and after treatment. Four patients exhibited increased HDL levels post-treatment, while one patient showed a decrease. The average HDL/TC level was 21% higher after treatment. CONCLUSION: LA in HTG-AP effectively improves clinical symptoms, rapidly lowers lipid levels, and achieves good therapeutic outcomes.

The relationship between depression and benign prostatic hyperplasia in middle-aged and elderly men in India: a large-scale population study.

BACKGROUND: There have been few investigations on the association between depression and benign prostatic hyperplasia (BPH). This study aims to explore the correlation between depression and BPH among middle-aged and older men in India. METHODS: We utilized data from male individuals aged 45 years and older who participated in the initial wave (2017-2018) of the Longitudinal Aging Study in India (LASI). The presence of BPH symptoms was based on self-reported information, while depressive symptoms were evaluated using CESD-10. The analysis was a cross-sectional study conducted on a final sample size of 30,108 male participants. To examine associations, we employed multivariate logistic regression analysis along with subgroup analysis and interaction tests. RESULTS: A total of 439 (1.46%) men reported BPH and had a higher depression score (10.18 ± 4.22 vs. 9.28 ± 4.00). The findings indicated a significant association between the depression score and the likelihood of developing BPH, even after accounting for all potential confounding variables (OR = 1.054, 95% CI: 1.030-1.078, p < 0.00001). The participants were then categorized into a depression group and a normal group based on their CESD-10 score, using a threshold of 10 to ascertain the existence or nonexistence of depression. After adjusting for all variables in model IV, the findings continued to exhibit statistical significance (OR = 1.611, CI: 1.327-1.955, p < 0.00001). Significant interaction effects of age, education level, caste or tribe, and alcohol consumption were observed (p for interaction < 0.05). CONCLUSION: Our research found that BPH was significantly linked to the presence of depressive symptoms among middle-aged and elderly Indian men. Additional prospective research is necessary to clarify this association and investigate potential mechanisms.

Causes of death among patients with testicular cancer during the survivorship.

OBJECTIVE: The aim was to evaluate the causes of death for patients with testicular cancer (TC), and calculate mortality risks for each cause. METHODS: Patients diagnosed between 2000 and 2017 were identified. Main causes of death including TC, second malignant tumor (SMT) and non-tumor diseases, and the standardized mortality rate (SMR) of each cause were analyzed. RESULTS: 27,143 patients with localized TC were included, and 1171 of them died including 215 TC deaths, 236 SMT deaths, and 720 non-tumor deaths. Main SMT deaths were cancer from lung and bronchus, colon and rectum, etc. Main non-cancer causes were diseases of heart, accidents and adverse effects and suicide and self-inflicted injury. Compared with the general population, the mortality risks from diseases of heart and accidents and adverse effects were significantly reduced. For 11,719 patients with regional and distant metastasis TC, 1733 died including 964 TC deaths, 345 SMT deaths and 424 non-tumor deaths. The main SMT and non-tumor deaths were lung and bronchus, diseases of heart and suicide and self-inflicted injury. CONCLUSION: The leading causes of death besides TC were lung and bronchus cancer, colon and rectum cancer, diseases of heart, accidents and adverse effects, suicide and self-inflicted injury for TC patients. The localized TC patients were associated with similar risks of SMT deaths and lower risks of main non-tumor causes of death. IMPACT: We evaluated all causes of death of TC patients and SMR for each cause of death. Our results could provide valuable information about the priority of healthcare during testicular cancer survival.

[Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma].

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.

Research Progress of Design Drugs and Composite Biomaterials in Bone Tissue Engineering.

Bone, like most organs, has the ability to heal naturally and can be repaired slowly when it is slightly injured. However, in the case of bone defects caused by diseases or large shocks, surgical intervention and treatment of bone substitutes are needed, and drugs are actively matched to promote osteogenesis or prevent infection. Oral administration or injection for systemic therapy is a common way of administration in clinic, although it is not suitable for the long treatment cycle of bone tissue, and the drugs cannot exert the greatest effect or even produce toxic and side effects. In order to solve this problem, the structure or carrier simulating natural bone tissue is constructed to control the loading or release of the preparation with osteogenic potential, thus accelerating the repair of bone defect. Bioactive materials provide potential advantages for bone tissue regeneration, such as physical support, cell coverage and growth factors. In this review, we discuss the application of bone scaffolds with different structural characteristics made of polymers, ceramics and other composite materials in bone regeneration engineering and drug release, and look forward to its prospect.

Second malignant tumors and non-tumor causes of death for patients with localized and regional kidney cancer after diagnosis.

BACKGROUND: To evaluate the second malignant tumors (SMTs) and non-tumor causes of death among patients diagnosed with localized and regional kidney cancer. METHODS: Patients diagnosed with kidney cancer between 2000 and 2017 in the Surveillance, Epidemiology, and End Results (SEER) program database were identified. All causes of death for patients during the follow-up and standardized mortality ratio (SMR) were analyzed. RESULT: 113,734 patients with localized kidney cancer with 30,390 cases of death were analyzed. 60.4% of the death cases were due to non-tumor caused and 23.6% were second malignant tumors (SMTs). Main SMTs included cancers of lung and bronchus [n = 1,283, SMR: 1.00 (0.95-1.06)] and pancreas [n = 393, SMR: 1.27 (1.15-1.41)]. Causes of death for non-tumor mainly included heart diseases [n = 6,161, SMR: 1.25 (1.21-1.28)] and chronic obstructive pulmonary disease (COPD) [n = 1,185, SMR: 0.99 (0.94-1.05)]. 14,437 of 29,602 patients with regional kidney cancer died. 14.6% of all deaths were due to SMTs and 23.6% due to non-tumor causes. Main SMTs contained bladder cancer [n = 371, SMR: 10.90 (9.81-12.06)] and lung and bronchus cancer [n = 346, SMR: 1.21 (1.08-1.34)]. The main non-tumor death was heart disease [n = 1,424, SMR: 1.26 (1.2-1.33)]. When stratified by pathological types, patients with clear cell renal cell carcinoma (RCC) did not have increased mortality risks of bladder cancer and lung cancer but patients with non-clear cell RCC did. CONCLUSION: SMTs and non-tumor diseases including lung and bronchus cancer, bladder cancer, pancreas cancer, diseases of heart, COPD, and cerebrovascular diseases are the leading causes of death besides kidney cancer and should be paid more attention during patients' survival period.

Effects of Curcumin on Axon Growth and Myelin Sheath Formation in an In Vitro Model.

Although the beneficial effects of curcumin, extracted from rhizomes of the ginger family genus Curcuma, on the repair and regeneration of nerves have been evaluated in vitro, there are few studies concerning its effects on axon myelination. Here, we used pheochromocytoma cells as an in vitro model of peripheral nerves. Pheochromocytoma cells were cultured alone or cocultured with Schwann cells and treated with increasing concentrations of curcumin. Cell growth was observed, and the expression levels of growth-associated protein 43 (GAP-43), microtubule-associated protein 2 (MAP-2), myelin basic protein (MBP), myelin protein zero (MPZ), Krox-20, and octamer binding factor 6 (Oct-6) were quantified. We found a significant increase in expression of all six proteins following curcumin treatment, with a corresponding increase in the levels of MBP, MPZ, Krox-20, and Oct-6 mRNA. Upregulation was greater with increasing curcumin concentration, showing a concentration-dependent effect. The results suggested that curcumin can promote the growth of axons by upregulating the expression of GAP-43 and MAP-2, stimulate synthesis and secretion of myelin-related proteins, and facilitate formation of the myelin sheath in axons by upregulating the expression of Krox-20 and Oct-6. Therefore, curcumin could be widely applied in future strategies for the treatment of nerve injuries.

Risk evaluation of adverse aortic events in patients with non-circular aortic annulus after transcatheter aortic valve implantation: a numerical study.

Transcatheter aortic valve implantation (TAVI) is a micro-invasive surgery used to treat patients with aortic stenosis (AS) efficiently. However, the uneven valve expansion can cause a non-circular annulus, which is one of the main factors leading to complications after TAVI. As a preliminary work, the main purpose of this study was to evaluate the risk of adverse aortic events in patients with a non-circular aortic annulus after TAVI. This study numerically investigated the distribution of four wall shear stress (WSS)-based indicators and three helicity-based indicators in eight patient-specific aortas with different annulus including circular, type I elliptical and type II elliptical shapes. Both elliptical annulus features can significantly enhance the intensity of the helicity (h2) in the ascending aorta (p < 0.001). However, for the type I elliptical annulus, the spiral flow structure was changed into low-velocity and disturbed flow pattern close to the inner side of the aortic arch. For the type II elliptical annulus, the spiral flow remained but became skewed in distribution. The elliptical annulus feature could increase the general level WSS-based indicators, especially in the ascending aorta. However, due to the disturbance of spiral flow or second helical flow in ascending aortas, areas with low TAWSS accompanied by high oscillatory shear index (OSI) and cross flow index (CFI) were observed in all the ascending aortas with non-circular annulus. The elliptical annulus feature can change the hemodynamic environment in the aortic arch, especially in the ascending aorta. Although both elliptical annulus features enhanced the strength of helicity, the uniform distribution of the helical flow was disturbed, especially in the ascending aorta, indicating the potential risk of adverse aortic events may increase. Therefore, for the patients without paravalvular leak but elliptical annulus shape after TAVI treatment, surgeons may be needed to consider further dilatation to make the non-circular annulus become circular.

Attenuating lipid metabolism in atherosclerosis: The potential role of Anti-oxidative effects on low-density lipoprotein of herbal medicines.

Atherosclerosis (AS) is a multifactorial chronic disease with great harm to the health of human being, which is a basic pathogenesis of many cardiovascular diseases and ultimately threatens human life. Abnormal blood lipid level is one of the most common diagnostic indicators of AS in clinic, and lipid metabolism disorder is often observed in patients with AS. Cholesterol is an important lipid in the human body, which is of great significance for maintaining normal life activities. Generally, cholesterol is transported to peripheral tissues by low-density lipoprotein (LDL), and then transported to the liver by high-density lipoprotein (HDL) via its cholesterol reverse transport function, and finally discharged. Under oxidative stress condition, LDL is commonly oxidized to the form ox-LDL, which is ingested by macrophages in large quantities and further forms foam cells, disrupting the normal metabolic process of cholesterol. Importantly, the foam cells are involved in forming atherosclerotic plaques, whose rupture may lead to ischemic heart disease or stroke. Furthermore, ox-LDL could also promote the development of AS by damaging vascular endothelium, promoting the migration and proliferation of smooth muscle cells, and activating platelets. Therefore, inhibiting LDL oxidation may be an effective way to improve lipid metabolism and prevent AS. In recent years, increasing studies have shown that herbal medicines have great potentiality in inhibiting LDL oxidation and reducing ox-LDL induced foam cell formation. Accordingly, this paper summarized current research on the inhibitory effects of herbal medicines against LDL oxidation and foam cell formation, and made a brief description of the role of cholesterol and LDL in lipid metabolism disorder and AS pathogenesis. Importantly, it is suggested that herbal medicines could inhibit LDL oxidation and regulate cholesterol homeostasis via downregulation of CD36 and SR-A, whereas upregulation of ABCA1 and ABCG1.

Prognostic Significance of a Model Based on Acetaldehyde Dehydrogenase 2 Genetic Polymorphisms in Laryngeal Carcinoma.

