PHPB ameliorates memory deficits and reduces oxidative injury in Alzheimer's disease mouse model by activating Nrf2 signaling pathway.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

Crystal-Phase Engineering in Heterogeneous Catalysis.

The performance of a chemical reaction is critically dependent on the electronic and/or geometric structures of a material in heterogeneous catalysis. Over the past century, the Sabatier principle has already provided a conceptual framework for optimal catalyst design by adjusting the electronic structure of the catalytic material via a change in composition. Beyond composition, it is essential to recognize that the geometric atomic structures of a catalyst, encompassing terraces, edges, steps, kinks, and corners, have a substantial impact on the activity and selectivity of a chemical reaction. Crystal-phase engineering has the capacity to bring about substantial alterations in the electronic and geometric configurations of a catalyst, enabling control over coordination numbers, morphological features, and the arrangement of surface atoms. Modulating the crystallographic phase is therefore an important strategy for improving the stability, activity, and selectivity of catalytic materials. Nonetheless, a complete understanding of how the performance depends on the crystal phase of a catalyst remains elusive, primarily due to the absence of a molecular-level view of active sites across various crystal phases. In this review, we primarily focus on assessing the dependence of catalytic performance on crystal phases to elucidate the challenges and complexities inherent in heterogeneous catalysis, ultimately aiming for improved catalyst design.

[Influence of processing factors on honey-fried Codonopsis Radix].

The present study investigated the influence of heating and honey addition on the appearance, chemical component content, and pharmacological activity of Codonopsis Radix decoction pieces in the honey-frying process, and explored the processing mechanism of honey-fried Codonopsis Radix. The color, sweetness, and content of macromolecular components(e.g., oligosaccharides and polysaccharides) and small molecular components(e.g., lobetyolin and atractylenolide Ⅲ) of raw Codonopsis Radix, fried Codonopsis Radix, honey-mixed Codonopsis Radix, and honey-fried Codonopsis Radix were determined, and the antioxidant activities in vitro of their water extract, polysaccharide extract, and oligosaccharide extract were compared. The results showed that in terms of color and sweetness, compared with the raw Codonopsis Radix, the fried Codonopsis Radix slightly changed, the honey-mixed Codonopsis Radix changed significantly, and the honey-fried Codonopsis Radix changed with high significance. In terms of the content of lobetyolin, atractylenolide Ⅲ, and polysaccharides, the samples were ranked as raw Codonopsis Radix > fried Codonopsis Radix > honey-mixed Codonopsis Radix > honey-fried Codonopsis Radix, which indicated that heating and honey addition could reduce the content of these three components. In terms of the content of oligosaccharides, the samples were ranked as honey-fried Codonopsis Radix ≈ honey-mixed Codonopsis Radix > fried Codonopsis Radix ≈ raw Codonopsis Radix, indicating that honey addition could increase the content of oligosaccharides. In terms of antioxidant activity in vitro, ABTS radical scavenging ability of water extract, polysaccharides, and oligosaccharides of honey-fried Codonopsis Radix was most potent, while the change of antioxidant activity in vitro of each extract in the other three processed products was different. In short, both heating and honey addition can affect the appearance, chemical component content, and antioxidant activity in vitro of Codonopsis Radix decoction pieces, but the effect of the combination of the two factors is the best. The comprehensive analysis of the effects of heating and honey addition on Codonopsis Radix decoction pieces indicates that honey addition followed by heating at high temperature is the necessary condition for honey-fried Codonopsis Radix to enhance its activity.

Unstable plaques hide in heavily calcified coronary arteries.

