Increased urinary adiponectin level is associated with contrast-induced nephropathy in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Contrast-induced nephropathy (CIN) is one of major and serious complications in patients undergoing percutaneous coronary intervention (PCI). It is unknown whether increased urinary adiponectin (UAPN), a sensitive marker for early renal function impairment, is associated with an increased risk of CIN. Therefore, we prospectively investigate the association of UAPN with CIN. METHODS: We prospectively enrolled 208 patients who were undergoing elective PCI. The baseline UAPN was assessed prior to PCI. The ROC analysis was used to evaluate the predictive value of UAPN for CIN. Multivariate logistic regression analysis was performed to analyze the independent risk factors for CIN. RESULTS: Of 208 patients, CIN occurred in 19 patients (9.13%), and 6 of them (2.88%) required dialysis. Patients with CIN had a higher UAPN level than those without CIN (17.15 ± 12.36 vs. 10.29 ± 3.04 ng/ml, P < 0.01). ROC analysis showed that the optimal cutoff value of UAPN for predicting CIN was 12.24 ng/ml with 68.42% sensitivity and 76.72% specificity (AUC = 0.7204; 95% CI, 0.582-0.859; 푃< 0.01). Multivariate analysis demonstrated that UAPN (OR, 5.071; 95% CI,1.711-15.028; P < 0.01) and serum creatinine (Scr) > 124 µmol/L (OR, 4.210; 95% CI, 1.297-13.669; P < 0.01) were independently associated with CIN. CONCLUSIONS: Our present study showed that a higher baseline UAPN (≥12.24 ng/ml) level was significantly associated with an increased risk for developing CIN post PCI.

Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.

Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF.

rs2910164 Polymorphism Confers a Decreased Risk for Pulmonary Hypertension by Compromising the Processing of microRNA-146a.

OBJECTIVE: To identify the association between rs2910164 polymorphism and development of pulmonary hypertension, as well as underlying molecular mechanism. METHODS AND RESULTS: 281 patients diagnosed with pulmonary hypertension and 325 normal controls were recruited, and rs2910164 genotype was determined in each participant: As a result, the rs2910164 polymorphism was significantly associated with the development of pulmonary hypertension after adjusting some potential confounding factors. Additionally, lung tissue samples were obtained from 39 patients who received surgical intervention for lung cancer, and mRNA and protein expression levels of miR-146a, COX-2 and PGI2 production were examined. Furthermore, we confirmed COX-2 is a target of miR-146a in pulmonary smooth muscle cells, and identified a differentially expressed miR-146a and COX-2 in each rs2910164 genotype group. We observed a significant association between rs2910164 polymorphism and the levels of either COX-2 or PGI2 using real-time PCR and western blot. In conclusion, the results of this study demonstrate that the rs2910164 CC and GC genotype is associated with a decreased risk of pulmonary hypertension, which could be attributed to defective miRNA processing and compromised ability to inhibit production of COX-2 and PGI2.

Individualized Blind Techniques for Puncture of Intrathoracic and Extrathoracic Subclavian Vein: Three Simple Experience Tips.

BACKGROUND: Although several procedures of subclavian venipuncture have been reported, no standard method has been established yet. The purpose of this study was to investigate some more accurate and improved blind puncture tips. METHODS: A prospective study was conducted on patients who underwent cardiac radio-frequency ablation with the blind technique of subclavian venipuncture from August 2018 to June 2022. All patients were randomly assigned to an intrathoracic approach group or extrathoracic approach group. Each group of patients followed their own specific puncture scheme and tips. RESULTS: About 371 punctures were included. Blind subclavian venipunctures were performed with 98.9% technical success and without complications in all patients. The over-all success rate with an intrathoracic and extrathoracic approach was equivalent (96.7% vs. 98.3%, P =.23). The intrathoracic group showed a higher first-pass success compared with the extrathoracic group (91.9% vs. 80.2%, P = 0.003, respectively). CONCLUSION: We localized the landmark/reference and skin puncture site of an intrathoracic and extrathoracic subclavian venipuncture individually and quantitatively. These experiences make blind techniques more accurate and faster.

