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This study aimed to explore the potential of using mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) pre-treated with Astragaloside IV (ASIV) to alleviate inflammation in high glucose (HG)-damaged endothelial cells. MSC-Exos were isolated from untreated MSCs and ASIV-pre-treated MSCs, and their characteristics were assessed. The expression of miR-146a-5p in MSC-Exos was determined, and it was found that ASIV treatment enhanced its expression. In order to assess the impact of highly miR-146a-5p-expressing MSC-Exos on HG-injured endothelial cells, we established a model of HG-induced inflammation using human umbilical vein endothelial cells (HUVECs). The study measured cell viability, apoptosis, tube formation, and levels of inflammatory cytokines among the different treatment groups. It was found that transferring MSC-Exos with high miR-146a-5p expression to HG-damaged HUVECs increased cell viability and tube formation ability while reducing the number of apoptotic cells. Additionally, changes in inflammatory factors indicated a reduction in the inflammatory response. Further investigation demonstrated that miR-146a-5p inhibited the expression of TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB, which are involved in the inflammatory response. This resulted in the alleviation of inflammation in HG-damaged endothelial cells. In summary, our findings indicate that ASIV treatment stimulated the secretion of MSC-Exos that exhibited increased levels of miR-146a-5p. These exosomes, in turn, regulated the TRAF6/NF-κB pathway. As a result of this modulation, the inflammatory response in HG-damaged endothelial cells was alleviated. These findings offer a fresh approach to addressing vascular complications associated with diabetes, which could lead to novel treatment strategies in the field.
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In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body's antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies.
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BACKGROUND: With the increasing importance of thermal ablation (TA) in hepatocellular carcinoma (HCC) treatment, local tumor progression (LTP) has become a nonignorable recurrence type after ablation. PURPOSES: To analyze the influence of peritumoral liver parenchyma on LTP and to explore the possible reasons for this influence. METHODS: Ablated HCCs with peritumoral parenchymal biopsy and ablation margins greater than 5 mm were included from two hospitals. The grade of necroinflammatory activity (G) and stage of fibrosis (S) of the parenchyma were evaluated by Scheuer staging system. Univariate/multivariate Cox model was used to analyze the possible factors influencing LTP. Peritumoral satellite focus rate, ablation energy, ablation volume after treatment, ablation volume after one-month, and volume reduction rate were collected and analyzed to explore the possible reasons for influence. Propensity score matching (PSM) was used to balance baselines across different groups. RESULTS: 346 HCCs (64 with LTP, 282 without LTP) were enrolled from January 2013 to June 2022, with a median follow-up of 27 months. Univariate/multivariate analysis showed fibrosis was a protective factor in LTP (OR = 0.70, 95%CI: 0.55-0.89). The low-fibrosis group exhibited higher satellite focus rate (15.6% vs. 8.4%, p = 0.048), lower ablation energy (22637 ± 9424 J vs. 33352 ± 13779 J, p < 0.001) and higher volume reduction rate (0.33 ± 0.06 vs. 0.25 ± 0.06, p < 0.001) than the high-fibrosis group. Therefore, we speculated that the protective effect of fibrosis was due to its blocking of tumor invasion and reduction of sublethal zones. CONCLUSION: Fibrosis of the peritumoral liver parenchyma is a stable protective factor in LTP occurrence.
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BACKGROUND: The effect of microwave ablation (MWA) for the renal cell carcinoma (RCC) in Von Hippel-Lindau (VHL) disease is unclear. OBJECTIVE: To assess the safety, Technique efficacy, renal function and oncological outcome of MWA for RCC in VHL patients. METHODS: Consecutive patients with RCCs in VHL disease treated by MWA were retrospectively collected from November 2009 to October 2020. The technical efficacy rate and complications were assessed. The outcomes of pre- and post-ablative eGFR were compared. The local recurrent-free survival (LRFS), renal-cancer-free survival (RCFS), cancer-specific survival (CSS), overall survival (OS) and complications were presented. RESULTS: A total of 10 patients (mean age, 39.0 years ± 10.7 [SD]; 3 women) with 28 RCCs (mean tumor size, 3.0 cm ± 0.34; mean tumor volume, 20.7 mL ± 43.3) treated with MWA were included. Th median follow-up time was 52 months(IQR:27-80). The overall technical efficacy rate was 100% with no major complications occurred. No significant statistical difference between pre-ablative and postablative creatinine level (102.0 µmol/L ± 30.4 vs 112.3 µmol/L ± 38.7, p = 0.06), but the pre-ablative eGFR level was significantly higher than the post-ablative eGFR (78.0 mL/(min*1.73m2) ± 28.6 vs 72 mL/(min*1.73m2) ± 31.4, p = 0.04), with the mean decrease of 5.86 ml/(min*1.73m2). The local recurrent-free survival(LRFS) and renal-cancer-free survival (RCFS) were 100% and 60%, respectively. The cancer specifical survival (CSS) and overall survival (OS) were 95.5% and 100%, respectively. CONCLUSION: Microwave ablation is a safe and feasible method for the treatment of RCC in VHL disease, preserving renal function and yielding satisfactory oncological outcomes.
