OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations, while reliable biomarkers to detect or monitor are still under investigation. Recent advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers, including proteins, ribonucleic acids (RNAs), and deoxyribonucleic acids (DNAs), for early detection of pathological changes in susceptible patients, rapid diagnosis at the bedside after onset, and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.

Objective To discuss the clinical application of coronary CT angiography(CCTA)-derived fractional flow reserve(CT-FFR)in evaluating the risk stratification of the coronary artery stenosis and atherosclerotic plaque quantitative parameters.Methods A total of 122 patients,who received CCTA examination at the Xuzhou Municipal Central Hospital of China,were enrolled in this study.The patients were divided into non-ischemia group(CT-FFR＞0.8,n=66)and ischemia group(CT-FFR0.8,n=56).The characteristics of atherosclerotic plaque were compared between the two groups.Logistic regression analysis was used to analyze the correlation between plaque characteristics and ischemic lesions.Results There were 218 vessels having a CT-FFR＞0.8 and 174 vessels having a CT-FFR ≤0.8.Statistically significant differences in the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％existed between the two groups(all P＜0.05).Logistic regression analysis indicated that the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％were the risk factors for myocardial ischemia.Conclusion CT-FFR can be used for the risk stratification of coronary stenosis and atherosclerotic plaque characteristics,which can evaluate the local myocardial blood supply condition from the anatomical stenosis and functional level so as to optimize the diagnosis and treatment measures.

The theory of yin and yang is the modest differentiation thought of the traditional Chinese medicine under the guidance of overall dialectics,and the dynamic changes of yin and yang profit and loss can reflect the life activities of the human body.In the early literature research and clinical practice,the author's team found that the"yang deficiency and yin stagnation"is the key pathogen of colorectal cancer,the yang qi is insufficient,and the metabolites of the yin such as phlegm,wetness and stasis are lost in gasification and accumulate to form a"yin tumor",which is stagnant in the intestine and forms colorectal cancer.Yang Qi is the process of normal cell metabolism to produce energy,Yang Qi is insufficient,the"yin knot"of the thing in the body polymerizes into tumors,The imbalance of yin and yang can cause changes in energy or substance metabolism in the body,and glutamine is one of the amino acid which is the largest consumption of tumor cells,and its metabolic process not only provides a material basis for tumor cell growth,but also creates an acidic microenvironment of hypoxia to promote the proliferation and growth of tumor cells.This paper discusses the characteristics of glutamine metabolism of colorectal cancer cells in detail,aiming to explain the occurrence of colorectal cancer from the pathogenesis of"yang deficiency yin knot",and to explain the scientific theory of traditional Chinese medicine in the treatment of coloral cancer with the principle of Wenyang Tongxia,aiming to provide new ideas and methods for the comprehensive treatment of CRC.

Experimental animal models are an essential part of basic research on colorectal cancer.It is important for basic research on colorectal tumor treatment in TCM to construct animal models with the characteristics of TCM based on the theory of TCM diagnosis and treatment,so that the animal models can meet the characteristics of both western medicine and TCM symptoms.In this paper,we summarize the methods and characteristics of animal models of colorectal tumors and the combination of disease and evidence for scientific research on colorectal tumors through literature review,in order to provide reference for researchers engaged in scientific research on colorectal tumors.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Dysregulated crosstalk between different signaling pathways contributes to tumor development, including resistance to cancer therapy. In the present study, we found that the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib failed to suppress the proliferation of PANC-1 and MGC803 cells by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, while the JAK2 inhibitor fedratinib failed to inhibit the growth of the PANC-1 cells upon stimulation of extracellular signal-regulated kinase (ERK) signaling. In particular, the most prominent enhancement of the anti-proliferative effect resulted from the concurrent blockage of the JAK2/STAT3 and ERK signaling pathways. Furthermore, the combination of the two inhibitors resulted in a reduced tumor burden in mice. Our evidence suggests novel crosstalk between JAK2/STAT3 and ERK signaling in gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC) cells and provides a therapeutic strategy to overcome potential resistance in gastrointestinal cancer.

Birth defects and rare diseases have become major public health problems, and early prevention and control are the most effective interventions. In recent years, with the rapid development of genomic techniques such as high-throughput sequencing, the level of screening and diagnosis of genetic birth defects and rare diseases has been greatly improved. This article reviews the application of genomic technologies in the pre-pregnancy, preimplantation, prenatal and neonatal stages, as well as the trend of clinical transformation, highlighting the broad prospects of constructing an early and precise prevention and control system in the era of genomic medicine.

Birth defects and rare diseases have become major public health problems, and early prevention and control are the most effective interventions. In recent years, with the rapid development of genomic techniques such as high-throughput sequencing, the level of screening and diagnosis of genetic birth defects and rare diseases has been greatly improved. This article reviews the application of genomic technologies in the pre-pregnancy, preimplantation, prenatal and neonatal stages, as well as the trend of clinical transformation, highlighting the broad prospects of constructing an early and precise prevention and control system in the era of genomic medicine.