Clinical Significance of the D-Loop Gene Mutation in Mitochondrial DNA in Laryngeal Cancer.

OBJECTIVE: The aim of the present study was to investigate the D-loop gene mutation and microsatellite instability in the mitochondrial DNA (mtDNA) and the correlation with the clinical and pathological parameters in laryngeal cancer. METHODS: The tumor tissues and paratumor tissues in 60 cases of laryngeal cancer were selected, and DNA was extracted from these tissues. The D-loop region in mtDNA was amplified by PCR with the gene sequence of the amplified product being detected. The gene sequence of the detected region was compared with the revised Cambridge Reference Sequence (rCRS) and the related database by using the Mitomaster software. The correlation between the D-loop gene mutation and the clinical and pathological parameters was investigated. RESULTS: A total of 174 mutations across 38 sites were detected in 51 (85%) of samples. Most of the mutations were concentrated in the high various (HV) I region, and the main types of mutations were the substitution of a single base or insertion and deletion of a single base. There was also microsatellite instability in the D310 region. The statistical results showed that there was no correlation between the age, gender, tumor diameter, and TNM stage, and the number of the D-loop mutations in mtDNA (P > 0.05). CONCLUSION: There existed high-frequency mutation of the D-loop gene in mtDNA in laryngeal cancer, which might play an important role in the pathogenesis of laryngeal cancer.

Branched chain amino acids exacerbate myocardial ischemia/reperfusion vulnerability via enhancing GCN2/ATF6/PPAR-α pathway-dependent fatty acid oxidation.

Rationale: Myocardial vulnerability to ischemia/reperfusion (I/R) injury is strictly regulated by energy substrate metabolism. Branched chain amino acids (BCAA), consisting of valine, leucine and isoleucine, are a group of essential amino acids that are highly oxidized in the heart. Elevated levels of BCAA have been implicated in the development of cardiovascular diseases; however, the role of BCAA in I/R process is not fully understood. The present study aims to determine how BCAA influence myocardial energy substrate metabolism and to further clarify the pathophysiological significance during cardiac I/R injury. Methods: Parameters of glucose and fatty acid metabolism were measured by seahorse metabolic flux analyzer in adult mouse cardiac myocytes with or without BCAA incubation. Chronic accumulation of BCAA was induced in mice receiving oral BCAA administration. A genetic mouse model with defective BCAA catabolism was also utilized. Mice were subjected to MI/R and the injury was assessed extensively at the whole-heart, cardiomyocyte, and molecular levels. Results: We confirmed that chronic accumulation of BCAA enhanced glycolysis and fatty acid oxidation (FAO) but suppressed glucose oxidation in adult mouse ventricular cardiomyocytes. Oral gavage of BCAA enhanced FAO in cardiac tissues, exacerbated lipid peroxidation toxicity and worsened myocardial vulnerability to I/R injury. Etomoxir, a specific inhibitor of FAO, rescued the deleterious effects of BCAA on I/R injury. Mechanistically, valine, leucine and their corresponding branched chain α-keto acid (BCKA) derivatives, but not isoleucine and its BCKA derivative, transcriptionally upregulated peroxisome proliferation-activated receptor alpha (PPAR-α). BCAA/BCKA induced PPAR-α upregulation through the general control nonderepresible-2 (GCN2)/ activating transcription factor-6 (ATF6) pathway. Finally, in a genetic mouse model with BCAA catabolic defects, chronic accumulation of BCAA increased FAO in myocardial tissues and sensitized the heart to I/R injury, which could be reversed by adenovirus-mediated PPAR-α silencing. Conclusions: We identify BCAA as an important nutrition regulator of myocardial fatty acid metabolism through transcriptional upregulation of PPAR-α. Chronic accumulation of BCAA, caused by either dietary or genetic factors, renders the heart vulnerable to I/R injury via exacerbating lipid peroxidation toxicity. These data support the notion that BCAA lowering methods might be potentially effective cardioprotective strategies, especially among patients with diseases characterized by elevated levels of BCAA, such as obesity and diabetes.

Involvement of activated astrocyte and microglia of locus coeruleus in cardiac pain processing after acute cardiac injury.

OBJECTIVE: It is still not known whether the glial cell activation of locus coeruleus (LC) is involved in the neurophysiologic mechanism of the acute phase of heart disease. The aim of this study was to investigate whether the glial cell activation of LC responds to acute cardiac injury (ACI). METHODS: In this study, ACI was established by intramyocardial injection of formalin. Afterward, we analysed c-Fos, OX42, GFAP and P2X(4)R expression levels in the LC of the rats by immunofluorescence staining or Western blot analysis. RESULTS: There was no significant difference in the levels of these markers in the LC between the normal control and the sham-operated groups. Following ACI, up-regulation of GFAP, OX42 and P2X(4)R expression levels were observed in locus coeruleus of the rats. The peak expression time was at hour 24. P2X(4)R was colocalized with OX42 in activated microglias, but not with GFAP in activated astrocytes. Compared with the control group, the ACI group showed a high expression level of c-Fos at hour 1 with a peak expression level at hour 2. CONCLUSION: The results showed that LC glia cells, like neurons, could sensitively respond to cardiovascular nociception induced by ACI at different time points. Results of this study may provide insights into the role of glial activation in response to ACI and may represent a potential strategy for investigation of neurophysiologic mechanism of cardiac pain.

Left main bronchus as a guide for individualized transseptal puncture using a conventional fluoroscopic approach in cryoballoon ablation of atrial fibrillation.

OBJECTIVE: Although imaging modalities, such as transesophageal and intracardiac echocardiography, have helped to improve the safety of atrial transseptal puncture (TSP), fluoroscopy is still traditionally and widely used in TSP. The aim of the present study was to evaluate an individual knack for TSP during cryoballoon ablation of atrial fibrillation (AF) under fluoroscopy. METHODS: Through the prospective study of 72 cases of patients with paroxysmal or persistent AF admitted for cryoablation in our center, 46 cases using a puncture site toward the bifurcation of the left main bronchus (LMB group) and 26 cases using an anterior-inferior puncture site (AI group) were included in the study. The acute pulmonary vein (PV) isolation success rate, single-procedure success rate, and time-to-effect (TTE) between the two groups were analyzed. RESULTS: All PVs were identified and successfully isolated, and there are no differences in the two groups. However, the mean TTE was shorter in the LMB group than in the AI group. Moreover, a higher single-procedure success rate was observed in the LMB group. CONCLUSION: The bifurcation of the LMB can be clearly evaluated in each patient under fluoroscopy and is an anatomical landmark for the location of the left PV. TSP guided by the LMB is a new practical method for choosing individualized transseptal sites for catheter ablation of AF, which can help to shorten TTE and procedure time.

Circular RNA expression profiles of persistent atrial fibrillation in patients with rheumatic heart disease.

OBJECTIVE: To investigate the expression profile of circular RNAs (circRNAs) and proposed circRNA-microRNA (miRNA) regulatory network in atrial fibrillation (AF). METHODS: Atrial tissues from patients with persistent AF with rheumatic heart disease and non-AF myocardium with normal hearts were collected for circRNA differential expression analyses by high-throughput sequencing. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the differentially expressed genes and AF-related pathways. Co-expression networks of circRNA-miRNA were constructed based on the correlation analyses between the differentially expressed RNAs. Quantitative reverse transcription polymerase chain reaction (PCR) was performed to validate the results. RESULTS: A total of 108 circRNAs were found to be differentially expressed in AF. Among them, 51 were up-regulated, and 57 were down-regulated. Dysregulated circRNAs were validated by quantitative real-time PCR. The GO and KEGG pathway enrichment analyses were executed to determine the principal functions of the significantly deregulated genes. Furthermore, we constructed correlated expression networks between circRNAs and miRNAs. circRNA19591, circRNA19596, and circRNA16175 interacted with 36, 28, and 18 miRNAs, respectively; miR-29b-1-5p and miR-29b-2-5p were related to 12 down-regulated circRNAs, respectively. CONCLUSION: Our findings provide a novel perspective on circRNAs involved in AF due to rheumatic heart disease and establish the foundation for future research of the potential roles of circRNAs in AF.

[Effects of constant magnetic fields on proliferation and migration of endothelial progenitor cells under rapamycin intervention: experiment with rats].

OBJECTIVE: To investigate the effects of constant magnetic field (CMF) on proliferation and migration of bone marrow-derived endothelial progenitor cells (EPCs) under rapamycin intervention. METHODS: EPCs were isolated from rat bone marrow by density gradient centrifugation and cultured on fibronectin-coated dishes. Six days later the attached cells were divided into 5 groups: control group, rapamycin (1 ng/ml) group, and 3 rapamycin + CMF groups (treated with CMF of the doses 0.1 mT, 0.5 mT, and 1.0 mT respectively). Samples were collected 24 hours after incubation. Cell proliferation was measured by MTT chromatometre. EPC migration was detected with modified Boyden chamber assay. RESULTS: The EPC proliferation ability of the rapamycin group, expressed by absorbance, was (0.252 +/- 0.006), significantly lower than that of the control group [(0.328 +/- 0.025), P < 0.05]. The number of migrating EPC was (31 +/- 3) cells, significantly lower than that of the control group [(48 +/- 5), P < 0.05]. The EPC proliferation ability of the rapamycin + CMF 0.5 mT and 1.0 mT groups, expressed by absorbance, were (0.278 +/- 0.008) and (0.280 +/- 0.010) respectively, both significantly higher than that of the control group (both P < 0.05). The migrating EPC number of the rapamycin + CMF 0.5 mT and 1.0 mT groups were (37 +/- 3) and (38 +/- 4) respectively, both significantly higher than that of the control group (both P < 0.05). CONCLUSION: CMF of the doses of 0.5 mT and 1.0 mT antagonizes the effects of rapamycin on EPCs, increasing the proliferation and migration of EPCs.

Impaired adiponectin signaling contributes to disturbed catabolism of branched-chain amino acids in diabetic mice.

The branched-chain amino acids (BCAA) accumulated in type 2 diabetes are independent contributors to insulin resistance. The activity of branched-chain α-keto acid dehydrogenase (BCKD) complex, rate-limiting enzyme in BCAA catabolism, is reduced in diabetic states, which contributes to elevated BCAA concentrations. However, the mechanisms underlying decreased BCKD activity remain poorly understood. Here, we demonstrate that mitochondrial phosphatase 2C (PP2Cm), a newly identified BCKD phosphatase that increases BCKD activity, was significantly downregulated in ob/ob and type 2 diabetic mice. Interestingly, in adiponectin (APN) knockout (APN(-/-)) mice fed with a high-fat diet (HD), PP2Cm expression and BCKD activity were significantly decreased, whereas BCKD kinase (BDK), which inhibits BCKD activity, was markedly increased. Concurrently, plasma BCAA and branched-chain α-keto acids (BCKA) were significantly elevated. APN treatment markedly reverted PP2Cm, BDK, BCKD activity, and BCAA and BCKA levels in HD-fed APN(-/-) and diabetic animals. Additionally, increased BCKD activity caused by APN administration was partially but significantly inhibited in PP2Cm knockout mice. Finally, APN-mediated upregulation of PP2Cm expression and BCKD activity were abolished when AMPK was inhibited. Collectively, we have provided the first direct evidence that APN is a novel regulator of PP2Cm and systematic BCAA levels, suggesting that targeting APN may be a pharmacological approach to ameliorating BCAA catabolism in the diabetic state.

Extranodal follicular dendritic cell sarcoma of the soft palate: a case report.

Follicular dentritic cell sarcoma (FDCS) is an extremely rare malignant neoplasm arising from the accessory cells of the lymph nodes, the follicular dendritic cells. They commonly occur in the lymph nodes, but have also been reported at extranodal sites. Because of its rarity, FDCS is not easily to make a diagnosis by clinicians or pathologists. Herein, we report a soft palate tumor in a 59-year-old female, with a history of tonsillectomy. Pharynx MRI scan revealed a 4.7×3.0×3.5 cm mass at the right side of the parapharyngeal space. The pathology results returned as Follicular dentritic cell sarcoma. The patient underwent a tumorectomy and adjuvant postoperative radiotherapy. The patient was free of disease 1 year after the end of the treatment. The FDCS is an infrequent nonlymphoid malignant tumor accounting for less than 1% of all head and neck tumors. The immunohistochemical technique is essential for accurately identifying this class of tumour.

[Follicular dendritic cell sarcoma of soft plate: one case report].

Follicular dendritic cell sarcoma is a rare low-grade malignant tumor. At present, only twenty ca ses was discovered all over the world. This paper reports a case treated in our hospital, explores the clinical manifestations, pathological diagnosis and treatment to provide certain help to clinical doctor in diagnosis and treatment to reduce the misdiagnosis of the disease.

Effect of chronic pretreatment of angiotensin-converting receptor blocker on no-reflow phenomenon in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

AIMS: Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction. METHODS: We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade <3, which was determined by the TIMI frame count method using angiographic images obtained just after PCI and stenting. RESULTS: Compared with patients without ARB treatment, patients with ARB had more frequently hypertension and ST resolution (P < 0.05), but no significant difference was found in the other clinical characteristics (age, sex, Hyperlipidaemia, Diabetes mellitus, etc) between the two groups. A total of 51 patients receiving chronic ARB treatment before admission have lower incidence of the no-reflow phenomenon than those without chronic ARB treatment (8.7% and 26.7%, P= 0.003). However, the incidence of the no-reflow phenomenon between the patients with and without hypertension had no significant difference. Multivariable logistic regression analysis revealed that ARB pretreatment was a significant predictor of the no-reflow phenomenon, whereas blood pressure was found to be insignificant. CONCLUSION: Chronic pretreatment of ARB is associated with the reduction of the no-reflow phenomenon in patients with reperfused AMI and could preserve microvascular integrity after AMI independent of blood pressure lowering, which may contribute to better functional recovery.

Exposure of aortic vascular smooth muscle cells to low-frequency electromagnetic field inhibits osteopontin expression and matrix metalloproteinase activity.

Primary cultured rat aortic vascular smooth muscle cells (VSMCs) were exposed to different intensities of low-frequency electromagnetic fields (LFEMFs) at 20, 40, and 60 mT for different time periods (10, 20, and 30 minutes). Furthermore, osteopontin (OPN) mRNA and protein expressions were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Matrix metalloproteinase-2 (MMP-2) activity was measured using gelatin zymography. The results showed that the OPN mRNA and protein expressions and MMP-2 activity of VSMCs were inhibited by exposure to LFEMFs of different intensities in a dose-dependent manner (P < 0.05) but not in a time-dependent manner. In conclusion, exposure to LFEMFs of appropriate intensity for a suitable time period can result in the inhibition of the OPN expression and MMP-2 activity of VSMCs, indicating the potential prophylactic and therapeutic effects of LFEMFs on restenosis (RS) following percutaneous coronary intervention (PCI).

The opposite-direction modulation of CD4+CD25+ Tregs and T helper 1 cells in acute coronary syndromes.

Different subsets of T lymphocytes have different functions in atherosclerosis advancement. T helper 1 cells and T regulatory 1 cells have been demonstrated to play opposite roles in rupture of atherosclerotic lesion. However, the role of novel subset of T regulatory cells, known as CD4+CD25+Foxp3+ T cells, remains largely unknown in coronary artery disease (CAD). In this study, we investigated the peripheral CD4+CD25+Foxp3+ T cells of patients with CAD and controls. The patients submitted were divided into three groups: stable angina pectoris (SA) group, unstable angina pectoris (UA) group and acute myocardial infarction (AMI) group. We analyzed the frequencies of peripheral CD4+CD25+Foxp3+ T cells and T helper 1/T helper 2 cells, expression of Foxp3 in CD4+CD25+ T subsets and cytokines pattern in patients and controls. We found that the reduction of CD4+CD25+Foxp3+ T lymphocytes was consistent with the expansion of Th1 cells in patients with unstable CAD. The reversed development between CD4+CD25+ Tregs and Th1 cells might contribute to plaque destabilization.