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Carcinoma de Células Renais , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Feminino , Adulto , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/cirurgia , Doença de von Hippel-Lindau/patologia , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologiaRESUMO
Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post-treatment. This meta-analysis investigated the relationship between the post-PCI triglyceride-glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random-effects models. Cluster-robust standard errors crafted the dose-response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post-PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65-2.52; I2 = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34-2.46; I2 = 92%), 2.57 for non-fatal MI (95% CI 1.49-4.41; I2 = 63%), and 2.06 for revascularization (95% CI 1.23-3.50; I2 = 90%). A linear relationship between TyG index and MACE risk was established (R2 = 0.6114). For all-cause mortality, the HR was 1.93 (95% CI 1.35-2.75; I2 = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non-fatal MI but low certainty for all-cause mortality, revascularization, and MACE. The TyG index may predict risks of post-PCI MACE, all-cause mortality, non-fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post-PCI was identified. Future research should validate these findings.
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Glicemia , Intervenção Coronária Percutânea , Triglicerídeos , Humanos , Triglicerídeos/sangue , China/epidemiologia , Glicemia/metabolismo , Glicemia/análise , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/sangue , Biomarcadores/sangueRESUMO
OBJECTIVE: N-wire phantom-based ultrasound probe calibration has been used widely in many freehand tracked ultrasound imaging systems. The calibration matrix is obtained by registering the coplanar point cloud in ultrasound space and non-coplanar point cloud in tracking sensor space based on the least squares method. This method is sensitive to outliers and loses the coplanar information of the fiducial points. In this article, we describe a coplanarity-constrained calibration algorithm focusing on these issues. METHODS: We verified that the out-of-plane error along the oblique wire in the N-wire phantom followed a normal distribution and used it to remove the experimental outliers and fit the plane with the Levenberg-Marquardt algorithm. Then, we projected the points to the plane along the oblique wire. Coplanarity-constrained point cloud registration was used to calculate the transformation matrix. RESULTS: Compared with the other two commonly used methods, our method had the best calibration precision and achieved 25% and 36% improvement of the mean calibration accuracy than the closed-form solution and in-plane error method respectively at depth 16. Experiments at different depths revealed that our algorithm had better performance in our setup. CONCLUSION: Our proposed coplanarity-constrained calibration algorithm achieved significant improvement in both precision and accuracy compared with existing algorithms with the same N-wire phantom. It is expected that calibration accuracy will improve when the algorithm is applied to all other N-wire phantom-based calibration procedures.
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Algoritmos , Imageamento Tridimensional , Imageamento Tridimensional/métodos , Calibragem , Ultrassonografia/métodos , Imagens de FantasmasRESUMO
Background and ethnopharmacological relevance: The morbidity and mortality of cardiovascular diseases (CVDs) are among the highest of all diseases, necessitating the search for effective drugs and the improvement of prognosis for CVD patients. Paeoniflorin (5beta-[(Benzoyloxy)methyl] tetrahydro-5-hydroxy-2-methyl-2,5-methano-1H-3,4-dioxacyclobuta [cd] pentalen-1alpha (2H)-yl-beta-D-glucopyranoside, C23H28O11) is mostly derived from the plants of the family Paeoniaceae (a single genus family) and is known to possess multiple pharmacological properties in the treatment of CVDs, making it a promising agent for the protection of the cardiovascular system. Aim of the study: This review evaluates the pharmacological effects and potential mechanisms of paeoniflorin in the treatment of CVDs, with the aim of advancing its further development and application. Methods: Various relevant literatures were searched in PubMed, ScienceDirect, Google Scholar and Web of Science. All eligible studies were analyzed and summarized in this review. Results: Paeoniflorin is a natural drug with great potential for development, which can protect the cardiovascular system by regulating glucose and lipid metabolism, exerting anti-inflammatory, anti-oxidative stress, and anti-arteriosclerotic activities, improving cardiac function, and inhibiting cardiac remodeling. However, paeoniflorin was found to have low bioavailability, and its toxicology and safety must be further studied and analyzed, and clinical studies related to it must be carried out. Conclusion: Before paeoniflorin can be used as an effective therapeutic drug for CVDs, further in-depth experimental research, clinical trials, and structural modifications or development of new preparations are required.
