Ex vivo liver resection and autotransplantation as alternative to allotransplantation for end-stage hepatic alveolar echinococcosis.

BACKGROUND & AIMS: Radical resection is the best treatment for patients with advanced hepatic alveolar echinococcosis (AE). Liver transplantation is considered for selected advanced cases; however, a shortage of organ donors and the risk of postoperative recurrence are major challenges. The aim of this study was to assess the clinical outcomes of ex vivo liver resection and autotransplantation for end-stage AE. METHODS: In this prospective study, 69 consecutive patients with end-stage hepatic AE were treated with ex vivo resection and liver autotransplantation between January 2010 and February 2017. The feasibility, safety and long-term clinical outcome of this technique were assessed. RESULTS: Ex vivo extended hepatectomy with autotransplantation was successful in all patients without intraoperative mortality. The median weight of the graft and AE lesion were 850 (370-1,600) g and 1,650 (375-5,000) g, respectively. The median duration of the operation and anhepatic phase were 15.9 (8-24) h and 360 (104-879) min, respectively. Six patients did not need any blood transfusion. Complications higher than IIIa according to Clavien classification were observed in 10 patients. The 30-day-mortality and overall mortality (>90 days) were 7.24% (5/69) and 11.5% (8/69), respectively. The mean hospital stay was 34.5 (12-128) days. Patients were followed-up systematically for a median of 22.5 months (14-89) without recurrence. CONCLUSION: This is the largest series assessing ex vivo liver resection and autotransplantation in end-stage hepatic AE. This technique could be an effective alternative to liver transplantation in patients with end-stage hepatic AE, with the advantage that it does not require an organ nor immunosuppressive agents. LAY SUMMARY: Ex vivo liver resection and autotransplantation were performed in a large series of patients with end-stage hepatic alveolar echinococcosis. The results showed that this surgical option was feasible, with acceptable postoperative mortality, but 100% disease-free survival in survivors. Careful patient selection, as well as precise assessment for size and quality of the remnant liver are key to successful surgery.

VEGF-C-mediated cardiac lymphangiogenesis in high salt intake accelerated progression of left ventricular remodeling in spontaneously hypertensive rats.

High salt (HS) diet can accelerate the progress of hypertensive left ventricular (LV) remodeling. But the detailed mechanism remains poorly understood. We hypothesized HS intake could impact cardiac lymphangiogenesis through tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway which might play an important role in HS intake accelerated LV remodeling. Eight-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were randomized to 0.5% NaCl (Low salt, LS) and 8% NaCl (high salt, HS) diets for 12 weeks. LV remodeling was determined by echocardiography. LV invasive hemodynamic analysis and morphologic staining (cardiomyocyte hypertrophy, collagen deposition, TonEBP expression, macrophage infiltration and lymphatic density) were performed at the time of sacrifice. The blood pressure of SHR-HS group was significantly increased compared to SHR-LS and WKY groups. Meanwhile, The LV chamber size was markedly enlargement, LV function apparently compromised accompanied with a severe macrophage infiltration, and fibrosis in the perivascular and interstitium of LV compared with SHR-LS group. Furthermore, the expression levels of VEGF-C, TonEBP, and lymphatic markers in SHR-HS group were significantly increased parallel with apparent lymphangiogenesis compared with SHR-LS group. Our work indicates that TonEBP/VEGF-C signaling pathway was up-regulated in HS intake accelerated hypertensive LV remodeling process that may be valuable for further investigation.

Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice.

CONTEXT: Astragaloside IV (ASI) is a major and active saponin derivative of Astragalus membranaceus (Fisch) Bge. The anti-inflammatory properties of ASI are important for its cardioprotective effects. However, the molecular mechanisms of the protective effect of ASI on lipopolysaccharide (LPS)-induced cardiac dysfunction is yet to be elucidated. OBJECTIVE: This study was designed to investigate the therapeutic effects and possible mechanisms of ASI against LPS-induced septic cardiac dysfunction and inflammation in mice. MATERIALS AND METHODS: Mice were intraperitoneally injected with ASI (20 mg/kg) for 1 week before LPS challenge (10 mg/kg, i.p.). Left ventricular performance and morphology were analyzed using echocardiography 6 h after LPS induction. Activities of lactate dehydrogenase (LDH) in serum were measured and serum levels of cardiac troponin I (cTnI) were quantified by ELISA. Serum levels of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-1ß were also quantified by ELISA. The protein expressions of NF-кB p65 and p-AKT in heart tissues were detected using Western blot analysis. RESULTS: LPS administration deteriorated cardiac function and was attenuated by ASI pretreatment. ASI attenuated LPS-induced the increase of LDH and cTnI activities in mice. ASI also prevented NF-кB activation and subsequent myocardial inflammatory responses in endotoxemic mice. The effects of ASI were closely associated with the phosphatidylinositol-3-kinase (PI3K/AKT) signaling pathway, as characterized by ASI-induced activation in phospho-Akt. ASI also extended the lifespan of toxemic mice. CONCLUSION: ASI significantly attenuated LPS-induced cardiac dysfunction and inflammatory mediator production by inhibiting NF-кB and activating PI3K/AKT signaling pathway.

Overexpression of VEGF-C attenuates chronic high salt intake-induced left ventricular maladaptive remodeling in spontaneously hypertensive rats.

Recent studies have shown that the tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway-induced lymphangiogenesis provides a buffering mechanism for high salt (HS) intake-induced elevation of blood pressure (BP). Moreover, blocking of TonEBP/VEGF-C signaling by mononuclear phagocyte depletion can induce salt-sensitive hypertension in rats. We hypothesized that HS intake could have an impact on cardiac lymphangiogenesis, and regulation of VEGF-C bioactivity, which is largely through the main receptor for VEGFR-3, may modulate HS intake-induced left ventricular remodeling. We demonstrated upregulation of TonEBP, increased macrophage infiltration, and enhanced lymphangiogenesis in the left ventricles of spontaneously hypertensive rats (SHR) that were fed a HS diet (8.0% NaCl). Then, retrovirus vectors capable of overexpression (ΔNΔC/VEGF-C/Cys152Ser, used for overexpressing VEGF-C) and blocking (VEGFR-3-Rg, used for trapping of bioactive VEGF-C) of VEGF-C and control vector (pLPCX) were intravenously administered to SHR from week 9 of a 12-wk HS loading period. At the end of the HS challenge, overexpression of VEGF-C led to enhanced cardiac lymphangiogenesis, decreased myocardial fibrosis, and macrophage infiltration, preserved left ventricular functions, as well as decreased blood pressure level compared with the HS group and the control vector-treated HS group. In contrast, systemic blocking of VEGF-C was associated with elevation of blood pressure level and an exacerbation of hypertensive left ventricular remodeling, as indicated by increased fibrosis and macrophage infiltration, and diminished lymphangiogenesis. Hence, our findings highlight that VEGF-C/VEGFR-3 is a promising therapeutic target to attenuate hypertensive left ventricular remodeling induced by HS intake, presumably via blood pressure-dependent and -independent mechanisms.

Decreased circulating microRNA-223 level predicts high on-treatment platelet reactivity in patients with troponin-negative non-ST elevation acute coronary syndrome.

To investigate the relationship between circulating microRNA 223 (miR-223) levels and clopidogrel responsiveness in patients with coronary heart disease. A total of 62 consecutive patients with troponin-negative non-ST elevation acute coronary syndrome (NSTE-ACS) scheduled for elective percutaneous coronary intervention were enrolled. The plasma circulating miR-223 levels were quantified by real-time PCR, and platelet reactivity was determined by platelet reactivity index (PRI), measured by vasodilator-stimulated phosphoprotein (VASP) phosphorylation flow cytometry after 300 mg (for at least 24 h) or 75 mg clopidogel (for at least 5 days) plus aspirin treatment. All subjects were dichotomized according to PRI median (normal-responders: PRI ≤ 56.3%, n = 31 and low-responders: PRI > 56.3%, n = 31). Compared with normal-responders, circulating miR-223 level was significantly decreased in low-responders (P = 0.007). In addition, miR-223 level was statistically correlated with PRI (Spearman r = -0.379, P = 0.002). Stepwise binary logistic regression analysis revealed that among factors that potentially influence platelet reactivity (CYP2C19*2/*3 loss-of-function genotypes, use of calcium channel blockers/proton-pump inhibitors, age, diabetes and smoking), decreased circulating miR-223 level was the only independent predictor for the presence of PRI-determined lower responders (OR 0.111, 95% CI 0.018-0.692, P = 0.019). Our data suggest that circulating miR-223 may serve as a novel biomarker for assessment of clopidogrel responsiveness in troponin-negative NSTE-ACS patients.

Monocyte subsets and monocyte-platelet aggregates in patients with unstable angina.

Monocyte subsets and monocyte-platelet aggregates (MPAs) play important role in atherosclerosis and thrombosis. We aimed to determine their changes in patients with unstable angina (UA). In this cross-sectional case-control study, Global Registry of Acute Coronary Events (GRACE) score was determined in 95 UA patients without elevated troponin level. Thirty age-and-sex matched stable coronary heart disease (CHD) subjects served as control group. The classical (CD14++CD16-, Mon1), the intermediate (CD14++CD16+, Mon2) and the non-classical (CD14+CD16++, Mon3) monocytes, as well as subset-specific MPAs, were measured by flow cytometry. Compared with stable CHD patients, UA patients had increased Mon2 and Mon3 counts (all P < 0.001). For UA subjects, compared with GRACE score-determined low risk patients (GRACE score ≤108, n = 70), intermediate-to-high risk patients (GRACE score >108, n = 25) had higher counts of Mon2 and total MPAs, as well as Mon1- and Mon2-associated MPAs (all P < 0.001). Adjusted binary logistic regression analysis revealed that increased counts of Mon2 subset (for per 5 cells/µL increase, OR 1.186, 95% CI 1.044-1.347, P = 0.009), Mon2 MPAs (for per 5 cells/µL increase, OR 1.228, 95% CI 1.062-1.421, P = 0.006) and total MPAs (for per 5 cells/µL increase, OR 1.072, 95 % CI 1.010-1.137, P = 0.022) independently associated with GRACE score-determined intermediate-to-high risk UA patients. In UA patients with intermediate-to-high risk (determined by GRACE score), counts of Mon2 subset, Mon2-associated MPAs and total MPAs are increased, which are independent of traditional risk factors.

Fifty-five cases of hepatic alveolar echinococcosis combined with lymph node metastasis: A retrospective study.

BACKGROUND: Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis (AE). Currently, there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial. Radical hepatectomy combined with regional lymph node dissection is a better treatment. AIM: To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy. METHODS: A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed. Fifty-five patients with combined lymph node metastasis were analysed for their clinical data, diagnosis and treatment methods, follow-up efficacy, and characteristics of lymph node metastasis. Finally, we comparatively analysed the lymph node metastasis rates at different sites. Categorical variables are expressed as frequencies and percentages, and the analysis of difference was performed using the χ 2 test. The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables. RESULTS: A lymph node metastasis rate of 8.8% (55/623) was reported in patients with hepatic AE, with a female predilection (69.1%) and a statistically significant sex difference (χ 2 = 8.018, P = 0.005). Of the 55 patients with lymph node metastasis, 72.7% had a parasite lesion, neighbouring organ invasion, and metastasis stage of P3N1M0 and above, of which 67.3%, 78.2%, and 34.5% of hepatic AE lesions invaded the bile ducts, blood vessels, and distant metastases, respectively. Detection rates of lymph node metastasis of 16.4%, 21.7%, and 34.2% were reported for a preoperative abdominal ultrasound, magnetic resonance imaging, and computed tomography examinations. All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection. After surgery, a routine pathological examination was conducted on the resected lymph nodes. A total of 106 positive lymph nodes were detected in six groups at various sites, including 51 single-group metastasis cases and four multi-group metastasis cases. When the metastasis rates at different sites were statistically analysed, we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites (χ 2 = 128.089, P = 0.000 < 0.05). No statistical difference was observed in the metastasis rate between the five other groups. Clavien-Dindo grade IIIa complication occurred in 14 cases, which improved after administering symptomatic treatment. Additionally, lymph node dissection-related complications were not observed. Recurrence after 2 years was observed in one patient. CONCLUSION: Lymph node metastasis is a rare form of metastasis in hepatic AE, which is more frequent in women. Para-hepatoduodenal ligament lymph nodes are commonly observed. Radical hepatectomy combined with regional lymph node dissection is a safe, effective, and feasible treatment for liver AE combined with lymph node metastasis.

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

Complex inferior vena cava reconstruction during ex vivo liver resection and autotransplantation: A case report.

BACKGROUND: Ex vivo liver resection and autotransplantation (ELRA) is an essential approach for treating patients with end-stage hepatic alveolar echinococcosis (AE), and its surgical indications involve severe invasion of important hepatic vessels, which makes in vivo resection impossible. Revascularization is a major step in the process of ELRA, which is extremely challenging when the invaded vessels have huge defects. CASE SUMMARY: Herein, we have reported the case of a 26-year-old patient with hepatic AE in an autologous liver graft who underwent complex inferior vena cava (IVC) reconstruction using disease-free IVC, autologous portal vein fragments, and umbilical vein within the ligamentum teres hepatis. The patient showed good surgical recovery without vascular-related complications during the long-term follow-up. CONCLUSION: We reviewed three studies that have reported complex revascularization of the IVC. This case report and systematic review showed that the use of autologous perihepatic vessels prevents donor-area trauma, immune rejection, and other adverse reactions. When the blood vessel is severely invaded and a single vascular material cannot repair and reconstruct the defect, ELRA may provide a safe and feasible surgical approach, which has good prospects for clinical application.

An ultrasensitive bacterial imprinted electrochemical sensor for the determination of Lactobacillus rhamnosus GG.

An ultrasensitive label-free electrochemical sensor based on a homemade imprinted polypyrrole (PPy) polymer film was prepared to achieve quantitative determination of Lactobacillus rhamnosus GG (LGG). The LGG-imprinted polymer (LIP) film was deposited on a portable screen-printed electrode (SPE) via electropolymerization, which constituted an independent integrated system. The main preparation parameters of the LIP sensor were investigated to obtain optimal performance. Under optimized conditions, the peak current response of the LIP sensor showed a linear relationship with the logarithmic value of LGG concentration in the range from 101 to 109 CFU mL-1 and a detection limit of 5 CFU mL-1. The proposed LIP sensor has achieved efficient, ultrasensitive, highly selective, and cost-effective detection of LGG and can be further developed for practical applications in the quality inspection and development of probiotic products.

Potassium cobalt hexacyanoferrate as a peroxidase mimic for electrochemical immunosensing of Lactobacillus rhamnosus GG.

In this paper, the potassium cobalt hexacyanoferrate (II), K2CoFe(CN)6, with peroxidase-like activity was used for the fabrication of a novel label-free Lactobacillus rhamnosus GG (LGG) electrochemical immunosensor. The K2CoFe(CN)6 nanocubes were made by a simple hydrothermal method and followed by low-temperature calcination. In addition to structural characterization, the peroxidase-mimicking catalytic property of the material was confirmed by a chromogenic reaction. It is known that H2O2 can oxidize electroactive thionine molecules under the catalysis of horseradish peroxidase (HRP). In this nanozyme-based electrochemical immunoassay, due to the steric hindrance, the formation of immune-complex of LGG and LGG antibody on the modified GCE inhibits the catalytic activity of the peroxidase mimics of K2CoFe(CN)6 and thus reduced the current signal. Therefore, the developed electrochemical immunosensor achieved quantitative detection of LGG. Under optimal conditions, the linear range of the sensor was obtained from 101 to 106 CFU mL-1 with a minimum detection limit (LOD) of 12 CFU mL-1. Furthermore, the immunosensor was successfully applied in the quantitative detection of LGG in dairy product samples with recoveries ranging from 93.2% to 106.8%. This protocol presents a novel immunoassay method, which provides an alternative implementation pathway for the quantitative detection of microorganisms.

A Novel Hepatectomy Model in Mice Using a Gutta Cutter Tool: A Feasibility Study and Preliminary Results.

BACKGROUND: A simple and reproducible model of hepatectomy provides an essential basis for the study of liver regeneration. However, current rodent models of hepatectomy involve lobectomy, which cannot simulate clinical liver resection with surgical margins. The main purpose of this study was to evaluate a novel murine modeling technique for hepatectomy using a gutta cutter. METHODS: Seventy-five C57BL/6 mice were randomly divided into 3 groups (n = 25 mice per group). Group 1 (control) underwent single ligature of the left lobe. Group 2 underwent left lobe local (5-mm diameter) hepatectomy by gutta cutter. Group 3 underwent partial left lobe resection (1.5 cm) by gutta cutter. Postoperative complications were analyzed. Serum aspartate transaminase, alanine aminotransferase, alkaline phosphatase, urea nitrogen, interleukin 6, and tumor necrosis factor-α were detected using an automatic biochemical analyzer. Hematoxylin-eosin and immunohistochemical staining was used to examine pathology, proliferating cell nuclear antigen, caspase-3, CD34, signal transducer and activator of transcription 3 (STAT-3), and phosphorylated STAT-3 (p-STAT-3). RESULTS: Major postoperative complications, hepatic enzymes, kidney function, interleukin 6, and tumor necrosis factor-α were similar among the groups (all P > .05). Histology showed little necrosis and a clear surgical boundary in groups 2 and 3. Groups 1 and 3 had higher positive cell levels (proliferating cell nuclear antigen, CD34, p-STAT-3) than group 2 (P < .05). There were no significant differences in caspase-3 and STAT-3 positive cells. CONCLUSIONS: Hepatectomy in mice using a gutta cutter to better mimic human liver resection shows potential as an alternative and safe animal model. This model may be useful in investigating methods of promoting liver regeneration.

Approaches to reconstruction of inferior vena cava by ex vivo liver resection and autotransplantation in 114 patients with hepatic alveolar echinococcosis.

BACKGROUND: Hepatic alveolar echinococcosis (AE) is most commonly found in retrohepatic inferior vena cava (RHIVC). Ex vivo liver resection and autotransplantation (ELRA) can better realize the radical resection of end-stage hepatic AE with severely compromised hepatocaval confluences, and reconstruction of the affected vessels. Currently, there is a scarcity of information regarding RHIVC reconstruction in ELRA. AIM: To propose reasonable RHICV reconstruction strategies for ex vivo liver resection and autotransplantation. METHODS: We retrospectively summarized the clinical data of 114 patients diagnosed with hepatic AE who treated by ELRA in our department. A total of 114 patients were divided into three groups according to the different reconstruction methods of RHIVC: Group A with original RHIVC being repaired and reconstructed (n = 64), group B with RHIVC being replaced (n = 43), and group C with RHIVC being resected without reconstruction (n = 7). The clinical data of patients, including the operation time, anhepatic phase, intraoperative blood loss, complications and postoperative hospital stay, were analyzed and the patients were routinely followed up. The normally distributed continuous variables were expressed as means ± SD, whereas the abnormally distributed ones were expressed as median and analyzed by analysis of variance. Survival curve was plotted by the Kaplan-Meier method. RESULTS: All patients were routinely followed up for a median duration of 52 (range, 12-125) mo. The 30 d mortality rate was 7.0% (8/114) and 7 patients died within 90 d. Among all subjects, the inferior vena cava (IVC)-related complication rates were 17.5% (11/63) in group A and 16.3% (7/43) in group B. IVC stenosis was found in 12 patients (10.5%), whereas thrombus was formed in 6 patients (5.3%). Twenty-two patients had grade III or higher complications, with the complication rates being 17.2%, 16.3%, and 57.1% in the three groups. The average postoperative hospital stay in the three groups was 32.3 ± 19.8, 26.7 ± 18.2, and 51.3 ± 29.4 d (P = 0.03), respectively. CONCLUSION: ELRA can be considered a safe and feasible option for end-stage hepatic AE patients with RHIVC infiltration. The RHIVC reconstruction methods should be selected appropriately depending on the defect degree of AE lesions in IVC lumen. The RHIVC resection without any reconstruction method should be considered with caution.

Changes in the intestinal microbiota of healthy adults induced by brown yogurt and relationships of bacterial taxa with specific components.

Yogurt consumption shows a wide range of effects on the gut microbial composition, and correlation of components in yogurt with the changes of gut microbia remains largely uncharacterized. We aimed to determine the effect of brown yogurt (SSN) on the composition of the gut microbiota and to explore the effects of the major components. We performed a randomized study of 70 healthy adults to compare the effects of SSN and standard probiotic-containing yogurt (YJD) during a 28-day intervention and a 10-day follow-up period. The results showed that the SSN group showed significant increases in the butyrate-producer Akkermansia muciniphila, Ruminococcus, and Veillonella (p < 0.05), whereas the YJD group showed increases in the butyrate-producer Megasphaera, Anaerostipes, and Eubacterium. There were reductions in the potential pathogens Haemophilus parainfluenzae and Gemmiger formicilis in both groups (p < 0.05). The SSN group had more Faecalibacterium prausnitzii, Prevotella copri, Bifidobacterium and B. longum than the YJD group (p < 0.001), but fewer Bacteroides, unspecified Clostridiales and Coprococcus eutactus (p < 0.01). These differences might be at least in part explained by the higher concentrations of monosaccharide, palmitoleic acid, and glutamine synthetase adenyltransferase in the SSN product (p < 0.05), which were positively associated with F. prausnitzii (p ≤ 0.001) and B. longum (p < 0.05), and negatively associated with C. eutactus (p < 0.01). The single strain of starter culture and lower content of polyunsaturated fatty acids (PUFA) in the SSN product were also related to the different changes of gut microbia, and the taxa F. prausnitzii, Bifidobacterium and B. longum were negatively associated with starter culture and PUFA (p < 0.01). These findings suggested that SSN is rich in prebiotic components and might be beneficial for healthy adults. Furthermore, bacterial taxa with potential health benefits could be encouraged through improving the formulation and technology used to produce the dairy products.

Postinfarction healing dynamics in the mechanically unloaded rat left ventricle.

The healing process is a key determinant for postinfarction left ventricular (LV) remodeling and the development of heart failure, which could be influenced by mechanical (pressure and/or volume) load. So far, limited information exists regarding an indepth characterization of the postinfarct healing process in the mechanically unloaded state. In the present work, we performed isogenic Lewis-to-Lewis rat abdominal heterotopic heart transplantation, which is characterized by hemodynamic unloading in the left ventricle, and simultaneously ligated the left anterior descending coronary artery (T-infarct group). Pathological evolution was dynamically compared with that of in situ infarcted Lewis hearts (I-infarct group) on days 3, 7, 14, and 35. There was a remarkable myocardial salvage in the unloaded heart, as shown by the improvement in infarct size (T-infarct group: 25.47% ± 4.31% vs. I-infarct group: 38.46% ± 4.82%, P < 0.01) and the smaller fraction of fibrosis in infarct segments (T-infarct group: 42.12% ± 8.40% vs. I-infarct group: 75.65% ± 10.51%, P < 0.01). In addition, there was a progressive disorganization of the two-dimensional collagen fiber alignment as well as retarded collagen fiber maturation in the T-infarct group. We also observed enhanced angiogenesis, lymphangiogenesis, and inflammatory cell retention in the infarct region during mechanical unloading. Moreover, capillary density and collagen deposition were significantly increased in the noninfarcted area of the unloaded heart compared with the same region in the in situ infarcted heart. In conclusion, ischemic insult in the mechanically unloaded heart elicits an altered inflammatory and healing response, which is characterized by myocardial salvage, delayed resolution of inflammation, and disorganization of the collagen orientation in the infarcted region. These findings could provide novel insights into the contribution of hemodynamic load in the postinfarction healing process. Further studies are warranted to elucidate its potential mechanism.

Disassociation between left ventricular mechanical and electrical properties in ischemic rat heart after G-CSF treatment.

OBJECTIVE: The effect of granulocyte colony-stimulating factor (G-CSF) on post-infarct ventricular remodeling remains controversial. We hypothesized that the timing of G-CSF administration after myocardial ischemia plays an important role in determining its efficacy. METHODS: Rat myocardial ischemia was induced by 60 min coronary ligation and reperfusion. Surviving animals received G-CSF after 1 h (E-G) or 24 h (D-G) of reperfusion randomly at 100 µg/kg/d for five consecutive days. 7 days or 3 months post-ischemia, rat hearts were quickly removed for ex vivo electrophysiological measurements or histological analysis (collagen disposition and angiogenesis) and metalloproteinase-2 and -9 activity assays (gelatin zymography). Left ventricular (LV) invasive hemodynamic analysis was performed in 3-month recovery animals before sacrifice. RESULTS: At 3 months post ischemia, LV mechanical remodeling was further impaired with early G-CSF administration (0.65 ± 0.17%, 13.21 ± 7.36 mmHg, -4,684 ± 1,560 mmHg/s) compared with the control group (0.28 ± 0.12%, 6.45 ± 3.43 mmHg, -6,267 ± 1,111 mmHg/s) and D-G group (0.34 ± 0.12%, 7.90 ± 5.33 mmHg, -6,227 ± 1,075 mmHg/s) as shown by increased expansion index (P < 0.01), deterioration of myocardial function with increased LVDP (P < 0.05), and decreased -dP/dt (max) (P < 0.05). By contrast, there was a significant increase in electrical properties including monophasic action potential (MAP) 90 dispersion (12.58 ± 4.46 vs. 30.56 ± 6.17 ms at 7 days; 18.54 ± 4.31 vs. 34.78 ± 5.24 ms at 3 months; P < 0.05 for both) and inducibility of ventricular arrhythmias (4.78 ± 1.19 vs. 11.58 ± 2.76 ms at 3 months; P < 0.05) with early G-CSF treatment compared with the control group. CONCLUSIONS: Both early and delayed administrations of G-CSF can improve electrophysiological properties after myocardial ischemia, but have no beneficial effects on LV mechanical remodeling.

High salt intake accelerated cardiac remodeling in spontaneously hypertensive rats: time window of left ventricular functional transition and its relation to salt-loading doses.

Salt-loading is an accelerator of hypertensive left ventricular (LV) remodeling. The relationship between salt-loading doses and the time window in which a transition from compensated to decompensated LV hypertrophy occurs in spontaneously hypertensive rats (SHR) is unclear. Eight-week-old male SHR and Wistar Kyoto rats (WKY) were randomized to receive normal (0.5% NaCl) and high salt diets (4% or 8% NaCl) for 12 weeks. Left ventricular remodeling was dynamically determined by echocardiography. LV invasive hemodynamics and morphologic staining [collagen deposition, cardiomyocte hypertrophy, DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG) and apoptosis] were performed at time of sacrifice. Cardiac malonyldialdehyde (MDA) level was measured by ELISA. No differences between 4% and 8% salt diets, in terms of blood pressure (BP) levels, heart mass index, and myocardial fibrosis were observed either in SHR or in WKY. In high salt-loaded SHR, the LV ejection fraction and wall thickness peaked at 8 weeks after salt-loading, parallel with a progressive enlargement of the LV chamber size. Furthermore, when compared to 4% salt SHR, LV functions were significantly compromised in 8% salt SHR, accompanied by more prominent cardiomyoctye hypertrophy, oxidative stress (and related DNA damage), and apoptosis. Salt-loading for 12 weeks with 8% NaCl diet is more efficient to induce LV dysfunction than 4% NaCl diet does in SHR, possibly by initiating increased oxidative stress and resultant cardiac damage. Moreover, 8 to 12 weeks after 8% salt-loading is the key time window in which a transition from compensated to decompensated LV hypertrophy occurs.

[Benefits of placing intra-aortic vacant guide wire on interventional treatment of aorto-ostial lesions].

OBJECTIVE: To evaluate the potential benefits of placing intra-aortic vacant guide wire on interventional treatment of aorto-ostial lesions. METHODS: A total of 86 consecutive patients underwent percutaneous coronary interventions (PCI) for aorto-ostial lesions were randomly divided into conventional treatment group (group A) and intra-aortic vacant guide wire group (group B). Standard PCI techniques were applied in group A and an intra-aortic vacant guide wire was placed outside the guiding catheter before the guiding catheter into the target coronary artery in group B on basis of standard PCI techniques. The number of guiding catheter, guide wire, X-ray exposure time, total PCI time, the incidence of pressure drop and malignant arrhythmia, contrast agent dose and the number of failure cases were compared between the two groups. RESULTS: The number of used guide wire was similar between the groups (2.0 ± 1.1 vs. 2.2 ± 0.4, P > 0.05) and the number of guiding catheter used was significantly more in group A than in group B (2.3 ± 1.1 vs. 1.3 ± 0.5, P < 0.01). The X-ray exposure time (18.8 min ± 6.9 min vs. 14.2 min ± 5.7 min, P < 0.01) was significantly less in groups B and the total PCI time (31.2 min ± 8.1 min vs. 20.1 min ± 4.5 min, P < 0.01) and the amount of contrast agent (193.5 ml ± 25.4 ml vs. 130.6 ml ± 32.8 ml, P < 0.01) and the frequency of pressure drop (19 cases vs. 2 cases, P < 0.01) were all significantly higher in group A than in group B. Incidence of malignant ventricular arrhythmia (8 vs. 0) and procedure failure (6 vs. 0) was also higher in group A compared to group B. CONCLUSION: The method of using Intra-aortic vacant guide wire is associated with reduced risk and improved success rate of PCI for aorto-ostial lesions.

A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch: a prospective multicenter ranDomized (BEYOND) clinical trial in China.

BACKGROUND: Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions. METHODS: Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses. RESULTS: At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ±â€Š19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, Psuperiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ±â€Š0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group. CONCLUSIONS: In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov.