It has been found that the incidence of cardiovascular disease in patients with lower limb amputation is significantly higher than that in normal people, and the risk of developing coronary atherosclerosis is much higher than that in other high-risk groups. Numerous studies have confirmed that high systolic and diastolic blood pressures are potential risk factors for coronary artery disease, and it has been demonstrated that the ascending aortic pressure during diastole increases after amputation. However, the relationship between lower limb amputation and coronary atherosclerosis has not been fully explained from the perspective of hemodynamic environment. Therefore, in this study, a centralized parameter model of the human cardiovascular system and a three-dimensional model of the left coronary artery were established to investigate the effect of amputation on the hemodynamic environment of the coronary artery. The results showed that the abnormal hemodynamic environment induced by amputation, characterized by factors such as increased diastolic pressure in the ascending aorta, led to a significant expansion of the low wall shear stress (WSS) region on the outer lateral aspect of the left coronary artery bifurcation during diastole. The maximum observed increase in the area of low WSS reached up to 50.5%. This abnormal hemodynamic environment elevates the risk of plaque formation in the left coronary artery. Moreover, the more severe the lower limb atrophy, the greater the risk of coronary atherosclerosis in amputees. This study preliminarily reveals the effect of lower limb amputation on the hemodynamic environment of the left coronary artery.
Humans ; Hemodynamics/physiology* ; Amputation, Surgical/adverse effects* ; Coronary Vessels/physiology* ; Coronary Artery Disease/etiology* ; Lower Extremity/surgery* ; Models, Cardiovascular ; Blood Pressure

Objective To analyze the correlation of inflammatory indicators of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),and systemic immune-inflammation index(SII)with traditional Chinese medicine(TCM)syndrome types and Chinese version of Thyroid Imaging Reporting and Data System(C-TIRADS)classification and properties of nodules in the patients with thyroid nodules(TN),thus to provide evidence for guiding TCM syndrome differentiation and treatment,and for assessing C-TIRADS classification and properties of the nodules in patients with TN.Methods A retrospective analysis was carried out in 140 inpatients who were diagnosed as TN and had underwent thyroidectomy during the period of January 2021 to January 2024 in the Department of General Surgery of Guangzhou Integrated Chinese and Western Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine(Guangzhou Hospital of Integrated Traditional and West Medicine).The patients were allocated to various group with reference to TCM syndrome types,C-TIRADS classification,and the properties of TN.The correlation of each clinical indicator with TCM syndrome types and C-TIRADS classification and properties of TN was analyzed.The Spearman correlation coefficient was employed for evaluating the correlation of clinical indicators with the C-TIRADS classification and properties of TN,receiver operating characteristic curve(ROC)was used to analyze the predictive value of NLR,MLR,PLR,and SII for the properties of nodules in patients with TN,and the Youden's Index was used to determine the cutoff value for optimal prediction.Results(1)According to the criteria of TCM syndrome differentiation,72 cases were differentiated as qi stagnation and phlegm obstruction syndrome,65 cases as phlegm accumulation and blood stasis syndrome,and 3 cases as heart-liver yin deficiency syndrome.For the number of cases of heart-liver yin deficiency syndrome was too small,only the first two syndromes were included for the analysis.(2)The levels of free T3(FT3)and free T4(FT4)in the patients of qi stagnation and phlegm obstruction syndrome were higher,and the levels of anti-thyroid peroxidase antibody(A-TPO),anti-thyroglobulin antibody(A-TG),neutrophil(NEU),NLR,and SII were lower than those in the patients of phlegm accumulation and blood stasis syndrome,the differences being all statistically significant(P<0.05 or P<0.01).(3)The levels of NLR,PLR,and SII in the patients with C-TIRADS3 classification were lower than those in the patients with C-TIRADS4 classification,the differences being all statistically significant(P<0.05 or P<0.01);no statistically significant difference of MLR was presented between the patients with C-TIRADS3 classification and those with C-TIRADS4 classification(P>0.05).(4)The levels of NLR,PLR,MLR,and SII in patients with benign nodules were lower than those in patients with malignant nodules,the differences being statistically significant(P<0.05 or P<0.01).(5)The Spearman correlation analysis showed that NLR,PLR,and SII were positively correlated with the C-TIRADS classification of the nodules,and NLR,PLR,MLR,and SII were positively correlated with the properties of the nodules,the differences being all statistically significant(P<0.05 or P<0.01).(6)The levels of NLR,MLR,PLR,and SII in patients with high-risk TN exerted a certain predictive value for the properties of the nodules,and their area under the curve(AUC)was 0.645,0.641,0.604,and 0.716,respectively,the differences being statistically significant(P<0.05 or P<0.01).For the prediction of nodule properties by NLR,MLR,PLR,and SII levels in patients with high-risk TN,their cutoff values and the corresponding sensitivities and specificities were 2.261(0.551,0.791),138.108(0.735,0.527),5.132(0.714,0.495),493.114(0.776,0.615),respectively;and their Youden's Index was 0.342,0.262,0.209,0.391,respectively.Conclusion The results indicated that in patients with TN,the FT3 and FT4 levels are positively correlated with the qi stagnation and phlegm obstruction syndrome;the values of A-TPO,A-TG,NEU,NLR,and SII are positively correlated with the phlegm accumulation and blood stasis syndrome;NLR,PLR and SII values are positively correlated with C-TIRADS classification;NLR,PLR,PLR,SII values are positively correlated with malignant TN.NLR,MLR,PLR,SII values exert high efficiency for the prediction of the properties of nodules in patients with TN.