Background: The napkin-ring sign (NRS) was accepted as unstable plaques at coronary computed tomography angiography (CCTA). However, the incidence is relatively low. We sought to assess whether the newly defined diamond-attenuation-sign [DAS, defined as a qualitative plaque feature in a mixed plaque (MP) on CCTA cross-section images by the presence of two features: a visual calcification (in the shape of a diamond) accompanied by an annular-shape lower attenuation plaque tissue surrounding the lumen like a ring], could be accurately identified as unstable atherosclerotic plaques. Methods: Eight heart transplant recipients (8 male; mean age, 48.5±11.6 years; range, 37-65 years) underwent CCTA exams prior to heart transplant surgery. Segment-based CCTA sections were independently evaluated for various plaque patterns including non-calcified plaque (NCP) with NRS (NCP-NRS), NCP without NRS (NCP-non-NRS), MP with DAS (MP-DAS), MP without DAS sign (MP-non-DAS), and calcified plaque (CP). Results: NCP-NRS plaques in 6.4% (23/358), NCP-non-NRS plaques in 24.0% (86/358), MP-DAS plaques in 18.2% (65/358), MP-non-DAS plaques in 20.1% (72/358), and calcified-plaques in 7.0% (25/358) of all cases. The specificity and positive predictive values of the MP-DAS and NCP-NRS signs to identify unstable plaque features were excellent (97.1% vs. 98.6%, 90.8% vs. 87.0%, respectively). DAS plaques were more frequently seen on CCTA exams than that of NRS (39.3% vs. 13.3%, respectively, P=0.001). The diagnostic performance of MP-DAS to identify unstable coronary lesions was superior compared to NCP-NRS [area under the receiver operating characteristic curve (ROC), 0.756; 95% CI: 0.717-0.791 vs. 0.558; 95% CI: 0.514-0.600, respectively, P<0.001]. Conclusions: Both the DAS and NRS had a high specificity and positive predictive value for the presence of unstable lesions. DAS was a better identification of unstable atherosclerotic plaques in the assessment of plaque-calcification-pattern (PCP).

Identification of pathology-confirmed vulnerable atherosclerotic lesions by coronary computed tomography angiography using radiomics analysis.

OBJECTIVES: To explore whether radiomics-based machine learning (ML) models could outperform conventional diagnostic methods at identifying vulnerable lesions on coronary computed tomographic angiography (CCTA). METHODS: In this retrospective study, 36 heart transplant recipients with coronary heart disease (CAD) and end-stage heart failure were included. Pathological cross-section samples of 350 plaques were collected and coregistered to patients' preoperative CCTA images. A total of 1184 radiomic features were extracted from CCTA images. Through feature selection and stratified fivefold cross-validation, we derived eight radiomics-based ML models for lesion vulnerability prediction. An independent set of 196 plaques from another 8 CAD patients who underwent heart transplants was collected to validate radiomics-based ML models' diagnostic accuracy against conventional CCTA feature-based diagnosis (presence of at least 2 high-risk plaque features). The performance of the prediction models was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI). RESULTS: The training group used to develop radiomics-based ML models contained 200/350 (57.1%) vulnerable plaques and the external validation group was composed of 67.3% (132/196) vulnerable plaques. The radiomics-based ML model based on eight radiomic features showed excellent cross-validation diagnostic accuracy (AUC: 0.900 ± 0.033). In the validation group, diagnosis based on conventional CCTA features demonstrated moderate performance (AUC: 0.656 [95% CI: 0.593 -0.718]), while the radiomics-based ML model showed higher diagnostic ability (0.782 [95% CI: 0.710 -0.846]). CONCLUSIONS: Radiomics-based ML models showed better diagnostic ability than the conventional CCTA features at assessing coronary plaque vulnerability. KEY POINTS: • CCTA has great potential in the diagnosis of vulnerable coronary artery lesions. • Radiomics model built through CCTA could discriminate coronary vulnerable lesions in good diagnostic ability. • Radiomics model could improve the ability of vulnerability diagnosis against traditional CCTA method, sensitivity especially.

Subendocardial Involvement as an Underrecognized Cardiac MRI Phenotype in Myocarditis.

Background Subendocardial late gadolinium enhancement (LGE) detected with cardiac MRI in myocarditis represents a diagnostic dilemma, since it may resemble myocardial ischemia. Purpose To explore and compare the histopathologic characteristics and clinical features and outcomes in patients with myocarditis with and without subendocardial involvement at cardiac MRI. Materials and Methods This retrospective study evaluated 39 patients with myocarditis pathologically proven by means of either endomyocardial biopsy or explant pathologic findings between 2015 and 2020. Patients were divided into two groups according to cardiac MRI phenotype: 18 with subendocardial involvement (mean age ± standard deviation, 40 years ± 17; 10 women) and 21 with no subendocardial involvement (mean age, 35 years ± 11; six women). The median follow-up period was 784 days (interquartile range [IQR], 90-1123 days). The Student t test, Mann-Whitney U test, and univariable Cox regression were used for statistical analyses. Results In the 18 patients with subendocardial involvement, 12 (67%) had lymphocytic myocarditis and six (33%) had giant cell myocarditis. Patients with subendocardial involvement compared with those without subendocardial involvement had lower left ventricular ejection fraction (mean ± standard deviation, 27% ± 11 vs 41% ± 19; P = .004), larger LGE extent (median, 13% [IQR, 10%-22%] vs 5% [IQR, 2%-17%]; P < .001), higher rates of cardiac death or transplant (eight of 18 patients [44%] vs one of 21 patients [4.8%]; P = .006), higher probability of giant cell myocarditis (six of 18 [33%] vs one of 21 [4.8%]; P = .02), and more major adverse cardiovascular events (MACE) (15 of 18 [83%] vs seven of 21 [33%]; P = .002). In a subgroup of patients with comparable LGE extent (median, 15% vs 16%; P = .40) and left ventricular ejection fraction (median, 27% vs 31%; P = .26), the prognostic difference in terms of MACE remained (15 of 17 patients [88%] vs five of 10 [50%]; P = .02). Conclusion Subendocardial involvement detected with cardiac MRI in myocarditis indicated more severe clinical features, including a higher frequency of severe lymphocytic myocarditis or giant cell myocarditis and worse prognosis. © RSNA, 2021 See also the editorial by de Roos in this issue.

Reversing pathology in a preclinical model of Alzheimer's disease by hacking cerebrovascular neoangiogenesis with advanced cancer therapeutics.

BACKGROUND: Cognitive decline leading to dementia, accompanied by the accumulation of amyloid-beta (Aß) in neuritic plaques together with the appearance of neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (tau), are previously noted hallmarks of Alzheimer's disease (AD). We previously discovered hypervascularity in brain specimens from AD patients and consistent with this observation, we demonstrated that overexpression of Aß drives cerebrovascular neoangiogenesis leading to hypervascularity and coincident tight-junction disruption and blood-brain barrier (BBB) leakiness in animal models of AD. We subsequently demonstrated that amyloid plaque burden and cerebrovascular pathogenesis subside when pro-angiogenic Aß levels are reduced. Based on these data, we propose a paradigm of AD etiology where, as a compensatory response to impaired cerebral blood flow (CBF), Aß triggers pathogenic cerebrovascular neoangiogenesis that underlies the conventional hallmarks of AD. Consequently, here we present evidence that repurposing anti-cancer drugs to modulate cerebrovascular neoangiogenesis, rather than directly targeting the amyloid cascade, may provide an effective treatment for AD and related vascular diseases of the brain. METHODS: We explored whether the anti-cancer drug, Axitinib, a small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR) can inhibit aberrant cerebrovascular neoangiogenic changes, reduce Aß deposits and reverse cognitive decline in an animal model of AD. One month post-treatment with Axitinib, we employed a battery of tests to assess cognition and memory in aged Tg2576 AD mice and used molecular analysis to demonstrate reduction of amyloid plaques, BBB leakage, hypervascularity and associated disease pathology. FINDINGS: Targeting the pro-angiogenic pathway in AD using the cancer drug, Axitinib, dramatically reduced cerebrovascular neoangiogenesis, restored BBB integrity, resolved tight-junction pathogenesis, diminishes Aß depositions in plaques and effectively restores memory and cognitive performance in a preclinical mouse model of AD. INTERPRETATION: Modulation of neoangiogenesis, in an analogous approach to those used to treat aberrant vascularization in cancer and also in the wet form of age-related macular degeneration (AMD), provides an alternative therapeutic strategy for intervention in AD that warrants clinical investigation. FUNDING: None.

Resection of Cardiac Pheochromocytoma With Cardiopulmonary Bypass.

We report a case of a 21-year-old man with a cardiac pheochromocytoma involving the right atrium and extending to the right ventricular inflow tract, which was diagnosed by somatostatin receptor scintigraphy. For the preoperative evaluation, we chose multiple methods of imaging to accurately describe the anatomic extent and location of the tumor and its surrounding tissues, which showed that no major coronary artery ran through the tumor. The tumor was resected with disease-free margins effectively and safely with the use of cardiopulmonary bypass and with cardiac arrest. The patient remained asymptomatic at the 3-month follow-up.

In Vivo Detection of Lipid-Core Plaques by Coronary CT Angiography: A Head-to-Head Comparison with Histologic Findings.

OBJECTIVE: We sought to distinguish lipid plaques using a CT quantitative pixel density histogram, based on the pathological diagnosis of lipid cores as the gold standard. MATERIALS AND METHODS: Eight patients awaiting heart transplantation due to end-stage coronary heart disease underwent coronary CT angiography (CCTA) spectroscopy prior to heart transplantation; coronary artery pathological analysis was performed for all patients. Lipid-core plaques were defined pathologically as manifesting a lipid core diameter > 200 µm, a circumference > 60 degrees, and a cap thickness < 450 µm. The percentage distributions of CT pixel attenuation ≤ 20, 30, 40, and 50 HU were calculated using quantitative histogram analysis. RESULTS: A total of 271 transverse sections were co-registered between CCTA and pathological analysis. Overall, 26 lipid cores and 16 fibrous plaques were identified by pathological analysis. There was no significant difference in median CT attenuation between the lipid and fibrous plaques (51 HU [interquartile range, 46-63] vs. 57 HU [interquartile range, 50-64], p = 0.659). The median percentage of CT pixel attenuation ≤ 30 HU accounted for 11% (5-17) of lipid-core plaques and 0% (0-2) of fibrous plaques (p < 0.001). The sensitivity and specificity of the method for diagnosing lipid plaques by the average CT pixel attenuation ≤ 30 HU were 80.8% and 87.5%, respectively. The area under the receiver operator characteristics curve was 0.898 (95% confidence interval: 0.765-0.970; 3.0% was the best cut-off value). The diagnostic performance was significantly higher than those of the average pixel CT attenuation percentages ≤ 20, 40, and 50 HU and the mean CT attenuation (p < 0.05). CONCLUSION: In in vivo conditions, with the pathological lipid core as the gold standard, quantification of the percentage of average CT pixel attenuation ≤ 30 HU in the histogram can be useful for accurate identification of lipid plaques.

Safety and efficacy of superior vena cava isolation using the second-generation cryoballoon ablation in a canine model.

BACKGROUND: The safety and efficacy of superior vena cava (SVC) isolation (SVCI) using second-generation cryoballoon (CB) ablation remains unknown. METHODS: Electrical isolation of SVC was attempted using the second-generation CB ablation catheter in 14 canines. Ablation duration was randomized to either 90 s (7 canines) or 120 s (7 canines). SVC venography was performed to identify the SVC-right atrium (RA) junction. The 28-mm CB was positioned above SVC-RA junction. Repeat electrophysiological assessment in the live animals was conducted 40-60 days post-ablation, after which animals were euthanized for histological examination. RESULTS: Acute SVCI was successfully performed in all canines. No significant differences in numbers of freezes (1.7 ±â€¯0.8 vs. 1.5 ±â€¯0.5, p = 0.658), time to isolation (TTI) (24.3 ±â€¯8.1s vs. 22.7 ±â€¯9.0s, p = 0.297), temperature at isolation (-23.4 ±â€¯12.5 °C vs. -21.5 ±â€¯11.1 °C, p = 0.370), and nadir temperature (-51.2 ±â€¯6.2 °C vs. -53.3 ±â€¯7.0 °C, p = 0.195) were observed between the 90-s and 120-s groups. There were no procedural complications except one transient sinus bradycardia in the 120-s group. After ablation, animals survived for 51 ±â€¯5 days. Chronic SVCI was achieved in 6 of 7 (85.7%) SVCs in the 90-s group and 7 of 7 SVCs (100%) in the 120-s group (p = 0.299). Histological analysis revealed that a circumferential transmural lesion was achieved in all isolated SVCs. No sinus node (SN) and phrenic nerve injuries were observed. The minimum distance between ablation lesion and SN was 5.1 ±â€¯3.0 mm. CONCLUSIONS: The second-generation CB ablation catheter is both safe and effective in achieving SVC isolation in a canine model. Effective SVCI was found in the 90-s dosing strategy.

Met-Hemoglobin Is a Biomarker for Poor Oxygen Delivery in Infants Following Surgical Palliation.

BACKGROUND: Infants with cyanotic congenital heart disease demonstrate wide fluctuations in hemoglobin (Hb), oxygen saturation, and cardiac output following palliation. Methemoglobin (Met-Hb), the product of Hb oxidation, may represent a compensatory mechanism during hypoxia and may be utilized as a biomarker. METHODS: Arterial and venous Met-Hb levels were obtained from infants requiring palliation. The primary outcome was to describe the relationship between Met-Hb and other indices of tissue oxygenation (venous saturation, estimated arteriovenous oxygen difference [Est AV-Diff], and lactate). Secondary outcomes were to determine the impact of elevated Met-Hb levels ≥1.0% and the effect of red blood cell (RBC) transfusion on Met-Hb levels. RESULTS: Fifty infants and 465 Met-Hb values were studied. Venous Met-Hb levels were significantly higher than arterial levels (venous: 0.84% ± 0.36% vs arterial: 0.45% ± 0.18%; P < .001). Venous Met-Hb demonstrated a significant inverse relationship with venous oxygen saturation (R = -0.6; P < .001) and Hb (R = -0.3, P < .001) and a direct relationship with the Est AV-Diff (R = 0.3, P < .001). A total of 129 (29.6%) venous Met-Hb values were elevated (≥1.0%) and were associated with significantly lower Hb and venous saturation levels and higher Est AV-Diff and lactate levels. Methemoglobin levels decreased significantly following 65 RBC transfusions (0.94 ± 0.40 vs 0.77 ± 0.34; P < .001). Linear mixed models demonstrated that higher venous Met-Hb levels were associated with lower measures of tissue oxygenation and not related to any preoperative clinical differences. CONCLUSION: Methemoglobin may be a clinically useful marker of tissue oxygenation in infants following surgical palliation.

Hepatocyte growth factor inhibits tubular epithelial­myofibroblast transdifferentiation by suppression of angiotensin II via the JAK2/STAT3 signaling pathway.

Tubular epithelial­myofibroblast transdifferentiation (TEMT) is important in the development of chronic renal failure. The present study investigated whether hepatocyte growth factor (HGF) inhibits TEMT, and whether this function may be associated with the inhibition of angiotensin II (AngII) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Human HK­2 kidney proximal tubular cells were divided into 4 groups and treated with AngII (1x10­6 M), HGF (8x10­3 M), AngII plus HGF or control conditions, followed by an assessment of apoptosis induction and the expression levels of α­smooth muscle actin (α­SMA), which is a marker of TEMT. as well as the activation level of JAK2, phosphorylated (p)­JAK2, STAT3 and p­STAT3 signaling pathways. In HK­2 cells, α­SMA mRNA and protein expression levels increased following treatment with AngII, however, decreased expression was observed following exposure to HGF. HGF counteracted the AngII­induced increase in the expression of α­SMA in HK­2 cells. Similar expression profiles were observed for the phosphorylated forms of JAK2 and STAT3, indicating the possible involvement of this signaling pathway. The results demonstrated that treatment of cells with AngII was associated with the induction of apoptosis when compared with the control. By contrast, treatment with HGF attenuated AngII­induced apoptosis. The results suggested that HGF may inhibit TEMT by inhibiting AngII through the JAK2/STAT3 signaling pathway in HK­2 cells and HGF may prevent apoptosis induced by AngII. The present study provides a basis for understanding the mechanisms involved in the inhibition of TEMT by HGF, which requires further investigation.

Protective effect of olmesartan against cardiac ischemia/reperfusion injury in spontaneously hypertensive rats.

Olmesartan, as a new angiotensin II receptor blocker, has shown beneficial effects on cardiovascular diseases. Nevertheless, the effect of olmesartan on ischemia/reperfusion (I/R) injury in the hypertensive heart has not been investigated. Therefore, the present study aimed to investigate the effect of olmesartan on I/R injury in spontaneously hypertensive rats (SHRs). Experimental groups were designed with a 2×2 factorial design for olmesartan and I/R effects. In the I/R group, the left anterior descending coronary artery (LAD) was ligated for 40 min followed by a 180-min reperfusion. In the sham group, SHRs underwent the same surgical procedure as the I/R group, with the exception that the suture passed under the LAD without being tightened. In the Olm-I/R group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the I/R group. In the Olm-sham group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the sham group. Infarct size was measured for the I/R and Olm-I/R groups. Blood pressure (BP), serum creatine kinase (CK), left ventricular mass index (LVMI), high mobility group box 1 (HMGB1) protein expression levels and hypoxia-inducible factor-1α (HIF-1α) mRNA expression levels were measured for all four groups. Olmesartan significantly reduced BP and LVMI in the olmesartan-treated SHRs compared with those in the SHRs that were not treated with olmesartan. HMGB1 and HIF-1α expression levels were significantly decreased in the Olm-sham and Olm-I/R groups compared with those in the sham and I/R groups, respectively. The proportional increase in HIF-1α expression due to I/R was greater in the olmesartan-treated rats than in the untreated rats. Serum CK levels were significantly reduced in the Olm-I/R group compared with those in the I/R group. In conclusion, olmesartan ameliorates left ventricular hypotrophy and protects the heart against I/R injury in addition to lowing BP in SHRs. The protective effect of olmesartan may be partly due to its antioxidative and anti-inflammatory properties.

Clinical characteristics and prognosis of 60 patients with midventricular obstructive hypertrophic cardiomyopathy.

BACKGROUND: Midventricular obstructive hypertrophic cardiomyopathy (MVOHCM) is a rare form of hypertrophic cardiomyopathy. Knowledge regarding the diagnosis, morbidity and cardiovascular mortality is limited. In this study, we aimed to describe the long-term outcomes of patients with MVOHCM followed in a tertiary referral centre.Methods A retrospective study of 60 patients with MVOHCM diagnosed at FuWai Hospital was performed. Clinical features, mortality and cardiovascular morbidity were analysed. RESULTS: The 60 patients with MVOHCM represented 2.9% of all the hypertrophic cardiomyopathy cases (n = 2068). At diagnosis, the mean age was 40.2 ±â€Š15.0 years. During 7.1 ±â€Š6.3 years of follow-up after diagnosis, the cardiovascular mortality was 15.0%. The probability of survival at 10 years was 77.0 ±â€Š8.0%. The following two predictors of cardiovascular mortality were identified: severe ventricular septal hypertrophy at least 30  mm (hazard ratio, 3.19; P = 0.031) and unexplained syncope (hazard ratio, 4.59; P = 0.002) at baseline. Thirty patients (50.0%) had one or more morbid events, and the most frequent was nonsustained ventricular tachycardia. Apical aneurysm formation was identified in 20% of patients, and the patients with apical aneurysms were more inclined to experience nonsustained ventricular tachycardia than patients without apical aneurysm (58.3 vs. 16.7%; P = 0.003). Peak pressure gradient at least 70  mm Hg (hazard ratio, 3.00; P = 0.01) at baseline was identified as the only predictor of apical aneurysm. CONCLUSION: In Chinese patients, MVOHCM is associated with an unfavourable prognosis of cardiovascular mortality. One-half of these patients experience major cardiovascular events, and 20% develop an apical aneurysm, which significantly increases arrhythmia events. These data warrant measures to ensure the early recognition of MVOHCM followed by appropriate therapeutic interventions.

Management of focal atrial tachycardias originating from the atrial appendage with the combination of radiofrequency catheter ablation and minimally invasive atrial appendectomy.

BACKGROUND: Focal atrial tachycardias (ATs) originating from the left and the right atrial appendage (AA) were the most difficult to eliminate. OBJECTIVE: To evaluate the safety and long-term efficacy of minimally invasive surgical atrial appendectomy in combination with radiofrequency catheter ablation (RFCA) in the management of focal atrial appendage tachycardias (AATs). METHODS: We included 42 consecutive patients with 42 AATs confirmed by activation mapping and contrast venography. Thirty of them were successfully managed with RFCA (RFCA-successful group), while the remaining 12 (28.6%) finally resorted to video-assisted thoracoscopic atrial appendectomy owing to RFCA failure (resort-to-surgery group). We searched for predictors of RFCA failure, and the need for surgery by using a binomial logistic regression model. RESULTS: In the RFCA-successful group, 6 (20.0%) patients experienced recurrence and re-do ablation and 11 (36.7%) AATs originated from distal AAs. In the resort-to-surgery group, the tachycardias involved exclusively distal AAs and required more RFCA attempts compared with those of the RFCA-successful group (1.58 ± 0.51 vs 1.20 ± 0.41; P = .0165). During atrial appendectomy, incessant ATs were terminated immediately after resection of the AA at the base. Long-term success was achieved in all 42 patients with a follow-up of 29.1 ± 17.5 months. No complications occurred. Fourteen patients with tachycardia-induced cardiomyopathy recovered fully. We identified origin at distal AATs and longer time to tachycardia termination by ablation as predictors of RFCA failure and the need for surgical intervention. CONCLUSION: ATs originating from the distal portion of AA were more refractory to RFCA. The combination of catheter ablation and video-assisted thoracoscopic atrial appendectomy was an effective strategy to manage AATs.

Pathological changes, TGF-ß1 expression, and the effects of hepatocyte growth factor in 5/6 nephrectomized rats.

Several studies have shown that hepatocyte growth factor (HGF) ameliorates chronic renal failure, but its mechanism of action is unclear. This study was designed to test the delivery of HGF in the PCI-neo vector, using the 5/6 nephrectomized rat as a model for chronic renal failure, and to confirm that this protective function is associated with decreased protein expression of transforming growth factor-beta1 (TGF-ß1). Rats were randomly divided into the following groups: Control (untreated), PCI-neo (vector control), 5/6 nephrectomy, and PCI-neo-HGF. Rats were sacrificed at both the fifth and ninth week after 5/6 nephrectomy. Kidney specimens were used for pathological examination (hematoxylin-eosin staining), and detection of TGF-ß1 protein (Western blot and immunohistochemistry) expression. Blood urea nitrogen, serum creatinine, and 24-h urinary protein excretion (UPE) were increased, renal interstitium was seriously injured, and TGF-ß1 protein expression was elevated in 5/6 nephrectomized rats compared to control rats at either time point. Red blood cell and hemoglobin levels decreased in the ninth week after 5/6 nephrectomy. PCI-neo-HGF expression ameliorated the aforementioned changes and decreased TGF-ß1 expression, not only in the fifth week, but also in the ninth week after surgery. The process of renal injury in the 5/6 nephrectomized rat was consistent with that of chronic renal failure. The increase in TGF-ß1 expression was maintained after 5/6 nephrectomy. HGF relieved chronic renal failure, this protection was associated with down-regulation of TGF-ß1 protein expression, and the protective effects were long-term and stable after 5/6 nephrectomy.

Hepatocyte growth factor-induced amelioration in chronic renal failure is associated with reduced expression of α-smooth muscle actin.

This study aimed to examine whether hepatocyte growth factor (HGF) can improve renal function in 5/6 nephrectomized rats and investigate whether this function is associated with a decrease in α-smooth muscle actin (α-SMA) expression in rat glomerulus mesangial cells and renal interstitium. Rats were randomly divided into the following groups: control, PCI-neo, sham-operation, 5/6 nephrectomy, and low-dose and high-dose PCI-neo-HGF. Rats were killed in the ninth week after 5/6 nephrectomy, and the kidney specimens were subjected to pathological examination by Hematoxylin-Eosin staining and detection of α-SMA expression by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. The results showed that blood urea nitrogen and serum creatinine levels were increased, renal interstitium was injured, and α-SMA expression was elevated in 5/6 nephrectomized rats compared with that in control. The above changes were ameliorated in the rats injected with PCI-neo-HGF vector. At the molecular level we found that PCI-neo-HGF repressed α-SMA expression in mesangial cells stimulated by lipopolysaccharide. In conclusion, our data suggest that HGF can relieve chronic renal failure, and this protection is associated with the down-regulation of α-SMA expression in mesangial cells and renal interstitium.