Meta-Analysis of Single-Cell RNA-Seq Data Reveals the Mechanism of Formation and Heterogeneity of Tertiary Lymphoid Organ in Vascular Disease.

BACKGROUND: Tertiary lymphoid organs (TLOs) are ectopic lymphoid organs developed in nonlymphoid tissues with chronic inflammation, but little is known about their existence in different types of vascular diseases and the mechanism that mediated their development. METHODS: To take advantage of single-cell RNA sequencing techniques, we integrated 28 single-cell RNA sequencing data sets containing 5 vascular disease models (atherosclerosis, abdominal aortic aneurysm, intimal hyperplasia, isograft, and allograft) to explore TLOs existence and environment supporting its growth systematically. We also searched Medline, Embase, PubMed, and Web of Science from inception to January 2022 for published histological images of vascular remodeling for histological evidence to support TLO genesis. RESULTS: Accumulation and infiltration of innate and adaptive immune cells have been observed in various remodeling vessels. Interestingly, the proportion of such immune cells incrementally increases from atherosclerosis to intimal hyperplasia, abdominal aortic aneurysm, isograft, and allograft. Importantly, we uncovered that TLO structure cells, such as follicular helper T cells and germinal center B cells, present in all remodeled vessels. Among myeloid cells and lymphocytes, inflammatory macrophages, and T helper 17 cells are the major lymphoid tissue inducer cells which were found to be positively associated with the numbers of TLO structural cells in remodeled vessels. Vascular stromal cells also actively participate in vascular TLO genesis by communicating with myeloid cells and lymphocytes via CCLs (C-C motif chemokine ligands), CXCL (C-X-C motif ligand), lymphotoxin, BMP (bone morphogenetic protein) chemotactic, FGF-2 (fibroblast growth factor-2), and IGF (insulin growth factor) proliferation mechanisms, particularly for lymphoid tissue inducer cell aggregation. Additionally, the interaction between stromal cells and immune cells modulates extracellular matrix remodeling. Among TLO structure cells, follicular helper T, and germinal center B cells have strong interactions via TCR (T-cell receptor), CD40 (cluster of differentiation 40), and CXCL signaling, to promote the development and maturation of the germinal center in TLO. Consistently, by reviewing the histological images from the literature, TLO genesis was found in those vascular remodeling models. CONCLUSIONS: Our analysis showed the existence of TLOs across 5 models of vascular diseases. The mechanisms that support TLOs formation in different models are heterogeneous. This study could be a valuable resource for understanding and discovering new therapeutic targets for various forms of vascular disease.

The regulatory role of metabolic organ-secreted factors in the nonalcoholic fatty liver disease and cardiovascular disease.

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disease characterized by an excessive accumulation of fat in the liver, which is becoming a major global health problem, affecting about a quarter of the population. In the past decade, mounting studies have found that 25%-40% of NAFLD patients have cardiovascular disease (CVD), and CVD is one of the leading causes of death in these subjects. However, it has not attracted enough awareness and emphasis from clinicians, and the underlying mechanisms of CVD in NAFLD patients remain unclear. Available research reveals that inflammation, insulin resistance, oxidative stress, and glucose and lipid metabolism disorders play indispensable roles in the pathogenesis of CVD in NAFLD. Notably, emerging evidence indicates that metabolic organ-secreted factors, including hepatokines, adipokines, cytokines, extracellular vesicles, and gut-derived factors, are also involved in the occurrence and development of metabolic disease and CVD. Nevertheless, few studies have focused on the role of metabolic organ-secreted factors in NAFLD and CVD. Therefore, in this review, we summarize the relationship between metabolic organ-secreted factors and NAFLD as well as CVD, which is beneficial for clinicians to comprehensive and detailed understanding of the association between both diseases and strengthen management to improve adverse cardiovascular prognosis and survival.

Patients' perspectives on, experience with and concerns about crohn's disease: insights from Chinese social media.

AIM: The aim of this study was to explore the experience and perceptions of patients with Crohn's disease in China. METHODS: Data mining was used to investigate posts in Crohn's disease online medical communities. The data were collected through the crawler code, and latent Dirichlet allocation (LDA) and grounded theory were used to mine the theme features after data cleaning. RESULTS: In analyzing the topic characteristics of online posts, LDA divided 6757 posts into 15 topics on four aspects: seeking disease information, making decisions on medication use, psychological burden, and communicating about diet and nutrition. CONCLUSION: Overall, social media is patient-centric and helps us better understand the experiences and perceptions of patients. This study can help medical staff predict the thoughts and concerns of Crohn's disease patients during the treatment process, facilitate doctor-patient communication, and assist in the formulation of medical policies.

