The association between blood test trends and undiagnosed cancer: a systematic review and critical appraisal

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient’s individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence

Formyl-methionyl-leucyl-phenylalanine–Induced Dopaminergic Neurotoxicity via Microglial Activation: A Mediator between Peripheral Infection and Neurodegeneration?

BackgroundParkinson disease (PD), a chronic neurodegenerative disease, has been proposed to be a multifactorial disorder resulting from a combination of environmental mechanisms (chemical, infectious, and traumatic), aging, and genetic deficits. Microglial activation is important in the pathogenesis of PD.ObjectivesWe investigated dopaminergic (DA) neurotoxicity and the underlying mechanisms of formyl-methionyl-leucyl-phenylalanine (fMLP), a bacteria-derived peptide, in relation to PD. METHODS: We measured DA neurotoxicity using a DA uptake assay and immunocytochemical staining (ICC) in primary mesencephalic cultures from rodents. Microglial activation was observed via ICC, flow cytometry, and superoxide measurement.ResultsfMLP can cause selective DA neuronal loss at concentrations as low as 10−13 M. Further, fMLP (10−13 M) led to a significant reduction in DA uptake capacity in neuron/glia (N/G) cultures, but not in microglia-depleted cultures, indicating an indispensable role of microglia in fMLP-induced neurotoxicity. Using ICC of a specific microglial marker, OX42, we observed morphologic changes in activated microglia after fMLP treatment. Microglial activation after fMLP treatment was confirmed by flow cytometry analysis of major histocompatibility antigen class II expression on a microglia HAPI cell line. Mechanistic studies revealed that fMLP (10−13 M)-induced increase in the production of extracellular superoxide from microglia is critical in mediating fMLP-elicited neurotoxicity. Pharmacologic inhibition of NADPH oxidase (PHOX) with diphenylene-iodonium or apocynin abolished the DA neurotoxicity of fMLP. N/G cultures from PHOX-deficient (gp91PHOX−/ −) mice were also insensitive to fMLP-induced DA neurotoxicity.ConclusionfMLP (10−13 M) induces DA neurotoxicity through activation of microglial PHOX and subsequent production of superoxide, suggesting a role of fMLP in the central nervous system inflammatory process

Changes in body weight and cardiovascular risk factors in a Chinese population with type 2 diabetes mellitus: a longitudinal study

IntroductionThe primary care management of blood glucose, blood pressure, lipid profiles, and body weight is important among patients with type 2 diabetes mellitus (T2DM) to prevent disease progression. Information on how weight changes would improve or deteriorate cardiovascular (CV) risk factors is warranted for making primary care recommendations. We aimed to investigate the changes in body weight and CV risk factors and to analyse their association in a Chinese population with T2DM.MethodsWe retrieved longitudinal data between 2020 and 2021 from 1,758 adult primary care patients enrolled in a diabetic retinopathy (DR) screening programme. Linear associations of changes in body weight with CV risk factors were explored. Multivariable logistic regression analysis was performed to examine associations between different weight change categories and the worsening of CV risk factors.ResultsThe mean age of all the participants was 63.71 years, and over half of participants were females. During a one-year follow-up period, 24.7% of patients had a weight loss of ≥3%, while 22.2% of patients had a weight gain of ≥3%. Patients who had a weight loss of ≥3% were more likely to prevent the worsening of haemoglobin A1c (HbA1c) and triglycerides, while those who had a weight gain of ≥3% tended to have worsened HbA1c, lipid profiles, and blood pressure.ConclusionResults from this real-world investigation suggested the concurrent need for weight loss intervention among patients who are overweight or obese and weight gain prevention among patients whose body weight falls within the normal range in the context of community-based diabetes management

Over-Expression of PDGFR-β Promotes PDGF-Induced Proliferation, Migration, and Angiogenesis of EPCs through PI3K/Akt Signaling Pathway

The proliferation, migration, and angiogenesis of endothelial progenitor cells (EPCs) play critical roles in postnatal neovascularization and re-endothelialization following vascular injury. Here we evaluated whether the over-expression of platelet-derived growth factor receptor-β (PDGFR-β) can enhance the PDGF-BB-stimulated biological functions of EPCs through the PDGFR-β/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We first confirmed the expression of endogenous PDGFR-β and its plasma membrane localization in spleen-derived EPCs. We then demonstrated that the PDGFR-β over-expression in EPCs enhanced the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. Using AG1295 (a PDGFR kinase inhibitor), LY294002 (a PI3K inhibitor), and sc-221226 (an Akt inhibitor), we further showed that the PI3K/Akt signaling pathway participates in the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. In addition, the PI3K/Akt signaling pathway is required for PDGFR-β over-expression to enhance these PDGF-BB-induced phenotypes

Survival benefit of surgical treatment for patients with stage IVB endometrial cancer: a propensity score-matched SEER database analysis

The study aimed to evaluate the value of cancer-directed surgery (CDS) in improving the prognosis of patients with stage IVB endometrial cancer (EC) and under which kind of conditions could maximise its value. The Surveillance, Epidemiology, and End Results database was used to analyse patients diagnosed with stage IVB EC who received chemotherapy between 2004 and 2016. Among 1978 patients were enrolled following propensity score matching (PSM). We found that CDS was closely associated with prolonged overall survival. Moreover, CDS can effectively improve the survival rate of patients with protective or unfavourable factors and should be considered in a range of circumstances. Almost all patients (96.15%) who received surgery were operated on primary tumours of the reproductive organs and obtained favourable surgical outcomes. In conclusion, surgery can improve the survival of patients with stage IVB EC, palliative hysterectomy is worth considering in such patients.IMPACT STATEMENT What is already known on this subject? Patients with stage IVB EC account for a small proportion, so previous researches usually had an insufficient sample size. And it is still controversial whether to perform surgery on patients with stage IVB EC. What do the results of this study add? We verified the value of CDS in improving prognosis of patients with stage IVB EC. We also found that surgery outcomes were better in patients aged ˂ 60 years, and with T1 and T2 invasion. Moreover, resection of the primary site played an important role in prolonging survival time. What are the implications of these findings for clinical practice and/or further research? Surgical treatment can prolong the overall survival of patients with stage IVB EC, even if only primary site resection is performed. Surgery should be more aggressive in patients aged ˂ 60 years, and with lesions confined in the pelvis (with T1 and T2 invasion). The survival rate of patients with brain metastasis may also be improved by surgery. However, because of the small sample size, the surgical benefit needs further confirmation

Exploring Water-and-Land-Adapted Spatial Layout of Crop Planting in North China

North China has specific regional advantages in the overall economic and social development of China, and water resources are the most prominent factor that affects the sustainable development of this region. This study focuses on the land spatial layout of water-and-land adapted planting in North China. Based on the analysis of agricultural planting structure and water and land resource layout in the current year (2018) of North China, and considering varied population, climate, and socio-economic scenarios and water resource constraints, the study proposes a scheme for optimizing the agricultural planting layout in North China that adapts to local water and land resource conditions. We suggest that the burden on production and supply of commercial grain and other commercial agricultural products in North China should be appropriately reduced. In terms of improving the regional water resource carrying capacity, Hebei Province should alleviate its water shortage through water transfer. Shanxi Province should improve the agricultural water use efficiency through agricultural mechanization and modernization. Shandong Province and Henan Province can moderately fallow the land and improve forest and grass coverage. It is also recommended to optimize the spatial layout of agricultural planting and adjust the planting structure to adapt to water. In shallow groundwater overexploitation areas as well as Tianjin City and the southeast of Hebei Plain where deep groundwater overexploitation is severe, semi-arid land planting systems and structures that adapt to precipitation should be developed, and the specific recuperation period should be determined according to the rate of groundwater recharge

Boron-modified chlorine-free K+-FeOx/SBA-15 as highly effective catalyst for propylene epoxidation by nitrous oxide

Modification of chlorine-free alkali metal ion (K+, Rb+, or Cs+)-containing FeOx/SBA-15 catalysts with boron enhanced their catalytic performances in propylene epoxidation by nitrous oxide. A B-K+-FeOx/SBA-15 catalyst (K/Fe = 2.5, B/Fe = 0.5) showed the best propylene oxide (PO) formation activity, providing PO selectivities of 79 and 55% at propylene conversions of 4.8 and 13% at 350 and 400 degrees C, respectively

Functional significance of glycogen synthase kinase-3 regulation by serotonin

Serotonin modulates brain physiology and behavior and has major roles in brain diseases involving abnormal mood and cognition. Enhancing brain serotonin has been found to regulate glycogen synthase Kinase-3 (GSK3), but the signaling mechanism and functional significance of this regulation remain to be determined. In this study, we tested the signaling mechanism mediating 5-HT1A receptor-regulated GSK3 in the hippocampus. Using mutant GSK3 knock-in mice, we also tested the role of GSK3 in the behavioral effects of 5-HT1A receptors and the serotonin reuptake inhibitor fluoxetine. The results showed that activation of 5-HT1A receptors by 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) increased phosphorylation of the N-terminal serine of both GSK3α and GSK3β in several areas of the hippocampus. The effect of 8-OH-DPAT was accompanied by an increase in the active phosphorylation of Akt, and was blocked by LY294002, an inhibitor of phosphoinositide 3-kinases (PI3K). Phosphorylation of GSK3β, but not GSK3α, was necessary for 5-HT1A receptors to suppress the hippocampus-associated contextual fear learning. Furthermore, acute fluoxetine treatment up-regulated both phospho-Ser21-GSK3α and phospho-Ser9-GSK3β in the hippocampus. Blocking phosphorylation of GSK3α and GSK3β diminished the anti-immobility effect of fluoxetine treatment in the forced swim test, wherein the effect of GSK3β was more prominent. These results together suggest that PI3K/Akt is a signaling mechanism mediating the GSK3-regulating effect of 5-HT1A receptors in the hippocampus, and regulation of GSK3 is an important intermediate signaling process in the behavioral functions of 5-HT1A receptors and fluoxetine. [Display omitted] ► 5-HT1A receptors regulate phosphorylation of GSK3 in the hippocampus. ► PI3K/Akt signaling pathway mediates regulation of GSK3 by 5-HT1A receptors. ► 5-HT1A receptor-induced inhibition of contextual fear learning is GSK3β-dependent. ► Fluoxetine regulates phosphorylation of GSK3 in the hippocampus. ► Regulation of GSK3 is an intermediate of fluoxetine's anti-immobility effect

Low Cost Test Pattern Generation in Scan-Based BIST Schemes

This paper proposes a low-cost test pattern generator for scan-based built-in self-test (BIST) schemes. Our method generates broadcast-based multiple single input change (BMSIC) vectors to fill more scan chains. The proposed algorithm, BMSIC-TPG, is based on our previous work multiple single-input change (MSIC)-TPG. The broadcast circuit expends MSIC vectors, so that the hardware overhead of the test pattern generation circuit is reduced. Simulation results with ISCAS’89 benchmarks and a comparison with the MSIC-TPG circuit show that the proposed BMSIC-TPG reduces the circuit hardware overhead about 50% with ensuring of low power consumption and high fault coverage