An Exploratory Pilot Study on the Application of Radiofrequency Ablation for Atrial Fibrillation Guided by Computed Tomography-Based 3D Printing Technology.

Radiofrequency ablation (RFA) is the treatment of choice for atrial fibrillation (AF). Additionally, the utilization of 3D printing for cardiac models offers an in-depth insight into cardiac anatomy and cardiovascular diseases. The study aims to evaluate the clinical utility and outcomes of RFA following in vitro visualization of the left atrium (LA) and pulmonary vein (PV) structures via 3D printing (3DP). Between November 2017 and April 2021, patients who underwent RFA at the First Affiliated Hospital of Xinxiang Medical University were consecutively enrolled and randomly allocated into two groups: the 3DP group and the control group, in a 1:1 ratio. Computed tomography angiography (CTA) was employed to capture the morphology and diameter of the LA and PV, which facilitated the construction of a 3D entity model. Additionally, surgical procedures were simulated using the 3D model. Parameters such as the duration of the procedure, complications, and rates of RFA recurrence were meticulously documented. Statistical analysis was performed using the t-test or Mann-Whitney U test to evaluate the differences between the groups, with a P-value of less than 0.05 considered statistically significant. In this study, a total of 122 patients were included, with 53 allocated to the 3DP group and 69 to the control group. The analysis of the morphological measurements of the LA and PV taken from the workstation or direct entity measurement showed no significant difference between the two groups (P > 0.05). However, patients in the 3DP group experienced significantly shorter RFA times (97.03 ± 28.39 compared to 120.51 ± 44.76 min, t = 3.05, P = 0.003), reduced duration of radiation exposure (2.55 [interquartile range 2.01, 3.24] versus 3.20 [2.28, 3.91] min, Z = 3.23, P < 0.001), and shorter modeling times (7.68 ± 1.03 compared to 8.89 ± 1.45 min, t = 5.38, P < 0.001). 3DP technology has the potential to enhance standard RFA practices by reducing the time required for intraoperative interventions and exposure to radiation.

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism".

Introduction: Hypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways. Materials and methods: In Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed. Results: In Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005-0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172-0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046-0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029-0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004-0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002-0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676-0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644-0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123-3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953-2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms. Conclusion: Defluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism" and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.

Characterization of the novel HLA-DRB1*16:76 allele in a Chinese individual.

The HLA-DRB1*16:76 allele differs from HLA-DRB1*16:02:01 by one nucleotide substitution (A > G) at position 37 in exon 1.

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment.

Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/ .

Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy.

The advent of single-cell RNA sequencing (scRNA-seq) has provided insight into the tumour immune microenvironment (TIME). This review focuses on the application of scRNA-seq in investigation of the TIME. Over time, scRNA-seq methods have evolved, and components of the TIME have been deciphered with high resolution. In this review, we first introduced the principle of scRNA-seq and compared different sequencing approaches. Novel cell types in the TIME, a continuous transitional state, and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer. Thus, we concluded novel cell clusters of cancer-associated fibroblasts (CAFs), T cells, tumour-associated macrophages (TAMs) and dendritic cells (DCs) discovered after the application of scRNA-seq in TIME. We also proposed the development of TAMs and exhausted T cells, as well as the possible targets to interrupt the process. In addition, the therapeutic interventions based on cellular interactions in TIME were also summarized. For decades, quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer. Summarizing the current findings, we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy, which can subsequently be implemented in the clinic. Finally, we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

SIRT6 in Vascular Diseases, from Bench to Bedside.

Aging is a key risk factor for angiogenic dysfunction and cardiovascular diseases, including heart failure, hypertension, atherosclerosis, diabetes, and stroke. Members of the NAD+-dependent class III histone deacetylase family, sirtuins, are conserved regulators of aging and cardiovascular and cerebrovascular diseases. The sirtuin SIRT6 is predominantly located in the nucleus and shows deacetylase activity for acetylated histone 3 lysine 56 and lysine 9 as well as for some non-histone proteins. Over the past decade, experimental analyses in rodents and non-human primates have demonstrated the critical role of SIRT6 in extending lifespan. Recent studies highlighted the pleiotropic protective actions of SIRT6 in angiogenesis and cardiovascular diseases, including atherosclerosis, hypertension, heart failure, and stroke. Mechanistically, SIRT6 participates in vascular diseases via epigenetic regulation of endothelial cells, vascular smooth muscle cells, and immune cells. Importantly, SIRT6 activators (e.g., MDL-800/MDL-811) have provided therapeutic value for treating age-related vascular disorders. Here, we summarized the roles of sirtuins in cardiovascular diseases; reviewed recent advances in the understanding of SIRT6 in vascular biology, cardiovascular aging, and diseases; highlighted its therapeutic potential; and discussed future perspectives.

