Exploring the therapeutic potential of garlic in alcoholic liver disease: a network pharmacology and experimental validation study.

OBJECTIVE: Employing network pharmacology and molecular docking, the study predicts the active compounds in garlic and elucidates their mechanism in inhibiting the development of alcoholic liver disease (ALD). ALD is a global chronic liver disease with potential for hepatocellular carcinoma progression. METHODS: The main active ingredients and targets of garlic were identified through screening the TCMSP, TCM-ID, and ETCM databases. ALD disease targets were sourced from DisGeNET, GeneCards, and DiGSeE databases, and intervention targets for garlic were determined through intersections. Protein interaction networks were constructed using the STRING platform, and GO and KEGG pathway enrichment analyses were performed with R software. The garlic component-disease-target network was established using Cytoscape software. Validation of active ingredients against core targets was conducted through molecular docking simulations using AutoDock Vina software. Expression validation of core targets was carried out using human sequencing data of ALD obtained from the GEO database. RESULTS: Integration of garlic drug targets with ALD disease targets identified 83 target genes. Validation through an alcohol-induced ALD mouse model supported certain network pharmacology findings, suggesting that garlic may impede disease progression by mitigating the inflammatory response and promoting ethanol metabolism. CONCLUSION: This study provides insights into the potential therapeutic mechanisms of garlic in inhibiting ALD development. The identified active ingredients offer promising avenues for further investigation and development of treatments for ALD, emphasizing the importance of botanical remedies in liver disease management.

High estrogen induces trans-differentiation of vascular smooth muscle cells to a macrophage-like phenotype resulting in aortic inflammation via inhibiting VHL/HIF1a/KLF4 axis.

Estrogen is thought to have a role in slowing down aging and protecting cardiovascular and cognitive function. However, high doses of estrogen are still positively associated with autoimmune diseases and tumors with systemic inflammation. First, we administered exogenous estrogen to female mice for three consecutive months and found that the aorta of mice on estrogen develops inflammatory manifestations similar to Takayasu arteritis (TAK). Then, in vitro estrogen intervention was performed on mouse aortic vascular smooth muscle cells (MOVAS cells). Stimulated by high concentrations of estradiol, MOVAS cells showed decreased expression of contractile phenotypic markers and increased expression of macrophage-like phenotypic markers. This shift was blocked by tamoxifen and Krüppel-like factor 4 (KLF4) inhibitors and enhanced by Von Hippel-Lindau (VHL)/hypoxia-inducible factor-1α (HIF-1α) interaction inhibitors. It suggests that estrogen-targeted regulation of the VHL/HIF-1α/KLF4 axis induces phenotypic transformation of vascular smooth muscle cells (VSMC). In addition, estrogen-regulated phenotypic conversion of VSMC to macrophages is a key mechanism of estrogen-induced vascular inflammation, which justifies the risk of clinical use of estrogen replacement therapy.

Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation.

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.

The Down-Shifting Luminescence of Rare-Earth Nanoparticles for Multimodal Imaging and Photothermal Therapy of Breast Cancer.

Nanotheranostic agents capable of simultaneously enabling real-time tracking and precise treatment at tumor sites play an increasingly pivotal role in the field of medicine. In this article, we report a novel near-infrared-II window (NIR-II) emitting downconversion rare-earth nanoparticles (RENPs) to improve image-guided therapy for breast cancer. The developed α-NaErF4@NaYF4 nanoparticles (α-Er NPs) have a diameter of approximately 24.1 nm and exhibit superior biocompatibility and negligible toxicity. RENPs exhibit superior imaging quality and photothermal conversion efficiency in the NIR-II range compared to clinically approved indocyanine green (ICG). Under 808 nm laser irradiation, the α-Er NPs achieve significant tumor imaging performance and photothermal effects in vivo in a mouse model of breast cancer. Simultaneously, it combines X-ray computed tomography (CT) and ultrasound (US) tri-modal imaging to guide therapy for cancer. The integration of NIR-II imaging technology and RENPs establishes a promising foundation for future medical applications.

Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

BACKGROUND: Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. METHODS: This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. RESULTS: (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. CONCLUSIONS: Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

Understanding the role of red blood cells in venous thromboembolism: A comprehensive review.

Traditionally, red blood cells (RBCs) have been perceived as passive entities within the fibrin network, without any significant role in the pathophysiology of venous thromboembolism (VTE). This review explores the involvement of RBCs in the VTE process, summarizing previous study findings and providing a comprehensive review of the latest theories. At first, it explores the influence of abnormal RBC counts (as seen in polycythemia vera and with erythropoietin use) and the exposure of RBCs to phosphatidylserine (Ptd-L-Ser) in the pathophysiology of VTE. The mechanisms of endothelial injury induced by RBCs and their adhesion to the endothelium under different disease models are then demonstrated. We explore the role of physical and chemical interactions between RBCs and platelets, as well as the interactions between RBCs and neutrophils - particularly the neutrophil extracellular traps (NETs) released by neutrophils - in the process of VTE. Additionally, we investigate the effect of RBCs on thrombin activation through two pathways, namely, the FXIIa-FXI-FIX pathway and the prekallikrein-dependent pathway. Lastly, we discuss the impact of RBCs on clot volume. In conclusion, we propose several potential methods aimed at unraveling the role of RBCs and their interaction with other components in the vascular system in the pathogenesis of VTE.

Fluoroquinolones increase susceptibility to aortic aneurysm and aortic dissection: Molecular mechanism and clinical evidence.

Aortic aneurysm (AA) and aortic dissection (AD) are prevalent severe cardiovascular diseases that result in catastrophic complications and unexpected deaths. Owing to the lack of clinically established and effective medications, the only treatment options are open surgical repair or endovascular therapy. Most researchers have focused on the development of innovative medications or therapeutic targets to slow the progression of AA/AD or lower the risk of malignant consequences. Recent studies have shown that the use of fluoroquinolones (FQs) may increase susceptibility to AA/AD to some extent, especially in patients with aortic dilatation and those at a high risk of AD. Therefore, it is crucial for doctors, particularly those in cardiovascular specialties, to recognize the dangers of FQs and adopt alternatives. In the present review, the main clinical observational studies on the correlation between FQs and AA/AD in recent years are summarized, with an emphasis on the relative physiopathological mechanism incorporating destruction of the extracellular matrix (ECM), phenotypic transformation of vascular smooth muscle cells, and local inflammation. Although additional data are required, it is anticipated that the rational use of FQs will become the standard of care for the treatment of aortic diseases.

Transcatheter arterial chemoembolization plus apatinib with or without camrelizumab for unresectable hepatocellular carcinoma: a multicenter retrospective cohort study.

BACKGROUND: The evidence of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitor and immune checkpoint inhibitor in unresectable hepatocellular carcinoma (HCC) was limited. This study aimed to evaluate the role of TACE plus apatinib (TACE + A) and TACE combined with apatinib plus camrelizumab (TACE + AC) in patients with unresectable HCC. METHODS: This study retrospectively reviewed patients with unresectable HCC who received TACE + A or TACE + AC in 20 centers of China from January 1, 2019 to June 31, 2021. Propensity score matching (PSM) at 1:1 was performed to reduce bias. Treatment-related adverse events (TRAEs), overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were collected. RESULTS: A total of 960 eligible patients with HCC were included in the final analysis. After PSM, there were 449 patients in each group, and the baseline characteristics were balanced between two groups. At data cutoff, the median follow-up time was 16.3 (range: 11.9-21.4) months. After PSM, the TACE + AC group showed longer median OS (24.5 vs 18.0 months, p < 0.001) and PFS (10.8 vs 7.7 months, p < 0.001) than the TACE + A group; the ORR (49.9% vs 42.5%, p = 0.002) and DCR (88.4% vs 84.0%, p = 0.003) of the TACE + AC group were also higher than those in the TACE + A group. Fever, pain, hypertension and hand-foot syndrome were the more common TRAEs in two groups. CONCLUSIONS: Both TACE plus apatinib and TACE combined with apatinib plus camrelizumab were feasible in patients with unresectable HCC, with manageable safety profiles. Moreover, TACE combined with apatinib plus camrelizumab showed additional benefit.