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ETHNOPHARMACOLOGICAL RELEVANCE: Polydatin is a bioactive ingredient extracted from the roots of the Reynoutria japonica Houtt, and it is a natural precursor of resveratrol. Polydatin is a useful inhibitor of inflammation and acts as a regulator of lipid metabolism. However, the specific mechanisms of action of polydatin in atherosclerosis (AS) remains poorly explained. AIM OF THE STUDY: The aim of this study was to assess the efficacy of polydatin on inflammation induced by the inflammatory cell death and autophagy in AS. MATERIALS AND METHODS: Apolipoprotein E knockout (ApoE-/-) mice were fed with a high-fat diet (HFD) for 12 weeks to induce the formation of atherosclerotic lesions. The ApoE-/- mice were then randomly divided into the following six groups: (1) model group, (2) simvastatin group, (3) MCC950 group, (4) low dose polydatin group (Polydatin-L), (5) medium dose polydatin group (Polydatin-M), (6) and high dose polydatin group (Polydatin-H). The C57BL/6J mice were treated as controls and administered a standard chow diet. All mice were gavaged once daily for 8 weeks. The distribution of aortic plaques was observed by En Oil-red-O staining and hematoxylin and eosin staining (H&E). Oil-red-O staining was used to observe lipid content in the aortic sinus plaque; Masson trichrome staining was used to gauge collagen content in the plaque; and immunohistochemistry was used to evaluate smooth muscle actin (α-SMA) and CD68 macrophages marker expression levels in the plaque, which were used to assess the vulnerability index of the plaque. The lipid levels were measured using an enzymatic assay with an automatic biochemical analyzer. The level of inflammation was detected by enzyme-linked-immunosorbent assay (ELISA). Autophagosomes were detected by transmission electron microscopy (TEM). Pyroptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)/caspase-1 and other proteins related to the expression levels of autophagy and pyroptosis were detected by Western blot analysis. RESULTS: Nucleotide oligomerization (NOD)-like receptor (NLR) family pyrin domain-containing protein 3 (NLRP3) inflammasome activation leads to pyroptosis, including the cleavage of caspase-1, interleukin (IL)-1ß and IL-18 production, and the co-expression of TUNEL/caspase-1-all of these are inhibited by polydatin, whose inhibitory effect is similar to that of MCC950, a specific inhibitor of NLRP3. Further, polydatin decreased the protein expression of NLRP3 and the phosphorylated mammalian target of rapamycin (p-mTOR), and increased the number of autophagosomes as well as the increased the cytoplasmic microtubule-associated protein light chain 3 (LC3)/autophagosome membrane-type LC3 ratio. Moreover, the protein expression levels of p62 decreased, suggesting that polydatin can increase autophagy. CONCLUSIONS: Polydatin can inhibit the activation of the NLRP3 inflammasome and cleavage of caspase-1, thereby inhibiting pyroptosis and secretion of inflammatory cytokines, and promoting autophagy through NLRP3/mTOR pathway in AS.
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Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , Inflamassomos/metabolismo , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos Endogâmicos C57BL , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Autofagia , Serina-Treonina Quinases TOR , Inflamação/tratamento farmacológico , Caspase 1/metabolismo , Apolipoproteínas E/genética , Lipídeos/farmacologia , Mamíferos/metabolismoRESUMO
Maxillofacial arteriovenous malformation located in the sensitive parts of the nose and lips has been an arduous challenge for doctors to meet a balance between resection and aesthetics in one time. In this report, one patient with a giant arteriovenous malformation covering the forehead, the nose, the lip, and bilateral cheeks and resulting in the appearance of the face like a lion's face, can not meet satisfactory outcomes by other therapeutic methods. We successfully reduced the size of vascular lesion using low-power and short-duration microwave ablation under real-time ultrasound guidance. In the two-year follow-up, the patient's face almost recovered to normality. Microwave ablation is expected to be a new alternative therapy for the treatment of maxillofacial arteriovenous malformations. Laryngoscope, 133:2984-2987, 2023.
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Malformações Arteriovenosas , Embolização Terapêutica , Humanos , Micro-Ondas/uso terapêutico , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Nariz , Testa , Embolização Terapêutica/efeitos adversosRESUMO
For the diagnosis and therapy of small cell lung cancer (SCLC), the accurate and sensitive determination of neuron-specific enolase (NSE) content is crucial. This work outlines a dual-quenching electrochemiluminescence resonance energy transfer (ECL-RET) immunosensor based on the double quenching effects of iron base metal organic frameworks (FeMOFs) loaded with small sized CuO nanoparticles (FeMOFs-sCuO) towards CoPd nanoparticles (CoPdNPs) enhanced porous g-C3N4 (P-C3N4-CoPdNPs). To be specific, we prepared a porous g-C3N4 (P-C3N4) which has a rich porous structure, and significantly increased the specific surface area and the number of reaction sites of P-C3N4. Meanwhile, the CoPdNPs were loaded onto P-C3N4 to improve the ECL luminescence property of P-C3N4/K2S2O8 system through acting as a coreaction accelerator. In addition, the ultraviolet-visible (UV-vis) absorption spectra of FeMOFs and small sized CuO nanoparticles (sCuO) showed considerable overlap with the ECL emission spectra of P-C3N4 appropriately. Therefore, FeMOFs with high specific surface area were prepared and well combined with sCuO to effectively dual-quenching the ECL emission of P-C3N4 based on resonance energy transfer. Hence, a new type ECL-RET couple made up of P-C3N4-CoPdNPs (donor) and FeMOFs-sCuO (acceptor) were developed for the first time. A certain amount of P-C3N4-CoPdNPs, Ab1, BSA, NSE were modified layer by layer onto the electrode surface. Then FeMOFs-sCuO-Ab2 bioconjugates was incubated through the immune recognition binding. As a result, a sandwich-type ECL biosensor was manufactured successfully for NSE immunoassay. Under optimal experimental conditions, the limit of detection (LOD) and the limit of quantitation (LOQ) of the prepared ECL sensor for NSE analysis was 20.4 fg mL-1 and 7.99 fg mL-1, respectively, with the relative standard deviation (RSD) of 1.68%. The linear detection range was 0.0000500-100 ng mL-1. The studied immunosensor had satisfactory sensitivity, specificity and reproducibility, manifesting the suggested sensing strategy might offer a good technical means and theoretical basis for the sensitivity analysis of NSE and has a potential application in clinical diagnosis analysis.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Nanopartículas , Reprodutibilidade dos Testes , Porosidade , Medições Luminescentes , Imunoensaio , Nanopartículas/química , Transferência de Energia , Fosfopiruvato Hidratase , Técnicas Eletroquímicas , Nanopartículas Metálicas/química , Limite de DetecçãoAssuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Veias Hepáticas/cirurgiaRESUMO
Increasing researches have considered gut microbiota as a new "metabolic organ," which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.
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Atherosclerosis (AS) is chronic pathological process based on the inflammatory reaction associated with factors including vascular endothelial dysfunction, inflammation, and autoimmunity. Inflammasomes are known to be at the core of the inflammatory response. As a pattern recognition receptor of innate immunity, the NLRP3 inflammasome mediates the secretion of inflammatory factors by activating the Caspase-1, which is important for maintaining the immune system and regulating the gut microbiome, and participates in the occurrence and development of AS. The intestinal microecology is composed of a large number of complex structures of gut microbiota and its metabolites, which play an important role in AS. The gut microbiota and its metabolites regulate the activation of the NLRP3 inflammasome. Targeting the NLRP3 inflammasome and regulating intestinal microecology represent a new direction for the treatment of AS. This paper systematically reviews the interaction between the NLRP3 inflammasome and gut microbiome in AS, strategies for targeting the NLRP3 inflammasome and gut microbiome for the treatment of AS, and provides new ideas for the research and development of drugs for the treatment of AS.
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Aterosclerose , Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamassomos , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLRRESUMO
Background: Exploring the potential biological relationships between heart failure with preserved ejection fraction (HFpEF) and concomitant diseases has been the focus of many studies for the establishment of personalized therapies. Hypertension (HTN) is the most common concomitant disease in HFpEF patients, but the functional connections between HFpEF and HTN are still not fully understood and effective treatment strategies are still lacking. Methods: In this study, tandem mass tag (TMT) quantitative proteomics was used to identify disease-related proteins and construct disease-related networks. Furthermore, functional enrichment analysis of overlapping network modules was used to determine the functional similarities between HFpEF and HTN. Molecular docking and module analyses were combined to identify therapeutic targets for HFpEF and HTN. Results: Seven common differentially expressed proteins (co-DEPs) and eight overlapping modules were identified in HFpEF and HTN. The common biological processes between HFpEF and HTN were mainly related to energy metabolism. Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were all closely associated with HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate were best matched with the co-DEPs by molecular docking analyses. Conclusion: Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were the main functional connections between HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate could potentially be effective for the treatment of HTN and HFpEF.
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Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels, leading to arthritis, abdominal pain, and renal involvement. However, scrotal involvement is a rare complication of HSP and scrotal pain. Swelling is the most frequent clinical presentation and can be easily confused with testicular torsion. If not treated in time, the scrotal inflammation will result in irreversible testicular necrosis. We report a 6-year-old male with HSP and scrotal involvement, characterized by swelling and pain on the left side of the scrotum, rashes on both lower extremities, and epididymitis. He was treated with conservative care, corticosteroids, and antibiotic therapy. We were able to avoid surgical intervention. On the 10 days of treatment, he recovered sufficiently well and was discharged. We have reviewed the literature related to HSP with scrotal involvement, identified 21 cases, and revealed that steroid therapy and/or antibiotics are the first-line of therapy in children with scrotal involvement. Vasculitis in the scrotum may predispose to testicular torsion, which is a complication that should not be overlooked. Clinicians should be aware of the atypical types of HSP. Timely diagnosis and appropriate treatment are essential for achieving the best results.
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Vasculite por IgA/patologia , Escroto/patologia , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Criança , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/diagnóstico , Vasculite por IgA/tratamento farmacológico , Masculino , Escroto/efeitos dos fármacos , Torção do Cordão Espermático/etiologiaRESUMO
BACKGROUND: Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. METHODS: The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. RESULTS: A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1ß, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1ß, MMP-2 and MMP-9 in rats. CONCLUSION: The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.
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BACKGROUND: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. METHODS: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. RESULTS: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. CONCLUSIONS: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.
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Cardiomegalia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Insuficiência Cardíaca , Miócitos Cardíacos/metabolismo , Volume Sistólico/efeitos dos fármacos , Administração Oral , Animais , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Cardiomegalia/microbiologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Fibrose , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/microbiologia , Insuficiência Cardíaca/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos DahlRESUMO
OBJECTIVE: To compared the efficacy of laparoscopy- assisted radiofrequency ablation (LRFA) and percutaneous radiofrequency ablation (PRFA) for the treatment of hepatocellular carcinoma (HCC). METHODS: Between September, 2013 and September, 2016, a total of 60 HCC patients with 78 tumor nodules underwent LRFA (30 cases with 46 tumor nodules) and PRFA (30 cases with 32 tumor nodules) in our hospital. The patients were followed up for 3 years to compare the complete ablation rate, serious complications, recurrence rate and long-term survival rate between the two groups. RESULTS: The patients receiving LRFA had a complete ablation rate of 95.65% (44/46), significantly higher than the rate of 93.75% (30/32) in PRFA group (P > 0.05). Significant differences were found between LRFA and PRFA groups in the incidence of serious complications [0 vs 6.7% (2/30), P < 0.05] and recurrence rate [13.33% (4/30) vs 23.33% (7/30), P < 0.05]. The 1-and 3-year overall survival rates of the patients were 96.15% and 55.12% in LRFA group and 93.73% and 48.54% in PRFA group, respectively (P > 0.05). CONCLUSIONS: Both LRFA and PRFA are effective for HCC treatment, but is associated with a lower recurrence rate, fewer serious complications, a better treatment safety and a better applicability for tumor in difficult locations.
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Carcinoma Hepatocelular/cirurgia , Laparoscopia , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência/métodos , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The high prevalence of hepatitis B virus (HBV) imposes a huge burden of hepatocellular carcinoma (HCC) in Asia. Surgical resection remains an important therapeutic strategy for HCC. Hepatic inflow occlusion, known as the Pringle maneuver, is the most commonly used method of reducing blood loss during liver parenchymal transection. A major issue with this maneuver is ischemia-reperfusion injury to the remnant liver, and the hemodynamic disturbance it induces in the tumor-bearing liver raises an oncological concern. Given the technical advances in living donor liver transplantation, vascular occlusion in liver resection can be avoided in experienced hands. The aim of this study is to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with hepatic inflow occlusion. METHODS/DESIGN: This study will include eligible patients with HBV-related HCC elected for liver resection. Fifty-seven patients will be enrolled in each randomization arm to detect a 20 % difference in the serum level of total bilirubin on postoperative day 5 (80 % power and α = 0.05). The secondary endpoints include procedural parameters, perioperative liver function and inflammatory response, postoperative morbidity and mortality, and long-term outcomes. Patients will be followed for up to 5 years. Data will be statistically analyzed on an intention-to-treat basis. DISCUSSION: This prospective randomized controlled trial is designed to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with vascular occlusion. The clinical implications of these outcomes may change current surgical practice and fill the oncological gaps therein. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02563158 . Registered on 28 September 2015.