Objective:To screen and verify the key radioresistance genes regulated by m6A methylation in nasopharyngeal carcinoma (NPC) based on the chip data and cell experiments.Methods:The microarray data of NPC radioresistance genes, m6A regulated genes and mRNA expression profiles of NPC genes were downloaded from Gene Expression Omnibus (GEO) database. The differential genes were screened and statistically analyzed by R software. The biological processes, signal pathways and interaction networks of these genes were analyzed by bioinformatics. The m6A regulatory factors were knocked down and the radioresistant strains were constructed. The above m6A differential radioresistant genes of NPC were screened and verified by real-time reverse transcription PCR (qRT-PCR) and Western blot. The m6A modification of screened genes and their direct binding ability with methyltransferase 3 (METTL3) were verified by methylated RNA immunoprecipitation qPCR (MeRIP-qPCR). The siRNA of selected genes was transfected into NPC cells, and after treatment with ionizing radiation, cell proliferation was detected by CCK-8 assay and EdU, apoptosis and cell cycle were detected by flow cytometry, and radiosensitivity was detected by clone formation assay. The trend of differences in the abundance of Fe 2+ and lipid peroxidation between the control and EGLN3 knockdown groups after ionizing radiation treatment was compared by paired t-test. Results:Chip data GSE48501 intersected with GSE200792 and GSE53819 to obtain 6 differential genes, including EGLN3, FOSL2, ADM, JUN, VEGFA and PRDM1. The target genes of EGLN3 and FOSL2 were further screened by TNMplot and KMplot, etc. The mRNA of the target genes directly bound to METTL3 and were subjected to its mediated modification of m6A. The target genes were up-regulated in the parental cells after irradiation in a dose and time gradient manner, which were also significantly up-regulated in radioresistant cells. After EGLN3 and FOSL2 were down regulated, the proliferation activity of NPC cells was more significantly decreased after irradiation, and the radiosensitization ratio was statistically significant compared with that of NPC cells without EGLN3 and FOSL2 down-regulation. After irradiation, EGLN3 down-regulated NPC cells significantly down-regulated glutathione peroxidase 4 (GPX4) expression, increased the abundance of Fe 2+ and lipid peroxidation, which played a role in radiosensitization by inducing ferroptosis. Conclusions:EGLN3 and FOSL2 play a role in radioresistance in NPC through METTL3 mediated m6A methylation. Down-regulation of EGLN3 combined with ionizing radiation can increase the intracellular Fe 2+ abundance and lipid peroxidation and down-reuglate the expression of GPX4 in NPC cells, which can enhance radiosensitization for NPC radiotherapy by the ferroptosis pathway.

Antimicrobial resistance (AMR), is regarded as one of the top 10 global public health threats. Addressing AMR through the One Health strategy has become a global consensus. AMR monitoring plays a crucial role as the cornerstone of AMR response strategies. This study thoroughly analyzed current situation and progress of AMR monitoring based on the One Health concept in China, the United Kingdom, the United States, and the European Union, and comprehensively compared the similarities and differences of AMR monitoring systems across these countries and regions. The research found that cross-national, cross-regional, and cross-sectoral cooperation in AMR monitoring is increasingly strengthening. However, notable discrepancies still exist among different countries and regions. Notably, most AMR monitoring systems prioritize human and animal health, with relatively insufficient monitoring in the environmental sector. Given the current landscape, China still needs to continue to promote standardized AMR monitoring data sharing and integration across the human, animal, food, and environmental fields, striving to construct a comprehensive and systematic "whole-chain" AMR monitoring system to better tackle this global public health challenge effectively.

Vascular injury resulting from lower limb amputation leads to the redistribution of blood flow and changes in vascular terminal resistance, which can affect the cardiovascular system. However, there was no clear understanding of how different amputation levels affect the cardiovascular system in animal experiments. Therefore, this study established two animal models of above-knee amputation (AKA) and below-knee amputation (BKA) to explore the effects of different amputation levels on the cardiovascular system through blood and histopathological examinations. The results showed that amputation caused pathological changes in the cardiovascular system of animals, including endothelial injury, inflammation, and angiosclerosis. The degree of cardiovascular injury was higher in the AKA group than in the BKA group. This study sheds light on the internal mechanisms of amputation's impact on the cardiovascular system. Based on the amputation level of patients, the findings recommend more comprehensive and targeted monitoring after surgery and necessary interventions to prevent cardiovascular diseases.
Animals ; Animal Experimentation ; Cardiovascular System ; Cardiovascular Diseases ; Hypertension ; Amputation, Surgical

Ferroptosis is a new form of regulated cell death discovered in recent years, which is iron-dependent cell death characterized by peroxidation of polyunsaturated fatty acid phospholipids. Recent studies have shown that radiotherapy can induce ferroptosis in cancer cells via ionizing radiation. Targeting ferroptosis plays a synergistic role in tumor suppression with radiation, which not only further deepens the connotation of radiobiology, but also provides a new perspective for tumor radiosensitization. This review systematically summarizes the occurrence and defense of ferroptosis, focusing on the key role of ferroptosis in the radiobiological effects of tumor cells and the potential application of ferroptosis in radiosensitization.

Objective To investigate the mechanism and the effect of miR-524-5p regulating HEG1 expression on the proliferation and epithelial-mesenchymal transition of esophageal cancer cells. Methods The expression levels of miR-524-5p and HEG1 mRNA in esophageal cancer cells and normal esophageal epithelial cells were detected by qRT-PCR. KYSE30 cells were divided into miR-524-5p mimic group, miR-524-5p NC group, miR-524-5p mimic+pcDNA3.1 group, and miR-524-5p mimic+pcDNA3.1-HEG1 group. Non-transfected cells were set as the normal control group (group Control). CCK-8 method was applied to detect the proliferation ability of KYSE30 cells. Western blot analysis was conducted to detect the expression of proteins related to EMT, invasion, and migration and the HEG1 protein. Scratch and Transwell assays were applied to detect the migration and invasion abilities of KYSE30 cells. A dual-luciferase reporter gene was used to examine the targeting relationship between miR-524-5p and HEG1. Results miR-524-5p was lowly expressed in four esophageal cancer cell lines, namely, TE-1, KYSE30, KYSE150, and NEC (P < 0.05). KYSE30 cells with the lowest expression level were selected for subsequent experiments. HEG1 mRNA was highly expressed in four esophageal cancer cell lines (P < 0.05). The GEPIA database showed that HEG1 was highly expressed in esophageal cancer tumor tissues (P < 0.05). KYSE30 cells in the miR-524-5p mimic group had lower proliferation ability, colony formation number, mesenchymal marker protein expression, and migration and invasion abilities and upregulated epithelial marker protein E-cadherin level than cells in the miR-524-5p NC group (P < 0.05). The miR-524-5p mimic+pcDNA3.1-HEG1 group significantly reversed the inhibitory effect of overexpression of miR-524-5p on the proliferation, epithelial–mesenchymal transformation, invasion, and metastasis of KYSE30 cells (P < 0.05). The luciferase activity of cells in the miR-524-5p mimic and WT-HEG1 co-transfection groups was lower than that in the miR-524-5p NC and WT-HEG1 co-transfection groups (P < 0.05). Conclusion miR-524-5p is lowly expressed in EC cells and tissues. The overexpression of miR-524-5p can negatively regulate the expression of HEG1 in esophageal cancer cell line (KYSE30 cells) and reduce the proliferation, EMT process, and invasion and migration abilities of KYSE30 cells.

【Objective】 To summarize and analyze the clinical data of fumarate hydrase-deficient renal cell carcinoma (FH-RCC), so as to improve the understanding of the disease. 【Methods】 General clinical data of 12 FH-RCC patients treated during Mar.2019 and Dec.2021 were retrospectively analyzed, including the imaging, pathological, genetic testing, surgical and adjuvant therapy, and follow-up results. 【Results】 All cases were confirmed with pathology or genetic tests, including 1 case complicated with uterine fibroids, 3 cases with renal cysts, 4 with family history of uterine fibroids and 2 with family history of renal carcinoma. Cysticular irregular density shadows with an enhancement of 25.8 Hu were detected in 4 cases. Of the 7 cases undergoing genetic testing, 2 had embryo and system mutation, 1 had germ line mutation, 1 had system mutation, and 3 had no germ line or system mutation. Radical nephrotomy was performed in 9 cases. The average operation time was 3.8 h, and the average amount of blood loss was 625 mL. Immunotherapy with targeted therapy was conducted in 10 cases, surgery with postoperative adjuvant therapy in 7 cases, and tyrosine kinase inhibitor with immune checkpoint inhibitor (TKI/ICI) in 1 case. All 12 cases were followed up, 3 died of tumor, 1 had no recurrence, 8 showed progress on imaging. 【Conclusion】 FH-RCC is a rare and highly malignancy prone to metastasis. Imaging shows cystic solid space occupying lesions. FH immunohistochemical staining is negative. Genetic testing is needed to confirm the diagnosis. TKI/ICI combination therapy has a good survival benefit.