Clinical and translational discovery最新文献

The high risk of patients with chronic lung diseases in developing into lung cancer has been recognised, but the key factors driving such procedure are still barely known. Dendritic cells (DCs) as major antigen presenting cells take part in the immune response in the very upstream, and myeloid DCs regulate the inflammation in pulmonary diseases. In this article, we performed single-cell RNA sequencing (scRNA-seq) analyses on DCs from pulmonary diseases. We explore the DC characteristics in chronic lung diseases, lung cancer and healthy control samples. We discover that a special type of DC, which is highly associated with inflammatory, inf-DC, is abundant in lung cancer samples. Furthermore, we find that there are about 10% patients with chronic lung diseases also has such inf-DC-rich pattern. Such proportion is consistent to the fact that about 10% chronic lung disease patients finally developed into cancer. Our findings indicate inf-DC could be a potential factor to predict the risk of chronic lung disease developing into cancer.

Diabetes mellitus (DM) has become a major chronic disease seriously affecting human health. Type 2 diabetes mellitus (T2DM) accounts for about 90% of DM patients, which is the largest type. Approximately 25–35% of T2DM patients develop kidney disease, which not only impacts the survival rate and quality of life but also, to the family and society, are of great economic burden. Early identification of high-risk T2DM patients with kidney disease is crucial for initiating targeted prevention and treatment measures in time to reduce or delay the occurrence and progression of diabetic kidney disease. Previous studies have identified a variety of clinical predictors for the progression of renal function in T2DM patients, including proteinuria, estimated glomerular filtration rate, blood glucose, blood pressure, serum uric acid, dyslipidemia, obesity, smoking, duration of DM, age, gender, race, family history of DM, and diabetic retinopathy. Clinical prediction models based on conventional clinical indicators are instrumental in evaluating the risk of kidney disease in T2DM patients, assisting in patient risk stratification. This article systematically reviews the clinical prediction factors and prediction models associated with the progression of renal function in T2DM patients, providing a comprehensive and current reference for improved clinical assessment of the risk of renal function progression.

With rapid development and mature of single-cell measurements, single-cell biology and pathology become an emerging discipline to understand the disease. However, it is important to address concerns raised by clinicians as to how to apply single-cell measurements for clinical practice, translate the signals of single-cell systems biology into determination of clinical phenotype, and predict patient response to therapies. The present Perspective proposes a new system coined as the clinical artificial intelligent single-cell (caiSC) with the dynamic generator of clinical single-cell informatics, artificial intelligent analysers, molecular multimodal reference boxes, clinical inputs and outs, and AI-based computerization. This system provides reliable and rapid information for impacting clinical diagnoses, monitoring, and prediction of the disease at the single-cell level. The caiSC represents an important step and milestone to translate the single-cell measurement into clinical application, assit clinicians’ decision-making, and improve the quality of medical services. There is increasing evidence to support the possibility of the caiSC proposal, since the corresponding biotechnologies associated with caiSCs are rapidly developed. Therefore, we call the special attention and efforts from various scientists and clinicians on the caiSCs and believe that the appearance of the caiSCs can shed light on the future of clinical molecular medicine.

Recent research has highlighted the significant effects of high-fat diets (HFDs) on brain health, particularly focusing on mitochondrial complex I activity and protein lipoxidation. Mitochondrial complex I, the first enzyme of the electron transport chain, is crucial for oxidative phosphorylation and adenosine triphosphate (ATP) production. In individuals consuming an HFD, complex I activity notably increases, initially appearing beneficial due to enhanced energy production. However, this upregulation is linked to elevated reactive oxygen species (ROS) production, leading to oxidative stress and mitochondrial dysfunction. Over the past 5 years, studies have associated this imbalance with neurodegenerative conditions and cognitive decline in obese individuals.¹

The brain's energy demands are met primarily through oxidative phosphorylation, with mitochondrial complex I playing a pivotal role. In the context of an HFD, complex I activity is upregulated, ostensibly to meet increased energy requirements. However, this heightened activity has a significant downside. Increased complex I activity is closely associated with ROS production, chemically reactive molecules containing oxygen. While ROS are normal byproducts of cellular metabolism, excessive ROS production can overwhelm the cell's antioxidant defences, leading to oxidative stress (Figure 1).^{2, 3}

Oxidative stress is a critical factor in the pathogenesis of neurodegenerative diseases. It damages cellular components, including lipids, proteins and DNA, disrupting normal cellular functions and leading to cell death. In the brain, which has a high metabolic rate and limited regenerative capacity, oxidative stress is particularly detrimental. Studies have shown that in obese individuals, the brain exhibits higher levels of oxidative damage, correlated with cognitive impairments and increased risk of neurodegenerative disorders such as Alzheimer's disease. Lipoxidation, the oxidative modification of proteins by lipid peroxidation products, is another significant consequence of a HFD. Lipid peroxidation is a process where ROS attack polyunsaturated fatty acids in cell membranes, resulting in the formation of reactive lipid aldehydes. These aldehydes can covalently modify proteins, forming advanced lipoxidation end-products (ALEs). ALEs accumulate in neural tissues and alter protein structure and function, leading to impaired cellular processes and neuronal damage.^{4, 5}

The brain's synaptic function is particularly vulnerable to lipoxidation. Synaptic proteins are essential for neurotransmission, and their modification by ALEs can disrupt signal transduction, leading to synaptic dysfunction, cognitive deficits and neurodegenerative changes. Recent studies have provided evidence that the increased ROS production due to elevated complex I activity accelerates lipid peroxidation, thereby enhancing protein lipoxidati

Financial interactions between pharmaceutical companies and physicians introduce conflicts of interest among physicians, and can unduly influence physicians' clinical decision-making, such as increased use of non-recommended cancer treatments and higher healthcare expenditures. Breast cancer is the most common cancer for which there is a growing number of novel treatments. Nevertheless, the financial relationships between pharmaceutical companies and physicians treating patients with breast cancer remain unknown. Using payment data disclosed by major pharmaceutical companies in Japan between 2016 and 2020, this study examined size and trends in non-research payments from the pharmaceutical companies to breast cancer specialists who were board-certified by the Japanese Breast Cancer Society. A total of $17.2 million were made to 1349 or 77.8% of all board-certified breast cancer specialists over the five years. Of all specialists, 41.9% to 55.5% received the payments each year. The median payments per specialist were $1,149–$1,371 annually. Only 5op 1% and 10% of all specialists received 24.7% and 70.3% of all payments to the specialists. The payments per specialist significantly increased by 9.9% (95% confidence interval: 6.713.1, p < 0.001) from 2016 to 2019, but decreased by 29.6% (95% CI: −34.4 to −24.5, p < 0.001) in 2020 when the COVID-19 pandemic occurred. Given that even a small payment to physicians is associated with their clinical practice, it is imperative that these breast cancer specialists are more aware of the potential influence of payments on their decision-making.