Hypothesis paper: GDF15 demonstrated promising potential in Cancer diagnosis and correlated with cardiac biomarkers.

BACKGROUND: Cardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction). METHODS: Analysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG). RESULTS: GDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort. CONCLUSION: GDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.

Tumor-exosomal miR-205-5p as a diagnostic biomarker for colorectal cancer.

BACKGROUND: Tumor-derived exosomal miRNAs play crucial roles in cancer diagnosis. Current studies aim to identify exosomal miRNAs associated with colorectal cancer (CRC) that are noninvasive, sensitive, and specific. PATIENTS AND METHODS: Exosomes were extracted from CRC patients and healthy donors via ultracentrifugation, followed by verification via transmission electron microscopy (TEM), qNano, and Western blot analysis. The differential expression levels and clinical characteristics of miR-205-5p were analyzed in CRC via data from The Cancer Genome Atlas (TCGA). Real-time quantitative PCR was used to assess the expression levels of exosomal miRNAs in 157 primary CRC patients, 20 patients with benign diseases, and 135 healthy donors. Predictions regarding target genes were made to guide further exploration of the disease's etiopathogenesis through bioinformatics. RESULTS: Compared with that in healthy donors, the expression of miR-205-5p in colorectal cancer (CRC) patients was significantly lower, as determined through analysis of the TCGA database. We conducted a prediction and analysis of the functional enrichment of downstream target genes regulated by miR-205-5p. A lower level of exosomal miR-205-5p in the serum of CRC patients than in that of healthy controls (p < 0.0001) and patients with benign disease (p < 0.0001) was observed. Furthermore, the expression levels of exosomal miR-205-5p were significantly lower in early-stage CRC patients than in the comparison groups (p<0.001 and p < 0.0001). Notably, the expression levels of exosomal miR-205-5p significantly increased postoperatively (p = 0.0053). CONCLUSIONS: The present study demonstrated that serum exosomal miR-205-5p may be a diagnostic biomarker for CRC.

Ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis: a case report.

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Preliminary feasibility assessment of a targeted, pharmacist-led intervention for older adults with polypharmacy: a mixed-methods study.

BACKGROUND: Polypharmacy is associated with the prescription of inappropriate medications and avoidable medication-related harm. A novel pharmacist-led intervention aims to identify and resolve inappropriate medication prescriptions in older adults with polypharmacy. AIM: To conduct a preliminary feasibility assessment of the intervention in primary care, testing whether specific components of the intervention procedures and processes can be executed as intended. METHOD: The mixed-methods study was approved by the New Zealand Health and Disability Ethics Committees and public health agency. Patients from a New Zealand general practice clinic were recruited over 4 weeks to receive the intervention. The preliminary feasibility assessment included measures of intervention delivery, patient-reported outcome measures, and perspectives from ten patients and six clinicians. Data were analysed quantitatively and qualitatively to determine if a full-scale intervention trial is warranted. The study's progression criteria were based on established research and guided the decision-making process. RESULTS: The intervention met the study's progression criteria, including patient recruitment, retention, and adherence to the intervention procedures. However, several modifications were identified, including: (1) enhancing patient recruitment, (2) conducting a preliminary meeting between the patient and pharmacist, (3) supporting pharmacists in maintaining a patient-centred approach, (4) reviewing the choice of patient-reported outcome measure, (5) extending the 8-week follow-up period, (6) allocating more time for pharmacists to conduct the intervention. CONCLUSION: The study found the intervention feasible; however, additional development is required before progressing to a full-scale trial. This intervention has the potential to effectively reduce medication-related harm and improve outcomes for older adults with polypharmacy. TRIAL REGISTRATION NUMBER: ACTRN12621000268842 Date registered: 11/03/2021.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study.

Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Diagnostic value of inflammatory indicators for surgical site infection in patients with breast cancer.