Safety and Efficacy of the Passeo-18 Lux Drug-Coated Balloon Catheter in Atherosclerotic Femoropopliteal Lesions: The Multicenter BIOLUX P-IV China Study.

BACKGROUND: The purpose of this trial was to assess the safety and effectiveness of a paclitaxel-coated balloon catheter in Chinese patients with de novo or nonstented restenotic femoropopliteal atherosclerotic lesions. METHODS: BIOLUX P-IV China is a prospective, independently adjudicated, multicenter, single-arm trial conducted in China. Patients with Rutherford class 2-4 were eligible, excluded were patients in which predilation resulted in severe (≥ grade D) flow-limiting dissection or residual stenosis > 70%. Follow-up assessments were conducted at 1, 6, and 12 months. The primary safety end point was 30-day major adverse event rate and the primary effectiveness end point was primary patency at 12 months. RESULTS: We enrolled 158 patients with 158 lesions. Mean age was 67.6 ± 9.6 years, diabetes was present in 53.8% (n = 85), and previous peripheral intervention/surgeries in 17.1% (n = 27). Lesions were 4.1 ± 0.9 mm in diameter and 74 ± 50 mm long with a mean diameter stenosis of 91 ± 13%; 58.2% (n = 92) were occluded (core laboratory analysis). Device success was achieved in all patients. The rate of major adverse events was 0.6% (95% confidence interval: 0.0; 3.5) at 30 days, consisting of 1 target lesion revascularization. At 12 months, binary restenosis was present in 18.7% (n = 26) and target lesion revascularization was performed in 1.4% (n = 2, all clinically driven), resulting in a primary patency of 80.0% (95% confidence interval: 72.4, 85.8); no major target limb amputation occurred. Clinical improvement at 12 months, defined as improvement of at least 1 Rutherford class, was 95.3% (n = 130). The median walking distance per 6-minute walk test was 279 m at baseline and improved by 50 m at 30 days and by 60 m at 12 months; the visual analogue scale changed from 76.6 ± 15.6 at baseline to 80.0 ± 15.0 at 30 days and 78.6 ± 14.6 at 12 months. CONCLUSIONS: Our results confirmed the clinical effectiveness and safety of a paclitaxel-coated peripheral balloon dilatation catheter for the treatment of de novo and nonstented restenotic lesion of the superficial femoral and proximal popliteal artery in Chinese patients (NCT02912715).

Influence of vitamin D supplementation on immune function of healthy aging people: A pilot randomized controlled trial.

Objectives: This study aims to investigate the influence of vitamin D supplementation on immune function of healthy older adults. Materials and methods: Designed as a randomized controlled trial, 21 participants (55-85 years) completed the study during May-November 2018 in Coventry, England. The participants were randomized into vitamin D or the control group, stratified by age, gender and body mass index. The vitamin D group (n = 12) took vitamin D3 tablets of 1,000 IU/day for 12 weeks plus vitamin D education leaflet, while the control group (n = 9) were only provided with the leaflet. At baseline, 6 and 12 weeks, plasma 25(OH)D levels and immunological and metabolic parameters including phagocytic activity of granulocytes and monocytes, tumor necrosis factor, interleukin 6, lymphocyte subsets and fasting blood glucose and lipid were measured. Dietary vitamin D intake was analyzed at baseline and week 12. Data were presented as mean ± SD. Two-way repeated measures ANOVA and independent t-test were used to analyze the data. Results: At baseline, 42.9% of the participants were vitamin D deficiency (25(OH)D < 25 nmol/L), only 10% achieved a level of 25(OH)D > 50 nmol/L. Overweight/obese participants (n = 9) had significantly lower mean plasma 25(OH)D concentration (22.3 ± 8.7 nmol/L) than normal weight participants (48.1 ± 34.3 nmol/L) (P = 0.043). There was a significant increase in plasma 25(OH)D concentration in vitamin D group compared with that in control group (P = 0.002) during the intervention period. The plasma 25(OH)D concentration in vitamin D group was increased at 6 weeks (from 38.4 ± 37.0 nmol/L at baseline to 51.0 ± 38.2 nmol/L) with little change observed between 6 and 12 weeks (51.8 ± 36.4 nmol/L). The plasma creatinine concentration in vitamin D group was significantly decreased compared with the control group (P = 0.036) (79.8 ± 7.0 µmol/L at baseline vs 75.1 ± 5.4 µmol/L at week 12). No significant effect of vitamin D supplementation was determined on immunological parameters. Conclusion: Vitamin D deficiency is common among the aging population in the UK even during the summertime. Vitamin D supplementation at 1,000 IU/day for 12 weeks significantly increased plasma 25(OH)D concentration but showed no effect on metabolic and immunological parameters except decreased plasma creatinine.

Novel Diagnostic Biomarkers Related to Oxidative Stress and Macrophage Ferroptosis in Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease, which has a complex interplay between altered immune metabolism and oxidative stress. Therefore, we aimed to determine the oxidative stress and immune-related biomarkers in AS. Differential gene expression analyses are based on the GSE100927 dataset in the Gene Expression Omnibus (GEO), and 389 oxidative stress (OS) genes are identified based on gene set enrichment analysis (GSEA). We identified 74 differentially expressed genes related to oxidative stress (DEOSGs). "CIBERSORT" and "WGCNA" R Packages were used to compare the differences in immune infiltration levels between AS and control samples. The DEOSGs (N = 74) were intersected with the key module's genes of WGCNA (N = 972), and 27 differentially expressed immune-related oxidative stress genes (DEIOSGs) were obtained. To identify the pivotal genes, a protein-protein interaction (PPI) network was constructed using the STRING database and the Cytoscape software. MMP9, ALOX5, NCF2, NCF, and NCF4 were identified as diagnostic markers of AS, and we validated them in the GSE57691 dataset. The expression levels of the five diagnostic genes were significantly highly expressed in the AS group. Correlation analysis and single-cell analysis revealed that five diagnostic genes were mainly correlated with macrophages M1. We, respectively, intersected differentially expressed genes (DEGs) with ferroptosis gene set, necroptosis gene set, and pyroptosis gene set. The findings suggested that ALOX5 and NCF2 were differentially expressed genes of ferroptosis. High expression of five hub genes in RAW264.7 macrophages were confirmed by PCR. High ALOX5 and NCF2 expression levels in plaque tissues were confirmed by immunohistochemistry (IHC) and western blotting. Our study identified that MMP9, ALOX5, NCF2, NCF1, and NCF4 were diagnostic genes of AS and associated with oxidative stress. ALOX5 and NCF2 may be involved in the formation of the necrotic core in AS by regulating macrophage ferroptosis.

Prediction of Necroptosis-Related Markers in Head and Neck Carcinoma by Bioinformatics.

Necroptosis is a form of programmed cell death that has recently been shown to be important in the progression of head and neck cancer (HNC). Noncoding RNAs (ncRNAs) are known to function in cell death and tumor formation. In this study, we focused on microRNAs (miRNA) that play roles in necroptosis and the progression of HNC. We collected miRNA expression data, related clinical data of patients with HNC, and miRNA data related to necroptosis. A prognostic multimiRNA molecular marker was generated based on differential expression analysis and univariate and multivariate Cox regression analyses. Target genes of the prognosis-related miRNAs were identified, and their functions were evaluated by Gene Ontology Enrichment Analysis to reveal the processes the miRNAs may be involved in. Eight potentially prognostic miRNAs were identified through differential expression analysis: miR-331-3p, miR-181d-5p, miR-181b-5p, miR-500a-3p, miR-425-5p, miR-181a-5p, miR-141-3p, and miR-200a-5p. Multivariate Cox regression identified the risk score as an independent prognostic factor (univariate Cox regression results: hazard ratio (HR): 2.2028, 95% confidence interval (CI): 1.2640-3.8388, P = 0.0053; multivariate Cox regression results: HR: 2.4168, 95% CI: 1.3743-4.2501, P = 0.0022). Survival curve analysis revealed that patients with a high risk score had a bad prognosis (P = 0.0109). A receiver operating characteristic curve showed that the model has a certain prediction ability. We identified 187 miRNA-related genes, which were enriched in "cell cycle" and "cellular senescence." In conclusion, this study identified eight novel miRNA markers for predicting the prognosis of patients with HNC and paved the way for future research on necroptosis-related genes.

A Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Breast Cancer Metastasis.

Objective: Necroptosis was recently identified as a form of programmed cell death that plays an essential role in breast cancer metastasis. MicroRNAs (miRNAs) have long been recognized to affect cell death and tumor growth. In this study, we aimed to screen for necroptosis-associated miRNAs that predict breast cancer metastasis. Method: This study used The Cancer Genome Atlas (TCGA) public database to obtain miRNA expression data and associated clinical data from breast cancer patients and then retrieved miRNA data related to necrosis and apoptosis. Next, using Cox regression model analysis (univariate or multivariate) as well as a comparison analysis (differential analysis), a prognostic multi-miRNA molecular marker was established. Finally, prognosis-related miRNAs were utilized to identify target genes, and the functions of the target genes were analyzed for enrichment to investigate the probable mechanisms of the miRNAs. Results: Ten miRNAs were screened through differential analysis to build models: hsa-miR-148a-3p, hsa-miR-223-3p, hsa-miR-331-3p, has-miR-181a-5p, hsa-miR-181b-5p, hsa-miR-181c-5p, hsa-miR-181d-5p, hsa-miR-200a-5p, hsa-miR-141-3p, and hsa-miR-425-5p. The multivariate Cox regression model was an independent prognostic factor (univariate Cox regression results: HR = 3.2642, 95%CI = 1.5773 - 6.7554, P = 0.0014; multivariate Cox regression results: HR = 3.1578, 95%CI = 1.5083 - 6, P = 0.0023). The survival curve of the risk score also revealed that patients with a high risk score had a poor prognosis (P = 2e - 04). The receiver operating characteristic (ROC) curve showed that the model has a certain prediction ability. Batch survival analysis of the miRNAs in the model was conducted and showed that hsa-miR-331-3p (P = 0.0182) was strongly associated with prognosis. Twenty-three predicted target genes were obtained, and Gene Ontology (GO) enrichment analysis showed that these target genes were strongly enriched in transcriptional initiation and cell membrane trafficking. Conclusion: Our research identified a novel miRNA marker for predicting breast cancer patient prognosis and lays the groundwork for future research on necroptosis-related genes.

The Pharmacological Mechanisms of Xiaochaihutang in Treating Breast Cancer Based on Network Pharmacology.

Background: As a classic prescription in Chinese medicine treatment, Xiaochaihutang (XCHT) can improve the clinical effect and reduce serum tumor markers in patients with breast cancer (BC). However, there has not been any study to confirm the mechanism. We used bioinformatics analysis and network pharmacology to find the potential targets. Methods: The differentially expressed genes (DEGs) of BC were identified from the Cancer Genome Atlas (TCGA) dataset. Then, we utilized weighted coexpression network analysis (WGCNA) with the same dataset. The target genes of BC were obtained by comparing genes of DEGs and in significant modules of WGCNA. Drug targets of XCHT from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database were intersected with the targets of BC. The protein-protein interaction (PPI) of the drug targets was analysed by using the STRING database. We utilized the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) enrichment analysis to identify the specific pathways and key target proteins. Receiver operator characteristic (ROC) curve was used as the verification of drug targets. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. Results: We obtained a set of 21 target genes, which mainly encode neurotransmitter receptors or related transporters, such as OPRD1, 5-HT2A, and so on. In addition, enrichment analyses of 21 target genes showed that they were mainly concentrated in pathways related to the nervous system. Molecular docking was performed on the target gene of BC. Six active compounds can enter the active pocket of target gene, namely, naringenin, beta-sitosterol, coumestrol, nuciferine, beta-sitosterol, and protopine, thereby exerting potential therapeutic effects in BC. Conclusions: Our analysis shows that the mechanism of XCHT in the treatment of BC is mainly acting on the neurogenesis in the microenvironment of breast tumor tissue.