OBJECTIVE: Because of the high costs associated with early-stage laryngeal carcinoma diagnosis and prognosis prediction, this study attempts to find valuable targets to establish a novel predictive model by focusing on the aldehyde dehydrogenase 2 (ALDH2) genotype and other peripheral blood markers. STUDY DESIGN: Retrospective study. SETTING: Tertiary comprehensive hospital. METHODS: From January 2011 to January 2021, 362 cases of laryngeal carcinoma were included and divided into 2 groups in this retrospective analysis. Information on medical history, alcohol, and tobacco consumption habits, ALDH2 genotypes, and other peripheral blood markers was collected. Endpoints of the current study included disease-free survival and overall survival. A nomogram model for overall survival was established and evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 236 patients were included in the training cohort, and the other 126 were included in the validation cohort. The median follow-up of the patients was 9.6 years (interquartile range: 7.5-12.5 years). Peripheral fibrinogen, hemoglobin, and ALDH2 genotypes were significantly associated with an increase in laryngeal carcinoma mortality rate on Kaplan-Meier curves. The ROC curve showed that the effectiveness of overall survival prediction by the nomogram model was better than that of traditional clinical staging. CONCLUSION: A prognostic nomogram of laryngeal carcinoma patients involving ALDH2 and peripheral blood markers and T and N stages was constructed and validated.

Comparative analysis of the chrysanthemum transcriptome with DNA methylation inhibitors treatment and silencing MET1 lines.

BACKGROUND: As one of the ten most famous flowers in China, the chrysanthemum has rich germplasm with a variety of flowering induction pathways, most of which are photoperiod-induced. After treatment with DNA methylation inhibitors, it was found that DNA methylation plays an important role in flowering regulation, but the mechanism of action remains unclear. Therefore, in this study, curcumin, 5-azaC, their mixed treatment, and MET1-RNAi lines were used for transcriptome sequencing to find out how different treatments affected gene expression in chrysanthemums at different stages of flowering. RESULTS: Genomic DNA methylation levels were measured using HPLC technology. The methylation level of the whole genome in the vegetative growth stage was higher than that in the flowering stage. The methylation level of DNA in the vegetative growth stage was the lowest in the curcumin and mixed treatment, and the methylation level of DNA in the transgenic line, mixed treatment, and curcumin treatment was the lowest in the flowering stage. The flowering rate of mixed treatment and curcumin treatment was the lowest. Analysis of differentially expressed genes in transcriptomes showed that 5-azaC treatment had the most differentially expressed genes, followed by curcumin and transgenic lines, and mixed treatment had the fewest. In addition, 5-azaC treatment resulted in the differential expression of multiple DNA methylation transferases, which led to the differential expression of many genes. Analysis of differentially expressed genes in different treatments revealed that different treatments had gene specificity. However, the down-regulated GO pathway in all 4 treatments was involved in the negative regulation of the reproductive process, and post-embryonic development, and regulation of flower development. Several genes associated with DNA methylation and flowering regulation showed differential expression in response to various treatments. CONCLUSIONS: Both DNA methylase reagent treatment and targeted silencing of the MET1 gene can cause differential expression of the genes. The operation of the exogenous application is simple, but the affected genes are exceedingly diverse and untargeted. Therefore, it is possible to construct populations with DNA methylation phenotypic diversity and to screen genes for DNA methylation regulation.

Role of immune-inflamed phenotype in the prognosis of hypopharyngeal carcinoma following primary surgery.

BACKGROUND: The immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined. METHODS: We enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand-1 (PD-L1), and interferon (IFN)-γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non-inflamed tumors based on the presence or absence of parenchymal CD8+ T cells. RESULTS: We found that 74% of HPSCC cases in our cohort were characterized by an immune-inflamed TME. Immune-inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163+ tumor-associated macrophages and Foxp3+ regulatory T cells. Additionally, the inflamed tumor showed increased expression of PD-L1, without IFN-γ upregulation. CONCLUSIONS: The immune-inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment.