Hydrostatic pressure stimulates the osteogenesis and angiogenesis of MSCs/HUVECs co-culture on porous PLGA scaffolds.

In native bone tissue regeneration, blood vessels, providing oxygen and nutrition for tissues, can promote the regeneration of bone and accelerate the repair of a defected area. In this study, Poly(D, L-lactic-co-glycolic acid) (PLGA) inverse opal scaffolds with high pore interconnectivity were fabricated and further modified with vascular endothelial growth factor (VEGF). The rat bone marrow derived mesenchymal stem cells (rMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured onto the scaffolds to enhance vascularization for bone tissue regeneration. Cell attachment, viability, proliferation, and morphology were detected by cell counting kit-8 (CCK-8) assay, live and dead staining and scanning electron microscopy (SEM). Hydrostatic pressure with 0-279 KPa and 1 Hz one hour per day for 7 days was applied to tissue engineered bone constructs to investigate whether the loading stimulation can promote osteogenesis and angiogenesis mutually evaluated in parallel by multiple in vitro assays and in an in vivo chicken chorioallantoic membrane (CAM) model. The results indicated that the immobilization of VEGF can improve biocompatibility of PLGA scaffolds and promote cell attachment and proliferation. The cell-scaffold constructs showed higher CD31 expression because of the angiogenic differentiation of rMSCs in hydrostatic loading culture condition in vitro. The in vivo CAM model experiment demonstrated that hydrostatic loading stimulated angiogenic differentiation of rMSCs can accelerate tubulogenesis. Furthermore, the new capillaries formed in cell-scaffold constructs were conducive to calcium deposition in vivo.

Blood lead level in Chinese adults with and without coronary artery disease.

BACKGROUND: The Trial to Assess Chelation Therapy study found that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced the incidence of cardiac events in stable post-myocardial infarction patients, and a body of epidemiological data has shown that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. However, limited studies have focused on the relationship between angiographically diagnosed coronary artery disease (CAD) and lead exposure. This study compared blood lead level (BLL) in Chinese patients with and without CAD. METHODS: In this prospective, observational study, 450 consecutive patients admitted to Beijing Anzhen Hospital with suspected CAD from November 1, 2018, to January 30, 2019, were enrolled. All patients underwent coronary angiography, and an experienced heart team calculated the SYNTAX scores (SXscore) for all available coronary angiograms. BLLs were determined with atomic absorption spectrophotometry and compared between patients with angiographically diagnosed CAD and those without CAD. RESULTS: In total, 343 (76%) patients had CAD, of whom 42% had low (0-22), 22% had intermediate (23-32), and 36% had high (≥ 33) SXscore. BLLs were 36.8 ± 16.95 µg/L in patients with CAD and 31.2 ± 15.75 µg/L in those without CAD (P = 0.003). When BLLs were categorized into three groups (low, middle, high), CAD prevalence increased with increasing BLLs (P < 0.05). In the multivariate regression model, BLLs were associated with CAD (odds ratio (OR): 1.023, 95% confidence interval (CI): 1.008-1.039; P = 0.0017). OR in the high versus low BLL group was 2.36 (95% CI: 1.29-4.42,P = 0.003). Furthermore, BLLs were independently associated with intermediate and high SXscore (adjusted OR: 1.050, 95% CI: 1.036-1.066; P < 0.0001). CONCLUSION: BLLs were significantly associated with angiographically diagnosed CAD. Furthermore, BLLs showed excellent predictive value for SXscore, especially for complex coronary artery lesions.

Balloon internal fixation: A novel approach to manipulate catheter knotting.

A successful alternative technique to resolve the catheter knotting during radial access using balloon internal fixation of 5F angiographic catheter in the cath laboratory.

Atorvastatin Pretreatment Ameliorates Mesenchymal Stem Cell Migration through miR-146a/CXCR4 Signaling.

BACKGROUND: We previously found that atorvastatin (ATV) enhanced mesenchymal stem cells (MSCs) migration, by a yet unknown mechanism. CXC chemokine receptor 4 (CXCR4) is critical to cell migration and regulated by microRNA-146a (miR-146a). Therefore, this study aimed to assess whether ATV ameliorates MSCs migration through miR-146a/CXCR4 signaling. METHODS: Expression of CXCR4 was evaluated by flow cytometry. Expression of miR-146a was examined by reverse transcription-quantitative polymerase chain reaction. A transwell system was used to assess the migration ability of MSCs. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague-Dawley rats with acute myocardial infarction (AMI). Mimics of miR-146a were used in vitro, and miR-146a overexpression lentivirus was used in vivo, to assess the role of miR-146a in the migration ability of MSCs. RESULTS: The results showed that ATV pretreatment in vitro upregulated CXCR4 and induced MSCs migration. In addition, flow cytometry demonstrated that miR-146a mimics suppressed CXCR4, and ATV pretreatment no longer ameliorated MSCs migration because of decreased CXCR4. In the AMI model, miR-146a-overexpressing MSCs increased infarct size and fibrosis. CONCLUSION: The miR-146a/CXCR4 signaling pathway contributes to MSCs migration and homing induced by ATV pretreatment. miR-146a may be a novel therapeutic target for stimulating MSCs migration to the ischemic tissue for improved repair.

Comparing hydroxyapatite with osteogenic medium for the osteogenic differentiation of mesenchymal stem cells on PHBV nanofibrous scaffolds.

Having advantageous biocompatibility and osteoconductive properties known to enhance the osteogenic differentiation of mesenchymal stem cells (MSCs), hydroxyapatite (HA) is a commonly used material for bone tissue engineering. What remains unclear, however, is whether HA holds a similar potential for stimulating the osteogenic differentiation of MSCs to that of a more frequently used osteogenic-inducing medium (OIM). To that end, we used PHBV electrospun nanofibrous scaffolds to directly compare the osteogenic capacities of HA with OIM over MSCs. Through the observation of cellular morphology, the staining of osteogenic markers, and the quantitative measuring of osteogenic-related genes, as well as microRNA analyses, we not only found that HA was as capable as OIM for differentiating MSCs down an osteogenic lineage; albeit, at a significantly slower rate, but also that numerous microRNAs are involved in the osteogenic differentiation of MSCs through multiple pathways involving the inhibition of cellular proliferation and stemness, chondrogenesis and adipogenesis, and the active promotion of osteogenesis. Taken together, we have shown for the first time that PHBV electrospun nanofibrous scaffolds combined with HA have a similar osteogenic-inducing potential as OIM and may therefore be used as a viable replacement for OIM for alternative in vivo-mimicking bone tissue engineering applications.

Involvement of IL-17 in Secondary Brain Injury After a Traumatic Brain Injury in Rats.

The pro-inflammatory activity of interleukin 17, which is produced by the IL-23/IL-17 axis, has been associated with the pathogenesis of traumatic brain injury (TBI). The study investigated the potential role of IL-17 in secondary brain injury of TBI in a rat model. Our data showed that the levels of IL-17 increased from 6 h to 7 days and peaked at 3 days, in both the CNS and serum, which were consistent with the severity of secondary brain injury. The IL-23 inhibitor suberoylanilide hydroxamic acid (SAHA) treatment markedly decreased the expressions of IL-17 and apoptosis-associated proteins cleaved caspase-3 and increased the protein ratio of Bcl-2 (B cell lymphoma/leukemia-2)/Bax (Bcl-2-associated X protein). Meanwhile, neuronal apoptosis was reduced, and neural function was improved after SAHA treatment. This study suggests that IL-17 is involved in secondary brain injury after TBI. Administering an IL-23 inhibitor and thereby blocking the IL-23/IL-17 axis may be beneficial in the treatment of TBI.

In Vitro Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells by Cerebrospinal Fluid Improves Motor Function of Middle Cerebral Artery Occlusion Rats.

Bone marrow mesenchymal stem cells (BMSCs) represent a promising tool for stem cell-based therapies. However, the majority of BMSC transplants only allow for limited recovery of the lost functions. We previously found that human cerebrospinal fluid (hCSF) is more potent than growth factors in differentiating human BMSCs into neuron-like cells in vitro. In this study, we studied the effect of transplantation of rat BMSC-derived neuron-like cells (BMSC-Ns) induced by hCSF into rat brain with middle cerebral artery occlusion (MCAO). The survival and differentiation of the transplanted cells were determined using immunofluorescence staining of bromodeoxyuridine. The recovery of neurological function were observed by the modified neurological severity score (modified NSS) at 4, 15, and 32 days after cell transplantation, HE staining for determination of the infarct volume at day 32 after cell transplantation. Transplantation of BMSC-Ns or BMSCs significantly improved indexes of neurological function and reduced infarct size in rats previously subjected to MCAO compared with those in the control group. Remarkably, 32 days after transplantation, rats treated with BMSC-Ns presented a smaller infarct size, higher number of neuron-specific, enolase-positive, and BrdU-positive cells, and improved neurological function compared with BMSC group. Our results demonstrate that transplantation of hCSF-treated BMSC-Ns significantly improves neurological function and reduces infarct size in rats subjected to MCAO. This study may pave a new avenue for the treatment of MCAO.

S-Nitrosylation of proline-rich tyrosine kinase 2 involves its activation induced by oxygen-glucose deprivation.

Previous studies have demonstrated that activation of proline-rich tyrosine kinase 2 (PYK2) in cerebral ischemia is involved in the modulation of N-methyl-d-aspartate-type (NMDA) glutamate receptor activity and Ca(2+) dynamics, resulting in ischemic neuron death ultimately. A number of reports indicate that PYK2 is a redox sensitive kinase that must be activated by an estrogen-induced reactive oxygen species (ROS). However, the mechanism of PYK2 activation remains incompletely illustrated. Accumulating attention is focused on nitric oxide (NO, a free radical) which plays a critical role in cellular signal transduction through stimulus-coupled S-nitrosylation of cysteine residues. Here we reported that PYK2 over-expressed in human embryonic kidney (HEK293) cells was S-nitrosylated (forming SNO-PYK2) by reacting with GSNO, an exogenous NO donor, at one critical cysteine residue (Cys534) with a biotin switch assay. Moreover, our results showed that S-nitrosylation and phosphorylation of PYK2 over-expressed in SH-SY5Y cells was significantly increased after oxygen-glucose deprivation (OGD). We further investigated whether the activation (phosphorylation) of PYK2 was associated with S-nitrosylation following SH-SY5Y cells OGD. Our results showed that the cysteine534 residue (site of S-nitrosylation) mutant PYK2 over-expressed in SH-SY5Y cells diminished S-nitrosylation of PYK2 and inhibited its phosphorylation induced by OGD. In addition, overexpression of the mutant PYK2 protein could prevent nuclear accumulation and abrogate neuronal cell death compared to wild type PYK2 in SH-SY5Y cells induced by OGD. These data suggest that the activation of PYK2 following OGD may be modulated by S-nitrosylation, which provides a new avenue for stroke therapy by targeting the post-translational modification machinery.

An early warning scoring system for the prevention of acute heart failure.

BACKGROUND: Early prediction and identification of the onset of acute heart failure (AHF) in high-risk patients are of great significance for preemptive treatment and a better prognosis. We sought to find a scoring system to predict the onset of AHF in patients in the acute heart failure unit (AHFU). METHODS: Data for 433 patients at of AHF in the AHFU were analyzed. We recorded sex, age, history of coronary artery disease, hypertension, diabetes, and primary percutaneous coronary intervention. We also reviewed temperature, pulse, SpO2, respiratory rate, urine volume, and emotional state every hour before the onset of AHF. All admission and follow-up data were retrieved from hospital charts. Factors were analyzed using a binary logistic regression model to create the SUPER (SpO2, urine volume, pulse, emotional state, and respiratory rate) scoring model. We divided the scoring system into four levels: low-, intermediate-, high-, and extremely high-risk. Patients fitting the four risk levels were followed up for 6 to 24 months. RESULTS: SpO2, hourly urine volume, pulse, emotional state and respiratory rates were associated with an independent increased risk for the onset of AHF. The SUPER score for the patients in the AHFU predicted the onset of AHF 3.90 ± 1.94 h (1-17 h) earlier. The areas under the ROC curve for the SUPER score and the modified early warning score were 0.811 and 0.662 (p<0.05), indicating that the SUPER score provided a better warning of the AHF. A low-, intermediate-, high-, and very high-risk SUPER predicted the likelihood of AHF at 17.3%, 61.3%, 84.4%, and 94.0%, respectively. The differences in mortality rates between the four levels were statistically significant (p<0.05). CONCLUSIONS: In patients at high risk of AHF, the SUPER scoring system could predict the onset of AHF 2 to 6h earlier. Preemptive treatment according to the SUPER score may prevent or delay AHF occurrence to improve quality of life and reduce mortality.

Serum uric acid and risk of left atrial thrombus in patients with nonvalvular atrial fibrillation.

BACKGROUND: Serum uric acid (SUA) is a simple and independent marker of morbidity and mortality in a variety of cardiovascular diseases. In this study we aimed to investigate SUA and the risk of left atrial (LA) thrombus in patients with nonvalvular atrial fibrillation (AF). METHODS: In this retrospective study, 1359 consecutive patients undergoing transesophageal echocardiography before catheter ablation of AF were enrolled. Sixty-one of the 1359 patients (4.5%) had LA thrombus. RESULTS: SUA levels in patients with LA thrombus were significantly greater (413.5 ± 98.8 µmol/L vs 366.7 ± 94.3 µmol/L; P < 0.001). Hyperuricemia was defined as SUA ≥ 359.8 µmol/L in women and ≥ 445.6 µmol/L in men determined according to receiver operating characteristic curve. The incidence of LA thrombus was significantly greater in patients with hyperuricemia than in those with a normal SUA level in women (12.1% vs 1.9%; P < 0.001) and in men (8.5% vs 2.8%; P < 0.001). Hyperuricemia had a negative predictive value of 98.1% in women and 97.1% in men for identifying LA thrombus. Hyperuricemia was associated with significantly greater risk of LA thrombus among Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke, Vascular Disease, Age 65 to 74 Years, Sex Category (CHA2DS2-VASc) score = 0, 1, and ≥ 2 groups with odds ratios of 7.19, 4.05, and 3.25, respectively. In multivariable analysis, SUA was an independent risk factor of LA thrombus (odds ratio, 1.004; 95% confidence interval, 1.000-1.008; P = 0.028). CONCLUSIONS: Hyperuricemia was a modest risk factor for LA thrombus, which might refine stratification of LA thrombus in patients with nonvalvular AF.

Congenital anomalous coronary sinus ostium.

Congenital anomalous coronary sinus ostium is extremely rare. We describe a case of congenital left atrial coronary sinus ostium in a patient scheduled for ablation for atrial fibrillation. The anomalous coronary sinus ostium was found when contrast was injected during the ablation procedure and was confirmed by cardiac computed tomography.

Omega-3 fatty acids for postoperative atrial fibrillation: alone or in combination with antioxidant vitamins?

BACKGROUND: The effects of omega-3 polyunsaturated fatty acids (PUFA) on the prevention of postoperative atrial fibrillation (POAF) are inconclusive in current studies. Moreover, the most appropriate composition of PUFA to play the protective role is unclear. The aim of this meta-analysis was to ascertain the protective role of PUFA on POAF and the most appropriate composition. METHODS: Studies were identified through PubMed, CENTRAL, EMBASE, reviews and reference lists of relevant papers. The odds ratio (OR) was calculated for POAF. Statistical analyses were performed with Review Manager 5.0. RESULTS: Eleven randomised controlled trials with 3137 patients were included in the analysis. The use of PUFA alone did not reduce the incidence of POAF compared with the control (OR: 0.76; 95% confidence interval [CI]: 0.57-1.03; P=0.08; I(2)=52%). However, combination therapy with PUFA and vitamins C and E reduced the incidence of POAF by 68% (OR: 0.32; 95%CI: 0.17-0.60; P=0.0005; I(2)=38%). Subgroup analysis indicated that the ratio of EPA/DHA 1:2 was effective in preventing POAF (OR: 0.35; 95%CI: 0.24-0.50; P<0.00001; I(2)=0%), while the ratio not 1:2 failed. CONCLUSIONS: Combination therapy with PUFA and vitamins C and E is effective in the prevention of POAF while PUFA alone is not. The ratio of EPA/DHA may influence the incidence of POAF, and 1:2 may be most appropriate. Studies about PUFA on the prevention of POAF are still worthwhile to be conducted in the future.

Predictors of recurrence after a repeat ablation procedure for paroxysmal atrial fibrillation: role of left atrial enlargement.

AIMS: This study sought to explore the predictors of recurrence in patients with paroxysmal atrial fibrillation (AF) undergoing repeat catheter ablation, especially the impact of left atrial (LA) remodelling after the original procedure on the outcome of repeat procedure. METHODS AND RESULTS: Ninety-five patients undergoing repeat ablation were enrolled in this study. Repeat procedure endpoints were pulmonary vein isolation, linear block when linear ablation is performed, and non-inducibility of atrial tachyarrhythmia by burst pacing. Patients with LA enlargement between the pre-original procedure and pre-repeat procedure were categorized as Group 1 (35 patients), while individuals with no change or decrease of LA diameter were categorized as Group 2 (60 patients). The mean duration from the original procedure to the repeat procedure was 12 months (1-40 months). After 29.6 ± 20.5 (3-73) months follow-up from the repeat procedure, 33 patients experienced recurrence (34.7%). The recurrence rate was significantly higher in Group 1 than in Group 2 (51.4 VS. 25.0%, P = 0.017). In univariate analysis, LA remodelling was the only predictor of recurrence. In multivariate analysis, after adjustment for age and LA diameter, Group 1 had a greater risk of recurrence after the repeat procedure (hazard ratio = 2.22, 95% confidence interval: 1.02-4.81, P = 0.043). CONCLUSIONS: Left atrial enlargement after undergoing the original catheter ablation of paroxysmal AF was an independent risk factor of recurrence after repeat ablation.

Pacing or ablation: which is better for paroxysmal atrial fibrillation-related tachycardia-bradycardia syndrome?

BACKGROUND: Symptomatic prolonged sinus pauses on termination of atrial fibrillation (AF) are an accepted indication for pacemaker implantation. We evaluated the outcome of AF ablation in patients with paroxysmal AF-related tachycardia-bradycardia syndrome and compared the efficacy of catheter ablation with permanent pacing plus antiarrhythmic drugs (AADs). METHODS AND RESULTS: Patients with prolonged symptomatic sinus pauses on termination of AF were retrospectively analyzed. Forty-three consecutive patients who underwent catheter ablation (ABL group) were compared to 57 patients who underwent permanent pacing plus AADs (PM group). All 43 patients in the ABL group fulfilled Class I indication for pacemaker implantation at baseline but they actually underwent AF ablation. Reevaluation after 20.1 ± 9.6 months of follow-up showed that 41 patients (95.3%) did no longer need a pacemaker (Class III indication). Total cardiac-related rehospitalization was not significantly different between the two groups (P = 0.921). Tachycardia-related hospitalization was significantly higher in the PM group than the ABL group (14.0% and 0%, P = 0.029). More patients in the PM group were on AADs (PM 40.4%, ABL 4.7%, P < 0.001) while sinus rhythm maintenance was remarkably higher in the ABL group at the end of follow-up (83.7% vs 21.1% in PM group, P < 0.001). CONCLUSIONS: In patients with paroxysmal AF-related tachycardia-bradycardia syndrome, AF ablation seems to be superior to a strategy of pacing plus AAD. Pacemaker implantation can be waived in the majority of patients after a successful ablation.

[Effect of fasudil of on rat cardiomyocytes acutely exposed to omethoate].

OBJECTIVE: To investigate the effect of fasudil on in vitro cultured cardiomyocytes (CMs) exposed to omethoate and its possible mechanism. METHODS: Cardiomyocytes were isolated from male SD rats and were then cultured in DMEM conventionally. The CMs were divided into different groups based on the doses of omethoate and fasudil in culture media. After 3, 6, 12, and 24 h of culture, the survival rate of CMs in each group was measured, the CMs in the medium-dose omethoate and medium-dose fasudil groups were subject to shortening amplitude measurement , and the content of lactate dehydrogenase (LDH) in culture media and expression of Bcl-2 and Bax in CMs were measured. RESULTS: Compared with the normal control group, each omethoate group showed significantly lower survival rate of CMs, which was negatively correlated with the dose of omethoate (P < 0.01). Compared with the normal control group, the medium-dose omethoate and medium-dose fasudil groups showed significantly decreased shortening amplitudes of CMs at all time points (P < 0.01), and the shortening amplitudes of CMs were significantly higher in the medium-dose fasudil group than in the medium-dose omethoate group after 12 h and 24 h of culture (P < 0.01). The LDH level was significantly higher in the medium-dose omethoate and medium-dose fasudil groups than in the normal control group, and the medium-dose fasudil group showed significantly lower LDH level than the medium-dose omethoate group (P < 0.01). Compared with those in the normal control group, the Bcl-2 expression in the medium-dose omethoate and medium-dose fasudil groups was decreased significantly, and the Bax expression in the medium-dose omethoate group was increased significantly (P < 0.01). Compared with the medium-dose omethoate group, the medium-dose fasudil group had significantly increased Bcl-2 expression and significantly decreased Bax expression (P < 0.01). CONCLUSION: Fasudil can inhibit the abnormal expression of apoptosis regulatory proteins (Bcl-2 and Bax) induced by omethoate, which might be one of the factors that reduce the toxic effect of omethoate on CMs.

High-risk behaviors related to AIDS/STDs infections among fishermen in Lv-si harbor, Jiangsu province / 中华流行病学杂志

Objective To investigate the high-risk behaviors related to acquared immune deficiency syndrome/sexually transmitted disease (AIDS/STDs) infection among fishermen in Lv-si harbor,Jiangsu province.Methods A cross-sectional study was designed to investigate the research participants' demographic characteristics,high-risk behaviors that related to AIDS/STDs.Logistic regression was performed to measure the associations between potential risk factors and reported potential high-risk sexual behavior.Results 817 fishermen participated in the study and casual or commercial sex activities appeared to be the main high-risk behavior for AIDS/STDs infection in the target population.The rates of casual and commercial sex reported were 18.1％ and 28.9％ among fishermen.Risk factors associated with AIDS/STDs related high-risk behaviors among fishermen were high mobility (OR=1.516,P=0.038),higher lifetime sex frequency (OR=1.422,P=0.002)and unmarried status ( OR =7.527,P=0.014).Protective factors against high-risk behaviors were low intake of alcohol (OR=0.803,P=0.053),negative STD history (OR=0.268,P=0.001 ),age of initial sexual intercourse at or older than 22 years (OR =0.440,P=0.000) of age,as well as negative attitude toward multiple sexual parmers (OR=0.662,P=0.023 ) and legitimation for commercial sex (OR=0.612,P=0.007).Conclusion There were risk behaviors of AIDS/STDs in those infected fishmen.Casual and commercial sex were common high-risk behaviors.