Background: Breast cancer is the most commonly diagnostic cancer in women worldwide. The main treatment for these patients is surgery. However, there is a high incidence of surgical site infection (SSI) in breast cancer patients. The aim of this study was to identify effective infection-related diagnostic markers for timely diagnosis and treatment of SSI. Methods: This retrospective study included 263 breast cancer patients who were treated between July 2018 and March 2023 at the Shandong Cancer Hospital and Institute. We analyzed differences between the SSI group and control group and differences before and during infection in the SSI group. Finally, we tested the distribution of pathogenic microorganisms and their susceptibility to antibiotics. Results: Compared with preoperative inflammatory indicators, white blood cells (WBC), neutrophils (NEU), absolute neutrophil count to the absolute lymphocyte count (NLR), D2 polymers (D-Dimer) and fibrinogen (FIB) were significantly increased, while lymphocytes (LYM), albumin (ALB) and prealbumin (PA) were significantly decreased in the SSI group. Compared with uninfected patients, WBC, NEU, NLR and FIB were significantly increased, ALB and PA were significantly decreased in SSI patients, while LYM and D-Dimer did not differ significantly. The distribution of infection bacteria in SSI patients showed that the proportion of patients with Staphylococcus aureus infection was as high as 70.41%; of those patients, 19.33% had methicillin-resistant Staphylococcus aureus (MRSA) infection. The area under the curves (AUCs) of the receiver operating curves (ROCs) for WBC, NEU, NLR, FIB, ALB and PA were 0.807, 0.811, 0.730, 0.705, 0.663 and 0.796, respectively. The AUCs for other inflammatory indicators were not statistically significant. There was no significant difference in antibiotic resistance for Staphylococcus aureus when compared to that of gram-positive bacteria. The resistance of gram-positive bacteria to ceftriaxone (CRO), cefoxitin (FOX), chloramphenicol (CHL), minocycline (MNO) and tetracycline (TCY) was lower than that of gram-negative bacteria, while the resistance to gentamicin (GEN) was higher. Conclusion: This study demonstrated that WBC, NEU, NLR, FIB and PA have good predictive value for identifying patients at risk of SSI. The cut-off values of inflammatory indicators can be helpful in the prevention and diagnosis of SSI.

Increased 68 Ga-FAPI Activity in Primary Small Cell Neuroendocrine Carcinoma of the Gallbladder.

ABSTRACT: Primary small cell neuroendocrine carcinomas are extremely rare heterogeneous neoplasms. We present 68 Ga-FAPI (fibroblast activation protein inhibitor) PET/CT findings of small cell neuroendocrine carcinoma of the gallbladder in a 57-year-old woman. This rare gallbladder small cell neuroendocrine carcinoma demonstrated intense tracer uptake on 68 Ga-FAPI PET/CT. This demonstrates the potential value of 68 Ga-FAPI PET/CT for evaluation of gallbladder small cell neuroendocrine carcinoma.

Development and validation of PolyScan, an information technology triage tool for older adults with polypharmacy: a healthcare informatics study.

Introduction Polypharmacy is associated with potentially inappropriate medicine prescribing and avoidable medicine-related harm. Polypharmacy should not be perceived as inherently harmful. Instead, priority should be placed on reducing inappropriate prescribing. Aim The study aimed to develop and validate PolyScan, a primary care information technology tool, to triage older adults with polypharmacy who are prescribed potentially inappropriate medicines. Methods Twenty-one indicators from a New Zealand criteria of potentially inappropriate medicines to correct for older adults with polypharmacy were developed into a set of implementable definitions. The definitions were applied as algorithmic logic statements used to interrogate hospital and emergency department records and pharmaceutical collection data to classify whether each indicator was present at an individual patient level, and then triage individuals based on the number of indicators met. Validity was evaluated by comparing PolyScan's accuracy against a manual review of healthcare records for 300 older adults. Results PolyScan was successfully implemented as a tool that can be used to identify potentially inappropriate prescribing in older adults with polypharmacy at different levels of aggregation. The tool has utility for individual practitioners delivering patient care, primary care organisations undertaking quality improvement programmes, and policymakers considering system-level interventions for medicines-related safety. During the validity assessment, PolyScan identified nine individuals (3%) with polypharmacy and indicators of potentially inappropriate medicine. Five unique indicators were detected. PolyScan achieved 100% sensitivity, specificity, and positive and negative predictive values. Discussion PolyScan can support clinicians, clinics, and policymakers with allocation of resources, rational medicine campaigns, and identifying individuals prescribed potentially inappropriate medicines for review.

Augmented Reality Surgical Navigation System Integrated with Deep Learning.

Most current surgical navigation methods rely on optical navigators with images displayed on an external screen. However, minimizing distractions during surgery is critical and the spatial information displayed in this arrangement is non-intuitive. Previous studies have proposed combining optical navigation systems with augmented reality (AR) to provide surgeons with intuitive imaging during surgery, through the use of planar and three-dimensional imagery. However, these studies have mainly focused on visual aids and have paid relatively little attention to real surgical guidance aids. Moreover, the use of augmented reality reduces system stability and accuracy, and optical navigation systems are costly. Therefore, this paper proposed an augmented reality surgical navigation system based on image positioning that achieves the desired system advantages with low cost, high stability, and high accuracy. This system also provides intuitive guidance for the surgical target point, entry point, and trajectory. Once the surgeon uses the navigation stick to indicate the position of the surgical entry point, the connection between the surgical target and the surgical entry point is immediately displayed on the AR device (tablet or HoloLens glasses), and a dynamic auxiliary line is shown to assist with incision angle and depth. Clinical trials were conducted for EVD (extra-ventricular drainage) surgery, and surgeons confirmed the system's overall benefit. A "virtual object automatic scanning" method is proposed to achieve a high accuracy of 1 ± 0.1 mm for the AR-based system. Furthermore, a deep learning-based U-Net segmentation network is incorporated to enable automatic identification of the hydrocephalus location by the system. The system achieves improved recognition accuracy, sensitivity, and specificity of 99.93%, 93.85%, and 95.73%, respectively, representing a significant improvement from previous studies.

Development of explicit criteria identifying potentially inappropriate polypharmacy in older adults in New Zealand primary care: a mixed-methods study.

Introduction The link between polypharmacy, risk of potentially inappropriate medication exposure, and avoidable medicines-related harm is well recognised. Not all polypharmacy is harmful, and contemporary multimodal approaches to managing long-term conditions are evidence-based and commonplace. What is needed is a focus on reducing inappropriate medication prescribing in polypharmacy. Aim This study aims to develop the New Zealand criteria, a set of New Zealand-specific potentially inappropriate medication indicators to correct for older adults with polypharmacy. Methods A mixed-methods approach was used. An expert panel group comprising four clinical pharmacists, two general practitioners, one geriatrician, and two nurse practitioners generated a collection of ideas via the nominal group technique, which combined with published criteria from literature, provided the list of potential criteria. These potential criteria were reviewed, validated, and ranked for importance via a two-round modified Delphi analysis with the same panel. Results The nominal group technique generated 35 indicators, of which 23 were rated as important. Fifty-nine of 91 indicators from literature were rated as relevant and important. This generated 82 indicators for the modified Delphi analysis, from which 61 achieved consensus. Overall, 21 unique criteria were judged 'very important', 31 were judged 'important', and nine were judged 'somewhat important'. No indicators were judged 'low importance'. Discussion The New Zealand criteria provides 61 medication indicators, which New Zealand experts recommend should prompt formal, documented review. The criteria can be used to systematically identify patients at the highest risk of avoidable medication-related harm for proactive review.

Diagnostic value of procalcitonin, hypersensitive C-reactive protein and neutrophil-to-lymphocyte ratio for bloodstream infections in pediatric tumor patients.

OBJECTIVES: Bloodstream infection (BSI) is one of the major causes of death in pediatric tumor patients. Blood samples are relatively easy to obtain and thus provide a ready source of infection-related biological markers for the prompt evaluation of infection risk. METHODS: A total of 259 pediatric tumor patients were included from May 2019 to March 2022. Patients were divided into BSI group (n=70) and control group (n=189). Clinical and biological data were collected using electronic medical records. Differences in biological markers between BSI group and control group and differences before and during infection in BSI group were analyzed. RESULTS: The infected group showed higher levels of procalcitonin (PCT) and hypersensitive C-reactive-protein (hsCRP), and lower prealbumin (PA) than the uninfected group. Area under the receiver-operating curve (ROC) curves (AUC) of PCT, hsCRP and NLR (absolute neutrophil count to the absolute lymphocyte count) were 0.756, 0.617 and 0.612. The AUC of other biomarkers was ≤0.6. In addition, PCT, hsCRP, NLR and fibrinogen (Fg) were significantly increased during infection, while PA and lymphocyte (LYM) were significantly decreased. Antibiotic resistant of Gram-positive bacteria to CHL, SXT, OXA and PEN was lower than that of Coagulase-negative Staphylococcus. Resistant of Gram-positive bacteria to CHL was lower, while to SXT was higher than that of Gram-negative bacteria. CONCLUSIONS: This study explored the utility of biomarkers to assist in diagnosis and found that the PCT had the greatest predictive value for infection in pediatric tumor patients with BSI. Additionally, the PCT, hsCRP, NLR, PA, LYM and Fg were changed by BSI.

Optimized low-dose positron emission tomography/computed tomography schemes in pediatric tumor patients: a randomized clinical trial.

Background: It's clinically relevant to reduce the radiation dose to children while ensuring their positron emission tomography/computed tomography (PET/CT) image quality. The optimal protocol for whole-body PET/CT imaging in children (non-model) has been less studied. In this study, we investigated the optimal protocol for PET/CT imaging of pediatric oncology by analyzing the radiation dose and image quality in18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT imaging of children with oncology. Methods: One hundred children with tumors who underwent 18F-FDG PET/CT were included. CT grouping: randomly divided into 18 groups A-R according to the combination of three parameters: tube voltage (80/120 kV), automatic milliamp range (20-39/40-59/60-80 mA), and noise index (NI) (8/12/14). PET grouping: randomly divided into 9 groups a-i according to the combination of two parameters: the pharmaceuticals injection dose (0.08/0.12/0.15 mCi/kg) and time per bed (120/150/180 s). The effective radiation dose (ED) was calculated separately for each group and the image quality of CT and PET was evaluated subjectively using standard deviation (SD) and coefficient of variation (CV) objective evaluation and 5-point evaluation method, respectively. Results: Ninety-seven images in CT and 57 images in PET were included. The best quality of CT images was in group K (120 kV/40-59 mA/8); there are 9 groups had good image quality and lower dose length product (DLP) than group K (SD ±10), while the difference in DLP between groups was large. The Kruskal-Wallis (K-W) test showed that the difference in image quality between the 9 groups was not statistically significant. The best PET image quality was in group i [0.15 (mCi/kg)/180 s]; there are four groups had good image quality and lower EDPET than group i (CV ±3.5%), while the difference in EDPET between groups was large (4.4-6.5 mSv), and the K-W test showed that the difference in image quality between the four groups was not statistically significant (P>0.05), with the lowest EDPET being in the g group. Conclusions: The optimal protocols for CT scanning and PET imaging in this experiment were group H (80 kV/40-59 mA/14) and group g [0.08 (mCi/kg)/180 s], respectively.Trial Registration: Chinese Clinical Trial Registry ChiCTR2200061386.

The value of the SUV ratio between lymph node and bone marrow in predicting pelvic lymphatic metastasis of patients with locally advanced cervical cancer: an integrated PET/CT study.

PURPOSE: This study aimed to evaluate the value of the standardized uptake value (SUV) ratio between lymph nodes and bone marrow (BM) measured by Fluorine-18-fluorodeoxyglucose PET and computed tomography ( 18 F-FDG PET/CT) for predicting pelvic lymph node (PLN) metastasis in patients with locally advanced cervical cancer (LACC). MATERIALS AND METHODS: A total of 62 patients with pathological stage Ib-IVa cervical cancer who underwent 18 F-FDG PET/CT before treatment were reviewed retrospectively. We measured the metabolic and morphological parameters of lymph nodes and primary tumors, bone marrow SUV (SUVBM) and calculated the ratio of lymph nodes maximum SUV (SUVmax) to bone marrow SUV (SUVLN/BM) and the ratio of short-axis diameter to long-axis diameter (Ds/l) of lymph nodes. A receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic efficacy of each parameter. RESULTS: There were 180 lymph nodes with pathological evidence included in the study. Our results indicated that Ds/l, SUVmax of lymph nodes (SUVLN) and SUVLN/BM were independent risk factors for PLN metastasis in LACC ( P < 0.05), and SUVLN/BM showed the best diagnostic performance by ROC curve analysis. The SUVBM in the anemia group was significantly higher than that in the nonanemia group (3.05 vs. 2.40, P < 0.05); furthermore, false-positive cases decreased when the SUVLN/BM was used as the diagnostic criterion instead of SUVLN, especially in the anemia group. ROC curve analysis showed that the area under the curve value of the combination of SUVLN/BM and Ds/l was 0.884 ( P < 0.05), which was higher than Ds/l or SUVLN/BM alone. CONCLUSIONS: SUVLN/BM could improve the ability to predicting PLN metastasis in patients with LACC, and the diagnostic efficacy of the combination of SUVLN/BM and Ds/l might be better than that of a single parameter.

Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy.

AIMS: To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome. METHODS AND RESULTS: In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%). CONCLUSION: Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

Effects of puerarin on chronic inflammation: Focus on the heart, brain, and arteries.

Age-associated increases in physical and mental stress, known as allostatic load, could lead to a chronic low-grade inflammation in the heart, brain, and arteries. This low-grade inflammation potentially contributes to adverse structural and functional remodeling, such as intimal medial thickening, endothelial dysfunction, arterial stiffening, cardiac hypertrophy and ischemia, and cognitive decline. These cellular and tissue remodeling is the fertile soil for the development of age-associated structural and functional disorders in the cardiovascular and cerebrovascular systems in the pathogenesis of obesity, type II diabetes, hypertension, atherosclerosis, heart dysfunction, and cognitive decline. Growing evidence indicates that puerarin, a polyphenol, extracted from Puerara Labota, efficiently alleviates the initiation and progression of obesity, type II diabetes, hypertension, atherosclerosis, cardiac ischemia, cardiac arrythmia, cardiac hypertrophy, ischemic stroke, and cognition decline via suppression of oxidative stress and inflammation. This mini review focuses on recent advances in the effects of puerarin on the oxidative and inflammatory molecular, cellular, tissue events in the heart, brain, and arteries.

Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis.

BACKGROUND: In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown. METHODS: We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies. FINDINGS: Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53-0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38-0·70), revascularisation (0·54, 0·36-0·80), stroke (0·59, 0·45-0·78), and cardiovascular death (0·65, 0·52-0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001). INTERPRETATION: Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors. FUNDING: Population Health Research Institute.

Fractionated Irradiation Enhances Invasion and Migration by Inducing Epithelial-Mesenchymal Transition and Stemness-Like Properties in A549 Cells.

OBJECTIVE: Radioresistance-induced locoregional recurrence remains a major cause of low survival rates. However, the mechanism of treatment failure in these lung cancer patients has not been determined. In the current study, we tried to explore the potential molecular mechanism. METHODS: The fractionated irradiations were continued until the total concentration reached 80 Gy, and we established radioresistant subclones derived from A549 lines (designated as A549/R). The MTT assay, wound healing assay, transwell assay, and soft agar colony formation assay were employed to detect the proliferation, migration, invasion, and clonogenicity of the cells, respectively. Western blot and Fluorescence Activating Cell Sorter (FACS) indicated the expression of the markers. RESULTS: A549/R cells proliferated more slowly than the parental A549 cells. A significant acceleration in cell migration and invasion was revealed in A549/R cells compared with A549 cells. The expression levels of mesenchymal markers (N-cadherin, vimentin, claudin-1, and Snail) increased, while epithelial markers (E-cadherin and ß-catenin) decreased in A549/R cells. Meanwhile, the expression levels of stemness markers (Oct4, Notch1, and CD133) increased in A549/R cells, and A549/R cells showed more sphere-forming activity compared with A549 cells. CONCLUSION: Fractionated irradiation could promote epithelial-mesenchymal transition and enhance the migration, invasion, and stemness-like properties in A549 cells, elucidating the possible radioresistance mechanisms of the cancer cells.

The diagnostic value of metabolic, morphological and heterogeneous parameters of 18F-FDG PET/CT in mediastinal lymph node metastasis of non-small cell lung cancer.

OBJECTIVES: To investigate the value of PET/CT metabolic, morphological and heterogeneous parameters in the diagnosis of 18F-FDG positive mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 156 patients with pathologically diagnosed NSCLC and underwent 18F-FDG PET/CT scans were enrolled in this study. Mediastinal lymph nodes with 18F-FDG uptake greater than the mediastinum were analyzed. The metabolic parameters of maximum and mean standardized uptake value (SUVmax, SUVmean), SUVratio (node SUVmax/mediastinum SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), morphological parameters of maximum short diameter (Dmin), CT values and metabolic heterogeneity parameter of coefficient of variation (COV) were measured. The performance of each parameter and their combinations for diagnosis of lymph node metastasis was evaluated through receiver operating characteristic (ROC) curves and binary logistic regression analysis. RESULTS: There were 206 lymph nodes with pathological evidence included in the study, including 103 metastatic and 103 nonmetastatic nodes. The SUVmax, SUVmean, SUVratio, TLG, COV and Dmin of metastatic lymph nodes were significantly higher/greater than those in nonmetastatic ones (P < 0.05). ROC curve analysis revealed that the combination of SUVratio, Dmin and COV showed the highest diagnostic efficacy among all single and combined parameters, the area under the curve (AUC) was 0.907 (P = 0.000), these three parameters all increased the risk of lymph node metastasis, with odds ratios of 1.848, 1.293 and 1.258, respectively (all P < 0.05). CONCLUSION: Heterogeneity parameter was helpful for the accurate distinction of mediastinal lymph node metastasis in NSCLC. The combination of the SUVratio, Dmin and COV could improve the diagnostic accuracy. Multiple-parameters analysis plays an important complementary role in the diagnosis of lymph node metastasis.

Histone demethylase KDM2A: Biological functions and clinical values (Review).

Histone lysine demethylation modification is a critical epigenetic modification. Lysine demethylase 2A (KDM2A), a Jumonji C domain-containing demethylase, demethylates the dimethylated H3 lysine 36 (H3K36) residue and exerts little or no activity on monomethylated and trimethylated H3K36 residues. KDM2A expression is regulated by several factors, such as microRNAs, and the phosphorylation of KDM2A also plays a vital role in its function. KDM2A mainly recognizes the unmethylated region of CpG islands and subsequently demethylates histone H3K36 residues. In addition, KDM2A recognizes and binds to phosphorylated proteins, and promotes their ubiquitination and degradation. KDM2A plays an important role in chromosome remodeling and gene transcription, and is involved in cell proliferation and differentiation, cell metabolism, heterochromosomal homeostasis and gene stability. Notably, KDM2A is crucial for tumorigenesis and progression. In the present review, the documented biological functions of KDM2A in physiological and pathological processes are comprehensively summarized.