Metabolic regulation of immune cells in proinflammatory microenvironments and diseases during ageing.

The process of ageing includes molecular changes within cells and interactions between cells, eventually resulting in age-related diseases. Although various cells (immune cells, parenchymal cells, fibroblasts and endothelial cells) in tissues secrete proinflammatory signals in age-related diseases, immune cells are the major contributors to inflammation. Many studies have emphasized the role of metabolic dysregulation in parenchymal cells in age-related inflammatory diseases. However, few studies have discussed metabolic modifications in immune cells during ageing. In this review, we introduce the metabolic dysregulation of major nutrients (glucose, lipids, and amino acids) within immune cells during ageing, which leads to dysfunctional NAD + metabolism that increases immune cell senescence and leads to the acquisition of the corresponding senescence-associated secretory phenotype (SASP). We then focus on senescent immune cell interactions with parenchymal cells and the extracellular matrix and their involvement in angiogenesis, which lead to proinflammatory microenvironments in tissues and inflammatory diseases at the systemic level. Elucidating the roles of metabolic modifications in immune cells during ageing will provide new insights into the mechanisms of ageing and therapeutic directions for age-related inflammatory diseases.

Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments.

Cardiovascular diseases have become the leading cause of human death. Aging is an independent risk factor for cardiovascular diseases. Cardiac aging is associated with maladaptation of cellular metabolism, dysfunction (or senescence) of cardiomyocytes, a decrease in angiogenesis, and an increase in tissue scarring (fibrosis). These events eventually lead to cardiac remodeling and failure. Senescent cardiomyocytes show the hallmarks of DNA damage, endoplasmic reticulum stress, mitochondria dysfunction, contractile dysfunction, hypertrophic growth, and senescence-associated secreting phenotype (SASP). Metabolism within cardiomyocytes is essential not only to fuel the pump function of the heart but also to maintain the functional homeostasis and participate in the senescence of cardiomyocytes. The senescence of cardiomyocyte is also regulated by the non-myocytes (endothelial cells, fibroblasts, and immune cells) in the local microenvironment. On the other hand, the senescent cardiomyocytes alter their phenotypes and subsequently affect the non-myocytes in the local microenvironment and contribute to cardiac aging and pathological remodeling. In this review, we first summarized the hallmarks of the senescence of cardiomyocytes. Then, we discussed the metabolic switch within senescent cardiomyocytes and provided a discussion of the cellular communications between dysfunctional cardiomyocytes and non-myocytes in the local microenvironment. We also addressed the functions of metabolic regulators within non-myocytes in modulating myocardial microenvironment. Finally, we pointed out some interesting and important questions that are needed to be addressed by further studies.

Effects of Radix Puerariae flavones on liver lipid metabolism in ovariectomized rats.

AIM: To study the effects of Radix Puerariae flavones (RPF) on liver lipid metabolism in ovariectomized (OVX) rats. METHODS: Forty adult female Wistar rats were randomly divided into four groups: OVX group; sham-OVX group; OVX+estrogen group and OVX+RPF group. One week after operation rats of the first two groups were treated with physiological saline, rats of OVX+estrogen group with estrogen (1 mg/kg.b.w.) and rats of OVX+RPF group with RPF (100 mg/kg.b.w.), respectively for 5 weeks. After the rats were killed, their body weight, the weight of the abdominal fat and uterus were measured, and the levels of total cholesterol (TC) and triglyceride (TG) in liver homogenate were determined. RESULTS: Compared with the sham-OVX group, the body mass of the rats in OVX group was found increased significantly; more abdominal fat in store; TC and TG in liver increased and uterine became further atrophy. As a result, the RPF was found to have an inhibitive action on those changes of various degrees. CONCLUSION: RPF has estrogen-like effect on lipid metabolism in liver and adipose tissue.

[Effect of chailing decoction and its active ingredients on experimental nephritis in rats].

OBJECTIVE: To screen the active ingredients of Chailing decoction (CLD) by using rat nephritis model induced by mono-colonal antibody 1-22-3 (mAb) injection. METHODS: The active ingredients of CLD was screened by 5 successive times of experiment. In each time, 28 rats were randomly divided into 4 groups, 7 in each. Group 1 was treated with PBS as control, Groups 2-4 were treated separately with CLD and its various ingredients, the medication was started 5 days before and lasted to 8 days after modeling by peritoneal injection, 13 days totally. All the rats were killed 8 days after modeling to observe the effect of various drugs on proteinuria, morphological change of kidney and biochemical parameters. RESULTS: CLD, Xiaochaihu decoction, various combination of thorowax root and its extract (saikosaponin-d) could reduce urinary protein, inhibit the proliferation of mesangial cell and expansion of extracellular matrix. CONCLUSION: CLD and its active ingredients had inhibition on mAb induced rat model of nephritis, the active is saikosaponin-d.