Clinical characteristics and prognosis differences between isolated right and left ventricular myocardial infarction in the Chinese population: a retrospective study.

Background and aims: Acute myocardial infarction (AMI) is divided into left ventricular myocardial infarction (LVMI) and right ventricular myocardial infarction (RVMI) according to the regions of myocardial ischemic necrosis. Clinical characteristics, treatment strategies, and prognosis differences between isolated RVMI and LVMI have not been well characterized. This study aimed to explore this difference of patients with isolated RVMI and LVMI. Methods: This retrospective cohort study included 3,506 patients hospitalized with coronary angiography diagnosed type 1 myocardial infarction (MI). Characteristics of admission and treatment strategies were compared in patients with isolated RVMI and LVMI. COX proportional hazards models with and without inverse probability of treatment weighting (IPTW) adjustment were performed to estimate the difference in all-cause and cardiovascular mortality between the two groups. Results: In this retrospective study, we found the frequency of isolated RVMI was significantly lower in the population than that of isolated LVMI (406 (11.6%) vs 3,100 (88.4%)). Patients with isolated RVMI have similar age, sex, and comorbidities to the patients with isolated LVMI. However, patients with isolated RVMI have lower heart rate and blood pressure, but higher rates of cardiogenic shock and atrioventricular block. It is noteworthy that patients with isolated RVMI are more likely to be complicated with the multivessel lesion. Patients with isolated RVMI have lower risk of all-cause mortality (HR 0.36; 95% CI [0.24-0.54], p < 0.001) and cardiovascular mortality (HR 0.37; 95% CI [0.22-0.62], p < 0.001) than patients with isolated LVMI. Conclusions: This study showed that patients with isolated RVMI and LVMI have similar baseline characteristics. However, the clinical manifestations were different in the isolated RVMI and LVMI patients. This study revealed a better prognosis of isolated RVMI patients compared to isolated LVMI, which indicates the ischemic region could be considered in AMI risk stratification models for better assessment of risk for adverse clinical events.

Sepsis as an independent risk factor in atrial fibrillation and cardioembolic stroke.

Background: Electrolyte balance is an important factor to sustain the homeostasis of human body environment and in sepsis pathogenesis. Many current cohort-based studies have already revealed that electrolyte disorder may intensify sepsis and induce stroke. However, the corresponding randomized controlled trials did not show that electrolyte disorder in sepsis has a harmful effect on stroke. Objectives: The aim of this study was to examine the association of genetically sepsis-derived electrolyte disorder with stroke risk using meta-analysis and Mendelian randomization. Results: In four studies (182,980 patients), electrolyte disorders were compared with stroke incidence in patients with sepsis. The pooled odds ratio (OR) of stroke is 1.79 [95% confidence interval (CI): 1.23-3.06; p < 0.05], which shows a significant association between electrolyte disorder and stroke in sepsis patients. Furthermore, in order to evaluate the causal association between stroke risk and sepsis-derived electrolyte disorder, a two-sample Mendelian randomization (MR) study was conducted. The genetic variants extracted from a genome-wide association study (GWAS) of exposure data that are strongly associated with frequently used sepsis were used as instrumental variables (IVs). Based on the IVs' corresponding effect estimates, we estimated overall stroke risk, cardioembolic stroke risk, and stroke induced by large/small vessels from a GWAS meta-analysis with 10,307 cases and 19,326 controls. As a final step to verify the preliminary MR results, we performed sensitivity analysis using multiple types of Mendelian randomization analysis. Conclusion: Our study revealed the association between electrolyte disorder and stroke in sepsis patients, and the correlation between genetic susceptibility to sepsis and increased risk of cardioembolic stroke, hinting that cardiogenic diseases and accompanying electrolyte disorder interference in due course could help sepsis patients get more benefits in stroke prevention.