Effect of Radiofrequency Ablation with Interventional Therapy of Hepatic Artery on the Recurrence of Primary Liver Cancer and the Analysis of Influencing Factors.

BACKGROUND: The probability of liver cancer recurring in patients after surgery is a serious threat to liver cancer patients. Radiofrequency ablation is widely employed in liver cancer cases. We explored the therapeutic effects and influencing factors of radiofrequency ablation combined with hepatic artery intervention in patients with recurrence of primary liver cancer surgery. METHODS: 90 patients with primary liver cancer postoperative recurrence admitted to our hospital from January 2014 to February 2017 were selected as the research objects. The patients were randomly divided into the control group (n = 45) and combined treatment group (n = 45). The combined treatment group received radiofrequency ablation combined with hepatic artery interventional therapy, and the control group received hepatic artery interventional therapy. The short-term efficacy, AFP levels before and after treatment, and long-term survival results of the two groups were compared. Single-factor and multifactor analyses of the clinical information of the combined treatment group were carried out to find out the factors affecting the therapeutic effect of radiofrequency ablation combined with hepatic artery intervention on patients with recurrence of primary liver cancer. RESULTS: The total effective rate of short-term curative effect of the combined treatment group was higher than the control group, and there was a statistically significant difference existing (P < 0.05). After treatment, two groups of patients' AFP levels were greatly lower than before treatment, the AFP levels of the combined treatment group were significantly lower than the control group, and there was a statistically significant difference (P < 0.05). The survival rates of patients in the combined treatment group at the sixth month, the first year, and the second year after treatment were significantly higher than those of the control group, and there was a statistically significant difference (P < 0.05). The univariate results showed that, in the combined treatment group, there were statistically significant differences between the effective group and the ineffective group in tumor diameter, intact capsule, liver cirrhosis, intrahepatic spread, and tumor adjacent to large blood vessels (P < 0.05). The outcomes of multivariate analysis indicated that tumor diameter ≥ 3 cm, incomplete capsule, intrahepatic spread, and tumor adjacent to large blood vessels were risk factors for ineffective recurrence of patients with primary liver cancer after radiofrequency ablation combined with hepatic artery intervention (P < 0.05). Discussion. Tumor diameter ≥ 3 cm, incomplete capsule, intrahepatic spread, and tumor adjacent to large blood vessels are risk factors for the ineffectiveness of radiofrequency ablation combined with hepatic artery interventional therapy for patients with recurrence of primary liver cancer. It is necessary to increase the range of radiofrequency treatment, increase the temperature of the radiofrequency needle, and strengthen postoperative follow-up interventions based on the specific conditions of the patient's tumor.

Surgical therapy for chronic internal carotid artery occlusion: a systematic review and meta-analysis.