Endoscopic submucosal dissection for early signet ring cell gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The use of endoscopic submucosal dissection (ESD) for treating early signet ring cell carcinoma (SRC) is controversial due to the risk of lymph node metastasis. AIM: To carry out a meta-analysis to evaluate ESD for therapeutic efficacy and safety in early signet ring cell gastric cancer. METHODS: The PubMed, Web of Science, Cochrane Library, and EMBASE databases were used to search for relevant studies evaluating the therapeutic efficacy and safety of ESD in SRC. The rates of recurrence, complete resection, incomplete resection, curative resection, en bloc resection, and adverse events were extracted and analyzed. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated by the Egger's test. Institutional review board approval and written consent were not needed for this report. RESULTS: This meta-analysis enrolled seven studies with 653 participants undergoing ESD treatment for early SRC. The overall recurrence rate was 0.010 [95% confidence interval (CI): 0.000-0.040, Z = 1.422, P = 0.155]. The total lymphovascular invasion rate was 0.038 (95%CI: 0.007-0.088, Z = 3.026, P = 0.002). The total en bloc resection rate was estimated at 0.984 (95%CI: 0.925-1.000, Z = 19.463, P = 0.000). The total complete and incomplete resection rates were estimated at 0.785 (95%CI: 0.596-0.928, Z = 9.789, P = 0.000) and 0.188 (95%CI: 0.016-0.468, Z = 2.531, P = 0.011), respectively. The total procedure-associated gastric hemorrhage and perforation rates were estimated at 0.026 (95%CI: 0.005-0.061, Z = 3.006 P = 0.003) and 0.004 (95%CI: 0.000-0.028, Z = 0.938, P = 0.348), respectively. The curative resection, vertical margin invasion, and lateral margin invasion rates were 72.1% (145/341), 2.3% (8/348), and 34.45% (41/119), respectively. CONCLUSION: ESD constitutes a promising therapeutic approach for early undifferentiated SRC gastric cancer. However, further improvements are required for increasing its treatment efficacy and reducing adverse outcomes.

CD8-positive indolent T-Cell lymphoproliferative disorder of the gastrointestinal tract: A case report and review of literature.

BACKGROUND: Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPD-GI), a primary tumor forming in the gastrointestinal (GI) tract, represents a rarely diagnosed clonal T-cell disease with a protracted clinical course. CASE SUMMARY: This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation. Postsurgical histopathological analysis, combined with hematoxylin-eosin staining, immunohistochemistry and TCRß/γ clonal gene rearrangement test, confirmed the diagnosis of CD8+ ITLPD-GI. CONCLUSION: Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize. So far, indolent CD8+ ITLPD-GI has not been comprehensively examined. The current mini-review focused on evaluating indolent CD8+ ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis, detection of genetic and epigenetic alterations, and therapeutic target identification.

Laparoscopic-assisted endoscopic full-thickness resection of a large gastric schwannoma: A case report.

BACKGROUND: Schwannomas, also known as neurinomas, are benign tumors derived from Schwann cells. Gastrointestinal schwannomas are rare and are most frequently reported in the stomach. They are usually asymptomatic and are difficult to diagnose preoperatively; however, endoscopy and imaging modalities can provide beneficial preliminary diagnostic data. There are various surgical options for management. Here, we present a case of a large gastric schwannoma (GS) managed by combined laparoscopic and endoscopic surgery. CASE SUMMARY: A 28-year-old woman presented with a 2-mo history of epigastric discomfort and a feeling of abdominal fullness. On upper gastrointestinal endoscopy and endoscopic ultrasonography, a hypoechogenic submucosal mass was detected in the gastric antrum: It emerged from the muscularis propria and projected intraluminally. Computed tomography showed a nodular lesion (4 cm × 3.5 cm), which exhibited uniform enhancement, on the gastric antrum wall. Based on these findings, a preliminary diagnosis of gastrointestinal stromal tumor was established, with schwannoma as a differential. Considering the large tumor size, we planned to perform endoscopic resection and to convert to laparoscopic treatment, if necessary. Eventually, the patient underwent combined laparoscopic and gastroscopic surgery. Immunohistochemically, the resected specimen showed positivity for S-100 and negativity for desmin, DOG-1, α-smooth muscle actin, CD34, CD117, and p53. The Ki-67 index was 3%, and a final diagnosis of GS was established. CONCLUSION: Combined laparoscopic and endoscopic surgery is a minimally invasive and effective treatment option for large GSs.

Trametes robiniophila Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment.

Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo. Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-ß and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8+ T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8+ T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8+ T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.

Identification of AKIRIN2 as a potential biomarker and correlation with immunotherapy in gastric adenocarcinoma by integrated bioinformatics analysis.

Gastric adenocarcinoma is major type of gastric cancer that endangers human health. AKIRIN2 has been shown to be associated with cholangiocarcinoma promoting invasion and angiogenesis. In this study, AKIRIN2 is highly expressed in Gastric adenocarcinoma through bioinformatics analysis based on Stomach adenocarcinoma samples data from The Cancer Genome Atlas. Correlation analysis showed that the high-expression of AKIRIN2 was associated with poor survival rate compared to the low-expression group. Univariate and multivariate Cox regression analyses determined the correlation between clinical characteristics and overall survival. Next, the correlation between AKIRIN2 and immune infiltration was evaluated. The distribution of 24 immune cells and their correlation with the expression of AKIRIN2 were explored using the immune cell database. In addition, three Immune cell methods were used to verify the positive correlation between immune cells and AKIRIN2. Also, Genomics of Drug Sensitivity in Cancer database was utilized to verify the correlation between AKIRIN2 expression level and the efficacy of chemotherapy and immunotherapy. The results showed that AKIRIN2 is an effective biomarker of Gastric adenocarcinoma prognosis, which can guide chemotherapy and immunotherapy and clarify the progress of Gastric adenocarcinoma promoted by immune microenvironment.

Peroral endoscopic longer vs shorter esophageal myotomy for achalasia treatment: A systematic review and meta-analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) has been demonstrated to be safe and effective in the treatment of achalasia. Longer myotomy is the standard POEM procedure for achalasia but when compared with shorter myotomy, its effectiveness is not as well known. AIM: To compare the clinical effectiveness of longer and shorter myotomy. METHODS: PubMed, EmBase, Cochrane Library, web of science and clinicaltrials.gov were queried for studies comparing shorter and longer POEM for achalasia treatment. The primary outcome was clinical success rate. Secondary outcomes comprised of operative time, adverse events (AEs) rate, gastroesophageal reflux disease (GERD) and procedure-related parameters. The Mantel-Haenszel fixed-effects model was primarily used for the analysis. Publication bias was assessed. RESULTS: Six studies were included in this analysis with a total of 514 participants. During the follow-up period of 1-28.7 mo, longer and shorter myotomy in treating achalasia showed similar excellent effectiveness [overall clinical success (OR = 1, 95%CI: 0.46-2.17, P = 1, I2: 0%; subgroup of abstract (OR = 1.19, 95%CI: 0.38 to 3.73; P = 0.76; I2: 0%); subgroup of full text (OR = 0.86 95%CI: 0.30 to 2.49; P = 0.78; I2: 0%)]. Shorter myotomy had significantly reduced mean operative time compared with the longer procedure. There were no statistically significant differences in AEs rates, including GERD (overall OR = 1.21, 95%CI: 0.76-1.91; P = 0.42; I2: 9%; subgroup of abstract OR = 0.77, 95%CI: 0.40-1.47; P = 0.43; I2: 0%; subgroup of full text OR = 1.91, 95%CI: 0.98-3.75; P = 0.06; I2: 0%), hospital stay (overall MD = -0.07, 95%CI: -0.30 to 0.16; P = 0.55; I2: 24%; subgroup of abstract MD = 0.20, 95%CI: -0.25 to 0.65; P = 0.39; I2: 0; subgroup of full text MD = -0.16, 95%CI: -0.42 to 0.10; P = 0.23; I2: 42%), and major bleeding (overall OR = 1.25, 95%CI: 0.58-2.71; P = 0.56; I2: 0%) between the two procedures. These differences remained statistically non-significant in all sensitivity analyses. CONCLUSION: POEM was effective in treating achalasia. Shorter and longer myotomy procedures provided similar therapeutic effects in terms of long-term effectiveness. In addition, shorter myotomy reduced the operative time.

Helicobacter pylori eradication: Exploring its impacts on the gastric mucosa.

Helicobacter pylori (H. pylori) infects approximately 50% of all humans globally. Persistent H. pylori infection causes multiple gastric and extragastric diseases, indicating the importance of early diagnosis and timely treatment. H. pylori eradication produces dramatic changes in the gastric mucosa, resulting in restored function. Consequently, to better understand the importance of H. pylori eradication and clarify the subsequent recovery of gastric mucosal functions after eradication, we summarize histological, endoscopic, and gastric microbiota changes to assess the therapeutic effects on the gastric mucosa.

Comparison of regional and local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis.