Chronic internal carotid artery occlusion (CICAO) significantly increases the risk of recurrent stroke. Given unfavorable outcomes, revascularization procedures are not generally recommended for CICAO. In the last several years, loads of studies reported successful surgical revascularization for CICAO with promising success rate and favorable short-term outcomes. Meanwhile, due to the lack of high-quality evidence, the safety and efficacy of revascularization procedures remain debatable. This systematic review aims to scrutinize current evidence for the applicability of revascularization for CICAO. We also investigated potential predictors of postoperative prognosis. We searched clinical studies on surgical treatment of CICAO on the Medline, Cochrane library, and Embase databases, published from Jan 1990 to Jan 2021. Surgical operation was restricted to bypass surgery, endarterectomy, endovascular therapy, and hybrid surgery. Controlled clinical studies were included for clinical outcomes. Large-sample single-arm studies were supplemented to assess complications and success rate. Co-primary endpoints were technical success rate and neurological function; secondary endpoints were recurrent stroke/cerebrovascular events, complications, and deaths within follow-up. This systematic review has been registered in PROSPERO (CRD42020181250). One RCT and 5 cohort studies with a total of 465 patients were included in this review. Seven single-arm studies were supplemented for assessing success rate and complications. Bypass surgery presented the highest graft patency of 96% and a low incidence of complications, but no benefits on neurological function, recurrent stroke, or deaths. Endovascular therapy (carotid stenting) was characterized by a relatively lower technical success rate, significant neurological function recovery, and nonsignificant reduction of cerebrovascular events and deaths. Hybrid surgery was considered as a potential treatment for CICAO because of a high technical success rate and significant neurological improvement. Endarterectomy is only suitable for short-segment occlusion. Prospective clinical trials should focus on carotid stenting and hybrid surgery for their significant capacity of improving neurologic function and potential capacity of reducing deaths and cerebrovascular events.

Long non-coding RNA SNHG3 promotes breast cancer cell proliferation and metastasis by binding to microRNA-154-3p and activating the notch signaling pathway.

BACKGROUND: Breast cancer (BC) is a malignant tumor that occurs in the epithelial tissue of the breast gland. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) has been found to promote BC cell proliferation and invasion by regulating the microRNA (miR)-101/zinc-finger enhancer binding axis in BC. Herein, the objective of the present study is to evaluate the effect of lncRNA SNHG3 on BC cell proliferation and metastasis with the Notch signaling pathway. METHODS: Differentially expressed lncRNA in BC tissues and normal breast tissues was analyzed. SNHG3 si-RNA-1 and SNHG3 si-RNA-2 were constructed to detect the mechanism of SNHG3 interference in BC cell proliferation, viability, migration and invasion. Then, dual-luciferase reporter gene assay was utilized to verify the binding relation between SNHG3 and miR-154-3p as well as miR-154-3p and Notch2. Moreover, xenograft transplantation was applied to confirm the in vitro experiments. RESULTS: Highly expressed SNHG3 was observed in BC tissues. The growth of BC cells in vivo and in vitro was evidently repressed after silencing SNHG3. BC cell invasion and migration were inhibited by silencing SNHG3 in vitro. SNHG3 could act as a competing endogenous RNA of miR-154-3p and upregulate the Notch signaling pathway to promote BC cell development. Activation of the Notch signaling pathway can partly reverse the inhibition of cell activity induced by silencing SNHG3. CONCLUSION: Our study demonstrated that interfered lncRNA SNHG3 promoted BC cell proliferation and metastasis by activating the Notch signaling pathway. This investigation may offer new insight for BC treatment.

The protective role of intermedin in promoting angiogenesis during renal fibrosis.

BACKGROUND: Renal fibrosis promotes the progression of chronic renal disease to end-stage renal disease. Microvascular damage and loss play an important role in renal fibrosis. Intermedin (IMD) is expressed mainly in the heart and kidney. IMD has been shown to increase renal blood flow and reduce the loss of glomerular and surrounding renal tubules, but its role in mediating microvascular damage in renal fibrosis remains to be elucidated. Here, we investigated the effects of IMD on microvascular damage in a renal fibrosis model. METHODS: We created a rat model of unilateral ureteral obstruction (UUO) to clarify the effect of microvascular damage on renal fibrosis and the effect of intermedin on reversing renal vascular injury and promoting angiogenesis. Rats were divided randomly into three groups: sham, UUO, and UUO + IMD. The sham group underwent free ureteral ligation but not occlusion. Rats in the latter two groups underwent UUO, and rats in the IMD group were additionally administered intermedin (100 ng/kg/h) daily. On the 7th, 14th, 21st, and 28th days after surgery, abdominal aortic blood and the obstructed kidneys were harvested from the rats (n = 6) for analysis. RESULTS: IMD was found to protect against renal vascular injury and to increase microvessel density. Molecularly, IMD upregulated vascular endothelial growth factor-vascular endothelial growth factor receptor (VEGF-VEGFR2) pathway activity. The VEGF-VEGFR2 pathway might be the underlying mechanism mediating the protective activities of IMD in promoting angiogenesis, delaying renal fibrosis, and improving renal function. CONCLUSION: IMD could be a potential candidate treatment for renal fibrosis.

Urinary fibrinogen is elevated in hospitalized patients undergoing angiography.

OBJECTIVES: Previously, we found that urinary fibrinogen (Fg) levels were positively related to contrast-induced acute renal injury degree in mice. Reduction of fibrinogen in heterozygous mice can improve renal function. Here, we prospectively observed the variation in urinary Fg levels in patients undergoing angiography to determine the relationship between serum creatinine (Scr) and serum cystatin C (Cys C) levels. METHODS: Serum Cys C and urinary Fg levels were evaluated by ELISA before and 2, 12, and 24 h after angiography in 115 enrolled inpatients. Scr was assessed before and 24 and 48 h after angiography. Data were analyzed using ANOVA or Kruskal-Wallis ANOVA and Spearman correlation. RESULTS: Urinary Fg levels were elevated as early as 2 h after angiography and decreased thereafter before returning to baseline levels 24 h after angiography. Urinary Fg was correlated with the amount of contrast agent ( r = 0.24, p = 0.036) and the presence of diabetes and hypertension ( r = 0.31, r = 0.28, p < 0.05, respectively). Urinary Fg levels 2 h after angiography were positively related with Cys C at 12 and 24 h and Scr at 48 h after angiography ( r = 0.34, r = 0.51, r = 0.85, p < 0.05, respectively). CONCLUSIONS: Our results showed that variations in urinary Fg levels are consistent with serum Cys C and Scr in patients undergoing angiography and that urinary Fg levels were the earliest parameter to become elevated. Urinary Fg should be investigated as a useful predictor for abnormal renal function after angiography.

Age-Related Changes in the Natural Killer Cell Response to Seasonal Influenza Vaccination Are Not Influenced by a Synbiotic: a Randomised Controlled Trial.

Natural killer (NK) cells are an important component of the immune response to influenza infection, but are subject to alteration during aging, which may play a role in impaired response to infection and vaccination in older people. Enhancement of NK cell activity could, therefore, present a means to improve the immune response to vaccination in older subjects, and pre- and probiotics offer an opportunity to modulate antiviral defenses via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the NK cell response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial. There were significant effects of aging on NK cell phenotype, the most notable of which were an increase in CD56dim cells, mainly reflected in the CD16+ subset, a decrease in CD56bright cells, mainly reflected in the CD16- subset, and greater expression of the immunosenescence marker, CD57, on NK cell subsets. However, these changes only partially translated to differences in NK cell activity, observed as trends toward reduced NK cell activity in older subjects when analyzed on a per cell basis. Influenza vaccination increased the proportion of CD56bright cells and decreased the proportion of CD56dim cells, in young, but not older subjects. Although NK cell activity in response to vaccination was not significantly different between the young and older subjects, low post-vaccination NK cell activity was associated with poor seroconversion in only the older subjects. There was no influence of the synbiotic on NK cell phenotype or activity, either before or after influenza vaccination. In conclusion, aging is associated with marked alteration of the phenotype of the NK cell population and there was evidence of an impaired NK cell response to influenza vaccination in older subjects. The effects of aging on NK cell phenotype and activity could not be offset by B. longum + Gl-OS. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01066377.