BACKGROUND: Arteriovenous fistulae (AVF) are the hemodialysis access modality of choice for patients with end-stage renal disease. However, they have a high early failure rate. Good vascular access is essential to manage long-term hemodialytic treatment, but some anesthesia techniques directly affect venous diameter as well as intra- and post-operative blood flow. The main purpose of this meta-analysis was to compare the results of regional and local anesthesia (RA and LA) for arteriovenous fistula creation in end-stage renal disease. METHODS: We conducted a systematic review and meta-analysis to synthesize evidence from 7 randomized controlled trials (565 patients) and 1 observational study (408 patients) with the aim of evaluating the safety and efficacy of RA versus LA in surgical construction of AVF. RESULTS: Pooled data showed that RA was associated with higher primary patency rates than LA (odds ratio [OR], 1.88; 95% confidence interval [CI]: 1.24-2.84; P = 0.003; I2 = 31%). Additionally, brachial artery diameter was significantly increased in the RA versus LA group (mean difference [MD], 0.83; 95% CI: 0.75-0.92; P < 0.001; I2 = 97%) and the need for intra- as well as post-operative pain killers was significantly less (RA, P = 0.0363; LA, P = 0.0318). Moreover, operation duration was significantly reduced using RA versus LA (MD, - 29.63; 95% CI: - 32.78 - -26.48; P < 0.001; I2 = 100%). CONCLUSIONS: This meta-analysis suggests that RA is preferable to LA in patients with end-stage renal disease in guaranteeing AVF patency and increasing brachial artery diameter.

Renal sympathetic denervation lowers arterial pressure in canines with obesity-induced hypertension by regulating GAD65 and AT1R expression in rostral ventrolateral medulla.

To explore the roles of glutamate acid decarboxylase 65 (GAD65) and angiotensin II type 1 receptor (AT1R) in the action of renal sympathetic denervation (RSD) on obesity-induced hypertension in canines. Thirty-two beagles were randomly divided into a hypertensive model (n = 22) and control (n = 10) groups. A hypertensive canine model was established by feeding a high-fat diet. Twenty hypertensive beagles were randomized equally to a sham-surgery and RSD-treated group receiving catheter-based radiofrequency RSD. Compared with the control group, the sham-surgery group exhibited significant increases in blood pressure, serum angiotensin II level, rostral ventrolateral medulla (RVLM) glutamate level, and AT1R mRNA and protein expression and decreases in γ-amino acid butyric acid (γ-GABA) level and GAD65 mRNA and protein expression in the RVLM (all P < 0.05). Treatment with RSD significantly attenuated the above abnormal alterations (all P < 0.05). Linear correlation analysis revealed that angiotensin II level was positively correlated with glutamate level (r = 0.804) and inversely correlated with γ-GABA level (r = -0.765). GAD65 protein expression was positively correlated with γ-GABA level (r = 0.782). Catheter-based radiofrequency RSD can decrease blood pressure in obesity-induced hypertensive canines. The antihypertensive mechanism might be linked to upregulation of GAD65 and downregulation of AT1R in the RVLM.

Effects of chemerin/CMKLR1 in obesity-induced hypertension and potential mechanism.

BACKGROUND: Obesity-induced hypertension (OIH) has a high morbidity and mortality, and its prevention and treatment has been a major challenge in clinical practice. Chemerin is a newly discovered adipokine closely related to OIH. METHODS: Male Wistar rats (8W) were divided into either a high-fat diet or a regular diet group. Body weight and blood pressure were measured every two weeks. After 20 weeks, serum, adipose tissue and aortic arteries were collected. Arterial tensions were detected; Immunohistochemistry, ELISA and Western blotting were used to detect the expression of chemerin, CMKLR1, Rock2 and P-MYPT1 in the aorta and perivascular adipose tissues. RESULTS: After 4 weeks, the body weight, systolic blood pressure, diastolic blood pressure and mean arterial pressure were all significantly higher in the high-fat diet group (P<0.05). There was no significant difference in serum chemerin concentration between the OIH group and the control group. However, chemerin and CMKLR1 protein expression was higher in aortic arteries and perivascular adipose tissues of the OIH group (P<0.05). The arterial tension induced by chemerin 9 (1 µM) and the expression of Rock2 and P-MYPT1 were higher in the OIH group (P<0.05). CONCLUSION: OIH positively correlated with chemerin in tissues but not serum. Arterial tension was increased by chemerin 9. Rock2/P-MYPT1 might be involved in the pathogenesis of increased vascular tone in OIH rats.

Effects and Mechanisms of Radiofrequency Ablation of Renal Sympathetic Nerve on Anti-Hypertension in Canine.

BACKGROUND: Radiofrequency ablation of renal sympathetic nerve (RDN) shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. OBJECTIVE: We hypothesized that abnormal levels of norepinephrine (NE) and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2), angiotensin (Ang)-(1-7) and Mas receptor mediate the anti-hypertensive effects of RDN. METHODS: Mean values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE) concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7)- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet. RESULTS: RDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH) expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT) were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7) and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group. CONCLUSION: RDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7)-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.

Effects and Mechanisms of Radiofrequency Ablation of Renal Sympathetic Nerve on Anti-Hypertension in Canine / Efeitos e Mecanismos da Denervação Simpática Renal por Radiofrequência na Anti-Hipertensão em Cães

Abstract Background: Radiofrequency ablation of renal sympathetic nerve (RDN) shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. Objective: We hypothesized that abnormal levels of norepinephrine (NE) and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2), angiotensin (Ang)-(1-7) and Mas receptor mediate the anti-hypertensive effects of RDN. Methods: Mean values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE) concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7)- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet. Results: RDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH) expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT) were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7) and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group. Conclusion: RDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7)-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.

Resumo Fundamentos: A denervação simpática renal por radiofrequência (DSR) mostra redução eficaz da pressão arterial (PA) de pacientes hipertensos, ainda que os mecanismos específicos permaneçam obscuros. Objetivo: Fizemos a hipótese de que níveis alterados de noradrenalina (NA) e mudanças nas enzimas relacionadas à NA e enzima conversora de angiotensina 2 (ECA-2), angiotensina (Ang)-(1-7) e receptor Mas são mediadores dos efeitos antihipertensivos da DSR. Métodos: Foram avaliados os valores médios de pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e pressão arterial média (PAM) no início e durante o seguimento. Foram medidas as concentrações plasmática e renal de noradrenalina (NA) por cromatografia líquida de alta eficiência com detecção eletroquímica, e os níveis de enzima relacionada à NA e ECA2-Ang-(1-7)-Mas através de PCR em tempo real, Western blot e imunohistoquímica ou Elisa em um modelo canino de hipertensão que recebeu ração rica em gordura e foi tratado com DSR. Os parâmetros também foram determinados em um grupo de cirurgia simulada submetido à arteriografia renal e em um grupo controle que recebeu dieta normal. Resultados: DSR causou diminuição da PAS, PAD, PAM e das concentrações plasmática e renal de NA. Em comparação ao grupo placebo, a expressão da tirosina hidroxilase (TH) renal foi menor e a da renalase foi maior no grupo DSR. Em comparação ao grupo controle, os níveis de TH renal e de catecol-o-metil-transferase (COMT) foram maiores e os de renalase foram menores no grupo cirurgia simulada. Além disso, os níveis renais de ECA2, Ang-(1-7) e Mas foram maiores no grupo DSR do que no grupo cirurgia simulada, que, por sua vez, foram menores do que no grupo controle. Conclusões: A DSR mostra efeitos anti-hipertensivos com redução da NA e ativação da ECA2-Ang-(1-7)-Mas, o que indica que pode contribuir com o efeito anti-hipertensivo da DSR.

[Carotid intima-media thickness and estimated glomerular filtration rate in hypertensive patients].

OBJECTIVE: To determine the association between carotid atherosclerosis and renal function in hypertensive patients. METHODS: A total of 2 809 hypertensive patients aged (56.59±10.79) years were enrolled. Carotid intima-media thickness (cIMT) was derived via B-mode ultrasonography and chronic kidney disease (CKD) was evaluated by the estimated glomerular filtration rate (eGFR) with Cockcroft- Gault method. The patients were divided into 3 groups: a normal group, a thick group, and a plaque group according to the results of carotid ultrasonography. RESULTS: The eGFR of the normal group was (111.09±25.61) mL/(min.1.73m(2)), that of the thick group and the plaque group was (94.45±27.14) mL/(min.1.73m(2)) and (85.98±26.92) mL/ (min.1.73m(2)). Binary logistic analysis showed that age (OR=3.590), smoking status (OR=1.543), systolic blood pressure (OR=1.018), diastolic blood pressure (OR=0.977), fasting plasma glucose (OR=1.132), triglyceride (OR=0.873) and eGFR (OR=0.986) were significantly correlated with cIMT. Subgroup analyses on different genders showed that eGFR was a significant independent risk factor in men (OR=0.991) but not in women. CONCLUSION: The thicker the cIMT, the lower the eGFR in hypertensive patients. With the development of cIMT, eGFR gradually decreases and contributes to the occurrence and development of early-stage atherosclerosis in hypertensive patients.

Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.

The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity.