Short-Term Supraorbital Nerve Stimulation and Pain Relief for Acute and Subacute Ophthalmic Herpetic Neuralgia: A Randomized Controlled Crossover Trial.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is a kind of refractory disease, and treating it is important for preventing postherpetic neuralgia (PHN). But the evidence surrounding the current treatment options for these conditions is controversial, so exploring reasonable clinical treatment strategies for HZO is necessary. Neuromodulation is an excellent modality for the treatment of various neuropathic pain conditions. This trial was designed to evaluate the effectiveness of short-term supraorbital nerve stimulation (SNS) and the supraorbital nerve block (SNB) for HZO. OBJECTIVES: To determine whether short-term SNS relieves acute and subacute ophthalmic herpetic neuralgia. STUDY DESIGN: This prospective randomized controlled crossover trial compared short-term SNS to SNB. SETTING: The operating room of a pain clinic. METHODS: Patients with acute or subacute ophthalmic herpetic neuralgia were recruited. The patients were randomly assigned to receive either SNS or SNB. The primary outcome being measured was each patient's Visual Analog Scale (VAS) score at 4 weeks. The secondary outcomes under measurement were the proportion of patients who achieved ≥ 50% pain relief, sleep quality, medicine consumption, and adverse events. Crossover after 4 weeks was permitted, and patients were followed up to 12 weeks. RESULTS: Overall, 50 patients were included (n = 25/group). At 4 weeks, the patients who received SNS achieved greater pain relief, as indicated by their significantly different VAS scores from those of the SNB group (mean difference: -1.4 [95% CI, -2.29 to -0.51], P < 0.05). Both groups showed a significant decrease in pain level from the baseline (all P < 0.05). Overall, 72% and 44% of the SNS and SNB patients experienced ≥ 50% pain relief, respectively (OR: 0.31 [95% CI, 0.09 to 0.99], P < 0.05), and 68% and 32% of SNS and SNB patients, respectively, had VAS scores < 3 (OR: 0.22 [95% CI, 0.07 to 0.73], P < 0.05). Compared to the SNB group, the SNS group had better sleep quality, lower ophthalmic neuralgia, a lower proportion of further treatment, and lower analgesic intake. Overall, 18 patients received SNS alone, and 16 patients crossed over from SNB to SNS. The VAS scores, sleep quality, ophthalmic neuralgia, and trend of medicine intake were not significantly different between the groups (all P > 0.05). No serious complications occurred. LIMITATIONS: This study was nonblind. CONCLUSIONS: Short-term SNS is effective for controlling acute or subacute ophthalmic herpetic neuralgia. Combining SNS with SNB yields no additional benefits.

Tubuloside B, a major constituent of Cistanche deserticola, inhibits migration of hepatocellular carcinoma by inhibiting Hippo-YAP pathway.

BACKGROUND: Studies have shown that phenylethanoid glycosides (PhGs) have multiple pharmacological effects such as anti-inflammatory, hepatoprotective or neuroprotective functions, whereas their anti-tumor effects are rarely studied. Tubuloside B (Tub B) is a PhG isolated from Cistanche deserticola, a traditional Chinese medicine. To date, there is a lack of comprehensive research regarding the biological activity of Tub B. PURPOSE: The subject of the current study was to investigate the anti-hepatocellular carcinoma (HCC) cell activity and the underlying mechanism of Tub B. METHODS: We evaluated the in vitro anti-migratory effect of Tub B by scratch and transwell assays. RNA-seq was employed to identify the differential genes by Tub B. Besides, the functional mechanism of Tub B was investigated by distinct molecular biology techniques including immunofluorescent staining, quantitative PCR, as well as western blot analysis. Subsequently, we utilized Hep3B cells for in vivo metastasis assays through spleen injection and evaluated the anti-migratory effect of Tub B in hepatocellular carcinoma (HCC). RESULTS: Tub B exhibited in vitro and in vivo inhibition of HCC cell migration. Tub B decreased the expression of transcriptional target genes downstream of the Hippo pathway, including CTGF, CYR61, and N-cadherin as determined by RNA-seq. Furthermore, mechanistic studies confirmed that Tub B increased phosphorylation of YAP at S127, which contributes to YAP cytoplasmic localization. Additionally, overexpression of YAP abrogated Tub B-induced inhibition of HCC migration and the mRNA levels of CTGF, CYR61, and N-cadherin. CONCLUSIONS: Taken together, these results illustrated that Tub B demonstrated great potential in inhibiting migration of HCC, and a portion of its impact can be attributed to the modulation of the Hippo-YAP pathway.

Clay minerals/sodium alginate/polyethylene hydrogel adsorbents control the selective adsorption and reduction of uranium: Experimental optimization and Monte Carlo simulation study.

Clay minerals formations are potential geological barrier (host rocks) for the long-rerm storage of uranium tailing in deep geological repositories. However, there are still obstacles to the efficient retardation of uranium because of the competition between negatively charged regions at the clay minerals end face, surface and between layers, as well as low mineralization capacity. Herein, employing a simple method, we used sodium alginate (SA), an inexpensive natural polymer material, polyethylene (PE), and the natural clay minerals montmorillonite (Mt), nontronite (Nt), and beidellite (Bd) to prepare three hydrogel adsorbents, (denoted as Mt/PE-@SA, Nt/PE-@SA, and Bd/PE-@SA), respectively. The application of obtained hydrogel adsorbents further extends to uranium(VI) removal from aqueous. Due to the synergistic action of SA group and PE group, hydrogel adsorbents showed select adsorption and mineralization effect on uranium(VI), among which the maximum uranium(VI) adsorption capacity of Nt/PE-@SA was 133.3 mg·g-1 and Mt/PE-@SA exhibited strong selectivity for uranium(VI) in the presence of coexisting metal ions. Cyclic voltammetry studies indicated the mitigation and immobilization of uranium species onto adsorbents by both reduction and mineralization. Besides, the synergistic adsorption of SA and PE on clay minerals was hypothesized, and the idea was supported by structure optimizations results from Monte Carlo dynamics simulation (MCD). Three obtained hydrogel adsorbents structural model was constructed based on its physicochemical characterization, the low energy adsorption sites and adsorption energies are investigated using MCD simulation. The simulation results show that obtained hydrogel adsorbents have a strong interaction with uranium(VI), which ensures the high adsorption capacity of those materials. Most importantly, this work demonstrates a new strategy for preparing mineral-based hydrogel adsorbents with enough stability and provides a new perspective for uranium(VI) removal in complex environment.

Aucubin alleviates doxorubicin-induced cardiotoxicity through crosstalk between NRF2 and HIPK2 mediating autophagy and apoptosis.

BACKGROUND: Doxorubicin (DOX) is widely used for the treatment of a variety of cancers. However, its clinical application is limited by dose-dependent cardiotoxicity. Recent findings demonstrated that autophagy inhibition and apoptosis of cardiomyocytes induced by oxidative stress dominate the pathophysiology of DOX-induced cardiotoxicity (DIC), however, there are no potential molecules targeting on these. PURPOSE: This study aimed to explore whether aucubin (AU) acting on inimitable crosstalk between NRF2 and HIPK2 mediated the autophagy, oxidative stress, and apoptosis in DIC, and provide a new and alternative strategy for the treatment of DIC. METHODS AND RESULTS: We first demonstrated the protection of AU on cardiac structure and function in DIC mice manifested by increased EF and FS values, decreased serum CK-MB and LDH contents and well-aligned cardiac tissue in HE staining. Furthermore, AU alleviated DOX-induced myocardial oxidative stress, mitochondrial damage, apoptosis, and autophagy flux dysregulation in mice, as measured by decreased ROS, 8-OHdG, and TUNEL-positive cells in myocardial tissue, increased SOD and decreased MDA in serum, aligned mitochondria with reduced vacuoles, and increased autophagosomes. In vitro, AU alleviated DOX-induced oxidative stress, autophagy inhibition, and apoptosis by promoting NRF2 and HIPK2 expression. We also identified crosstalk between NRF2 and HIPK2 in DIC as documented by overexpression of NRF2 or HIPK2 reversed cellular oxidative stress, autophagy blocking, and apoptosis aggravated by HIPK2 or NRF2 siRNA, respectively. Simultaneously, AU promoted the expression and nuclear localization of NRF2 protein, which was reversed by HIPK2 siRNA, and AU raised the expression of HIPK2 protein as well, which was reversed by NRF2 siRNA. Crucially, AU did not affect the antitumor activity of DOX against MCF-7 and HepG2 cells, which made up for the shortcomings of previous anti-DIC drugs. CONCLUSION: These collective results innovatively documented that AU regulated the unique crosstalk between NRF2 and HIPK2 to coordinate oxidative stress, autophagy, and apoptosis against DIC without compromising the anti-tumor effect of DOX in vitro.

Exploring the Mechanism of Si-miao-yong-an Decoction in the Treatment of Coronary Heart Disease based on Network Pharmacology and Experimental Verification.

BACKGROUND: To investigate the active ingredients and the mechanisms of Si-miaoyong- an Decoction (SMYA) in the treatment of coronary heart disease (CHD) by using network pharmacology, molecular docking technology, and in vitro validation. METHODS: Through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Uniprot database, GeneCards database, and DAVID database, we explored the core compounds, core targets and signal pathways of the effective compounds of SMYA in the treatment of CHD. Molecular docking technology was applied to evaluate the interactions between active compounds and key targets. The hypoxia-reoxygenation H9C2 cell model was applied to carry out in vitro verification experiments. A total of 109 active ingredients and 242 potential targets were screened from SMYA. A total of 1491 CHD-related targets were retrieved through the Gene- Cards database and 155 overlapping CHD-related SMYA targets were obtained. PPI network topology analysis indicated that the core targets of SMYA in the treatment of CHD include interleukin- 6 (IL-6), tumor suppressor gene (TP53), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), phosphorylated protein kinase (AKT1) and mitogen-activated protein kinase (MAPK). KEGG enrichment analysis demonstrated that SMYA could regulate Pathways in cancer, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxiainducible factor-1(HIF-1) signaling pathway, VEGF signaling pathway, etc. Results: Molecular docking showed that quercetin had a significant binding activity with VEGFA and AKT1. In vitro studies verified that quercetin, the major effective component of SMYA, has a protective effect on the cell injury model of cardiomyocytes, partially by up-regulating expressions of phosphorylated AKT1 and VEGFA. CONCLUSION: SMYA has multiple components and treats CHD by acting on multiple targets. Quercetin is one of its key ingredients and may protect against CHD by regulating AKT/VEGFA pathway.

Phosphogypsum-Modified Vinasse Shell Biochar as a Novel Low-Cost Material for High-Efficiency Fluoride Removal.

In this study, vinasse shell biochar (VS) was easily modified with phosphogypsum to produce a low-cost and novel adsorbent (MVS) with excellent fluoride adsorption performance. The physicochemical features of the fabricated materials were studied in detail using SEM, EDS, BET, XRD, FTIR, and XPS techniques. The adsorption experiments demonstrated that the adsorption capacity of fluoride by MVS was greatly enhanced compared with VS, and the adsorption capacity increased with the pyrolysis temperature, dosage, and contact time. In comparison to chloride and nitrate ions, sulfate ions significantly affected adsorption capacity. The fluoride adsorption capacity increased first and then decreased with increasing pH in the range of 3-12. The fluoride adsorption could be perfectly fitted to the pseudo-second-order model. Adsorption isotherms matched Freundlich and Sips isotherm models well, giving 290.9 mg/g as the maximum adsorption capacity. Additionally, a thermodynamic analysis was indicative of spontaneous and endothermic processes. Based on characterization and experiment results, the plausible mechanism of fluoride adsorption onto MVS was proposed, mainly including electrostatic interactions, ion exchange, precipitation, and hydrogen bonds. This study showed that MVS could be used for the highly efficient removal of fluoride and was compatible with practical applications.

Prophylaxis with recombinant von Willebrand factor in patients with type 3 von Willebrand disease: Results of a post hoc analysis from a phase 3 trial.

OBJECTIVES: To describe efficacy/safety of recombinant von Willebrand factor (rVWF) prophylaxis in patients with type 3 von Willebrand disease (VWD). METHODS: This post hoc analysis of a phase 3 open-label trial provides a more detailed analysis of adults with type 3 VWD, categorized based on prior treatment at screening: "Prior On-Demand (OD)" (OD VWF; ≥3 documented spontaneous bleeding events [BEs] requiring VWF in previous 12 months) or "Switch" (plasma-derived [pd] VWF prophylaxis for ≥12 months). Annualized bleeding rates (ABRs) were evaluated during 12 months of rVWF prophylaxis versus historical data from medical records. RESULTS: In the Prior OD group (n = 10), mean spontaneous ABR (sABR) for treated BEs was reduced by 91.6% (ratio, 0.08; 95% CI, 0.02-0.45) versus mean historical sABR. In the Switch group (n = 8), mean sABR for treated BEs was reduced by 47% (ratio, 0.53; 95% CI, 0.08-3.62). One non-serious adverse event (AE) was considered possibly related to rVWF. No treatment-related, fatal, or life-threatening serious AEs were reported, and no patient developed VWF inhibitors. CONCLUSIONS: rVWF prophylaxis reduced sABR in type 3 VWD patients previously treated with OD VWF therapy, and maintained a similar level of hemostatic control in those switching from pdVWF prophylaxis to rVWF prophylaxis.

Orthostatic hypotension is associated with malnutrition diagnosed by GLIM in elderly hypertensive patients.

BACKGROUND: Orthostatic Hypotension (OH) and malnutrition, are common health problems in elderly hypertensive patients. This study aimed to analyze the relationship between malnutrition and OH in elderly hypertensive patients. METHODS: This is a cross-sectional single-center study. All participants underwent a Comprehensive Geriatric Assessment (CGA), in which malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria based on four different methods of diagnosing muscle mass loss. Furthermore, the accuracy of these methods was verified by Receiver Operating Characteristic (ROC) analysis. Univariate and multivariate logistic regression analyses were used to identify risk factors for OH in elderly hypertensive patients. RESULTS: For GLIM criteria, when Fat-Free Mass Index (FFMI) was the gold standard for muscle mass loss, the Area Under ROC Curve (AUC) values for Upper Arm Circumference (UAC), Calf Circumference (CC), and Hand Grip Strength (HGS) were 0.784, 0.805, and 0.832, with moderate accuracy in diagnosing malnutrition. Multivariate analysis showed that females, Diabetes Mellitus (DM), diuretics, and malnutrition diagnosed by GLIM-UAC were risk factors for OH in elderly hypertensive patients. CONCLUSION: Prompt detection of malnutrition in the elderly and attention to changes in UAC may be critical. Similarly, we should strengthen medication and disease management in elderly hypertensive patients.

Tanshinone I inhibits doxorubicin-induced cardiotoxicity by regulating Nrf2 signaling pathway.

BACKGROUND: Doxorubicin (DOX) is a powerful anti-tumor anthracycline drug. However, its clinical use is limited due to the side effect of cardiotoxicity. Tanshinone I (Tan I) is one of the major tanshinones isolated from Salvia miltiorrhiza. Studies have shown that Tan I is effective in the treatment of cardiovascular diseases. However, the potential effects of Tan I against DOX-induced cardiotoxicity (DIC) have yet to be explored. PURPOSE: This study aimed to explore whether Tan I can protect against DIC and to reveal whether Tan I can exert anti-oxidative effect by regulating nuclear erythroid factor 2-related factor 2 (Nrf2) pathway. METHODS: DIC models were established in vivo by intravenous injection of DOX. Echocardiography was used to monitor the cardiac function of mice. Transmission electron microscopy was used to assess mitochondrial damage. Oxidative stress was measured by dihydroethidium (DHE) staining and western blotting. The accumulation and nuclear translocation of Nrf2 was detected by immunofluorescence. H9C2 cellular DIC model was established in vitro to explore the pharmacological mechanism. Nrf2 small interfering (si)-RNA was applied to H9C2 cells to explore whether Tan I exerted protective effect against DIC through Nrf2 signaling pathway. The protective effects of Tan I on mitochondrial function and mitochondrial membrane permeability were measured by MitoSOX™ Red and JC-1 staining assays, respectively. RESULTS: In vivo experiments revealed that Tan I could improve cardiac function and protect against DOX-induced myocardial structural damages in mice models. The oxidative stress induced by DOX was suppressed and apoptosis was mitigated by Tan I treatment. Tan I protected against DOX-induced mitochondrial structural damage. Meanwhile, key proteins in Nrf2 pathways were upregulated by Tan I treatment. In vitro studies showed that Tan I attenuated DOX-induced generation of reactive oxygen species (ROS) in cultured H9C2 cells, reduced apoptotic rates, protected mitochondrial functions and up-regulated Nrf2 signaling pathway. Tan I promoted accumulation and nuclear translocation of Nrf2 protein. In addition, interference of Nrf2 abrogated the anti-oxidative effects of Tan I and reversed the expressions of key proteins in Nrf2 pathway. The protective effects of Tan I on mitochondrial integrity was also mitigated by Nrf2 interference. CONCLUSION: Tan I could reduce oxidative stress and protect against DIC through regulating Nrf2 signaling pathway. Nrf2 is a potential target and Tan I is a novel candidate agent for the treatment of DIC.

Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results.

International guidelines conditionally recommend long-term prophylaxis in patients with von Willebrand disease (VWD) and severe and frequent bleeding. As recombinant von Willebrand factor (rVWF; vonicog alfa) may reduce the frequency of treated spontaneous bleeding events (BEs), we investigated the efficacy and safety of rVWF prophylaxis in adults with severe VWD. Patients with BEs requiring VWF therapy in the past year (on-demand VWF therapy [prior on-demand group] or plasma-derived VWF prophylaxis [pdVWF; switch group]) were enrolled in a prospective, open-label, nonrandomized, phase 3 study. The planned duration of rVWF prophylaxis was 12 months; starting rVWF dose was 50 ± 10 VWF: ristocetin cofactor (VWF:RCo) IU/kg twice weekly (prior on-demand group) or based on prior pdVWF weekly dose/dosing frequency (switch group). The primary endpoint was annualized bleeding rate (ABR) of treated spontaneous BEs (sABR) during rVWF prophylaxis. Over the 12-month study period, treated sABR decreased by 91.5% on-study vs historical sABR in 13 patients in the prior on-demand group, and by 45.0% in 10 patients in the switch group (model-based analysis ratio, 0.085; 95% confidence interval [CI], 0.021-0.346 and 0.550; 95% CI, 0.086-3.523, respectively). No treated spontaneous BEs were recorded in 84.6% (11/13) and 70.0% (7/10) of patients, respectively. The safety profile of rVWF was consistent with the previously established profile, with no new adverse drug reactions identified. Findings suggest that rVWF prophylaxis can reduce treated spontaneous BEs in patients previously receiving on-demand VWF therapy and maintains at least the same level of hemostatic control in patients who switch from prophylaxis with pdVWF to rVWF, with a favorable safety profile. This trial was registered at www.clinicaltrials.gov (#NCT02973087) and www.clinicaltrialsregister.eu (#EudraCT 2016-001478-14).

Neurolytic Splanchnic Nerve Block and Pain Relief, Survival, and Quality of Life in Unresectable Pancreatic Cancer: A Randomized Controlled Trial.

BACKGROUND: Neurolytic splanchnic nerve block is used to manage pancreatic cancer pain. However, its impact on survival and quality of life remains controversial. The authors' primary hypothesis was that pain relief would be better with a nerve block. Secondarily, they hypothesized that analgesic use, survival, and quality of life might be affected. METHODS: This randomized, double-blind, parallel-armed trial was conducted in five Chinese centers. Eligible patients suffering from moderate to severe pain conditions were randomly assigned to receive splanchnic nerve block with either absolute alcohol (neurolysis) or normal saline (control). The primary outcome was pain relief measured on a visual analogue scale. Opioid consumption, survival, quality of life, and adverse effects were also documented. Analgesics were managed using a protocol common to all centers. Patients were followed up for 8 months or until death. RESULTS: Ninety-six patients (48 for each group) were included in the analysis. Pain relief with neurolysis was greater for the first 3 months (largest at the first month; mean difference, 0.7 [95% CI, 0.3 to 1.0]; adjusted P < 0.001) compared with placebo injection. Opioid consumption with neurolysis was lower for the first 5 months (largest at the first month; mean difference, 95.8 [95% CI, 67.4 to 124.1]; adjusted P < 0.001) compared with placebo injection. There was a significant difference in survival (hazard ratio, 1.56 [95% CI, 1.03 to 2.35]; P = 0.036) between groups. A significant reduction in survival in neurolysis was found for stage IV patients (hazard ratio, 1.94 [95% CI, 1.29 to 2.93]; P = 0.001), but not for stage III patients (hazard ratio, 1.08 [95% CI, 0.59 to 1.97]; P = 0.809). No differences in quality of life were observed. CONCLUSIONS: Neurolytic splanchnic nerve block appears to be an effective option for controlling pain and reducing opioid requirements in patients with unresectable pancreatic cancer.

The Impact of Intrinsic Capacity on Adverse Outcomes in Older Hospitalized Patients: A One-Year Follow-Up Study.

BACKGROUND: Intrinsic capacity (IC) is a novel view focusing on healthy aging. The effect of IC on adverse outcomes in older hospitalized Chinese adults is rarely studied. OBJECTIVES: This study focused on investigating the impact of IC domains on the adverse health outcomes including new activities of daily living (ADL) dependency, new instrumental activities of daily living (IADL) dependency, and mortality over a 1-year follow-up. METHODS: In a retrospective observational population-based study, a total of 329 older hospitalized patients from Zhejiang Hospital in China were enrolled and completed 1-year follow-up. The 5 domains of IC including cognition, locomotion, sensory, vitality, and psychological capacity were assessed at admission. The IC composite score was calculated based on these domains, and the higher IC composite score indicated the greater amount of functional capacities reserved. Multivariate logistic regression models were used to explore the association between IC at baseline and 1-year adverse outcomes. RESULTS: During the 1-year follow-up, 69 patients (22.5%) experienced new ADL dependency, 103 patients (33.6%) suffered from new IADL dependency, and 22 patients (6.7%) died. After adjusting for age, sex, education level, comorbidities, and polypharmacy, low Mini-Mental State Examination (MMSE) scores at admission predicted 1-year new ADL dependency (odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.12-4.78) and new IADL dependency (OR = 2.15, 95% CI: 1.14-4.04) among older hospitalized patients, but no significance was obtained between IC domains and mortality. Higher IC composite score at admission was associated with decreased risks of 1-year new ADL dependency (OR = 0.53, 95% CI: 0.40-0.70) and new IADL dependency (OR = 0.76, 95% CI: 0.61-0.95), and 1-year mortality (OR = 0.48, 95% CI: 0.31-0.74) after adjustment for the possible confounders. CONCLUSIONS: Loss of ICs at admission predicted adverse health outcomes including new ADL and IADL dependency and mortality 1 year after discharge among older hospitalized patients.

Index of microcirculatory resistance predicts long term cardiac systolic function in patients with STEMI undergoing primary PCI.

BACKGROUND: To evaluate the predictive value of the index of microcirculatory resistance (IMR) for long-term cardiac systolic function after primary percutaneous coronary intervention (pPCI) in patients with acute anterior wall ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 53 acute anterior wall STEMI patients were included and followed up within 1-year. IMR was measured to evaluate the immediate intraoperative reperfusion. IMR > 40 U was defined as the high IMR group and ≤ 40 U was defined as the low IMR group. Left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 h, 1 month, 3 months, and 1 year after PCI to analyze the correlation between IMR and cardiac systolic function. Heart failure was estimated according to classification within one year. RESULTS: The ratio of TMPG (TIMI myocardial perfusion grade) 3 (85.7% vs. 52%, p = 0.015) and STR (ST-segment resolution) > 70% (82.1% vs. 48%, p = 0.019) were significantly higher in the low IMR group. The LVEF in the low IMR group was significantly higher than that in the high IMR group at 3 months (43.06 ± 2.63% vs. 40.20 ± 2.67%, p < 0.001) and 1 year (44.16 ± 2.40% vs. 40.13 ± 3.48%, p < 0.001). IMR was negatively correlated with LVEF at 3 months (r = - 0.1014, p = 0.0040) and 1 year (r = - 0.1754, p < 0.0001). CONCLUSIONS: The IMR showed significant negative correlation with the LVEF value after primary PCI. The high IMR is a strong predictor of heart failure within 1 year after anterior myocardial infarction.

The diagnostic capability of electrocardiography on the cardiogenic shock in the patients with acute myocarditis.

BACKGROUND: The study was performed to assess the diagnostic capability of ECG on the cardiogenic shock (CS) in acute myocarditis. A new score was derived from the combination of the ECG parameters and the diagnostic value was also evaluated. METHODS: Total 103 consecutive patients with acute myocarditis admitted in Nanjing Drum Hospital were enrolled in the current study. The cohort was divided into fulminant myocarditis group (FM, n = 20) and non fulminant myocarditis group (NFM, n = 83). The demographic features, results of electrocardiography (ECG) and ultracardiography were compared. Logistic regression analysis was conducted to identify the relevant factors in ECG parameters. We created a new variable called "ECG score" by certain combination of ECG parameters. The diagnostic capability of ECG score for CS was compared with the existing diagnostic indices using regression model and receiver-operating characteristics (ROC) analysis. RESULTS: There were several changes on ECG significantly different between the two groups. Multivariate regression analysis demonstrated PR + QRS interval (P = 0.008), ventricular arrhythmia (P = 0.001) and pathological Q wave (P = 0.003) were the independent relevant factors of CS. The derived variable "ECG score" was identified as a significant relevant factor of CS by multivariate regression model. ROC analysis showed PR + QRS interval, ventricular arrhythmia and pathological Q wave all had equivalent diagnostic capability to left ventricular ejection fraction (LVEF) and shock index (SI). ECG score was equivalent to LVEF but superior to SI in diagnosing CS CONCLUSIONS: ECG was valuable in diagnosing CS due to acute myocarditis. The ECG score was superior to the traditional diagnostic indices and could be used for an rapid recognition of CS.

TREM2 Overexpression Attenuates Cognitive Deficits in Experimental Models of Vascular Dementia.

Neuroinflammation plays a prominent role in the pathogenesis of vascular dementia (VD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor mainly expressed on microglia and has been known for its anti-inflammatory properties during immune response. However, data evaluating the effects of TREM2 in VD are lacking. Therefore, the present study is aimed at investigating the role of TREM2 in VD. In this study, the mouse model of VD was induced by transient bilateral common carotid artery occlusion (BCCAO). We compared the hippocampal gene and protein expressions of TREM2 between the VD mice and sham-operated mice at different time points. The TREM2 mRNA and protein expression levels in the VD mice were higher than those in the sham-operated mice. The cognitive deficits of VD mice were observed in the Morris water maze test. Interestingly, overexpression of TREM2 by intracerebroventricular injection of a lentiviral vector that encoded TREM2 (LV-TREM2) significantly improved the spatial learning and memory and attenuated the hippocampal neural loss in VD mice. Further mechanistic study revealed that overexpression of TREM2 significantly inhibited microglia M1 polarization by decreasing inducible nitric oxide synthase (iNOS) and proinflammatory cytokines expression levels and conversely enhanced microglia M2 polarization by increasing Arginase-1 (Arg-1) and anti-inflammatory cytokine expression levels. These results strongly suggest that TREM2 provides a protective effect in VD via modulating the phenotype of activated microglia and may serve as a novel potential therapeutic target for VD.

Short-term and long-term outcomes of bailout versus planned coronary rotational atherectomy.

The goal of this study was to compare in-hospital and long-term events between bailout rotational atherectomy (RA) and planned RA. In this retrospective study, All patients who underwent percutaneous coronary intervention (PCI) using RA at Nanjing Drum Tower Hospital from November 2011 to December 2018 were enrolled in this study. Planned RA was defined as RA performed immediately before balloon pre-dilation, while bailout RA was defined as RA after failure to expand the balloon or perform any other procedure. In-hospital and long-term major adverse cardiac events (MACE, defined as cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR) and stroke) were compared between the two groups. After statistical analysis, a total of 211 patients underwent PCI with RA during the study period: 153 in the planned RA group, and 58 in the bailout group. The incidence of coronary dissection was significantly higher in the bailout RA group than in the planned RA group (22.4% vs. 6.5%, P = 0.001). However, no significant difference in in-hospital MACE was found between the two groups (12.1% vs. 13.7%, P = 0.752). There was no difference in all-cause mortality (9.1% vs. 12.5%, P = 0.504) or long-term MACE (13.8% vs. 17.1%, P = 0.560) between the groups. Bailout RA was associated with a significantly longer procedural time (139.86 ± 56.24 min vs. 105.56 ± 36.71 min, P < 0.001) than planned RA. Therefore, compared with bailout RA, planned RA is associated with shorter procedural time and reduced incidence of coronary dissection, with no difference in MACE or mortality.

Comparison of the prognosis for different onset stage of cardiogenic shock secondary to ST-segment elevation myocardial infarction.

OBJECTIVES: The study was conducted to evaluate the outcomes of different onset stage of cardiogenic shock (CS) in the patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Total 675 STEMI patients who had undergone primary percutaneous coronary intervention (pPCI) from November 2010 to December 2017 in Nanjing Drum Tower Hospital were enrolled. According to the onset time of CS, the cohort was divided into three groups: Non-CS group, CS on admission group and Developed CS group. The short-term (30 days), middle-term (12 months) and long-term (80 months) outcomes were analyzed. COX proportional hazard models were established for identification of the predictors. RESULTS: The all cause death, cardiac death and major adverse cardiac events (MACE) at 30 days were similar among the three groups. The incidence of MACE in the CS on admission group was significantly higher than the other two groups at 12 months. As to the long-term outcomes, the CS on admission group had lower survival rate than the other two groups. The Develop CS group had lower survival rate than Non-CS group numerically with a trend towards statistical significance. The incidence of cardiac death in the Non-CS group was the lowest. The incidence of MACE in the CS on admission group was much higher compared with the other two groups. After multivariate analysis, the independent predictors of all cause death included age, male sex, prior stroke and LVEF. The independent predictors of cardiac death included age, male sex, prior stroke, LVEF, CS on admission and developed CS. The independent predictors of MACE included age, prior stroke, LVEF, multivessel lesions, post-PCI TIMI grade 1 and CS on admission. CONCLUSIONS: The long-term outcomes of CS on admission group were the worst of all. The outcomes of Developed CS group laid between the other two groups. The consequences highlighted the importance of prevention for CS developing in the STEMI patients during hospitalization.

Global regulator engineering enhances bioelectricity generation in Pseudomonas aeruginosa-inoculated MFCs.

The electricigens with high-electroactivity is essential for resolving the low electricity power output (EPT) of microbial fuel cells (MFCs). However, the manipulation by single functional genes shows limitation because electroactivity is a complex phenotype controlled by multiple genes. Herein, global regulator engineering (GRE) was developed to optimize the electroactivity of an isolated strain (Pseudomonas aeruginosa P3-A-11) using an exogenous global regulator IrrE (ionizing radiation resistance E linkage group) as an object. The GRE was implemented through in vitro random mutagenesis by error-prone PCR and in vivo high-through screening comprised of cultures color assay, PYO measurement and MFCs operation. Four mutants with higher electroactivity were obtained, among which, the mutant 11/M2-59 not only displayed the maximal power density, but also exhibited stronger salt tolerance, consequently showing good performance of MFCs in the presence of salt. Apart from the reduced internal resistance, the increase in phenazines amounts primarily contributed to EPT improvement, which was realized by enhancing the core biosynthesis pathway and affecting other pathways (such as central metabolism pathway, quorum sensing system, regulatory network). Notably, IrrE exerted its positive effect on electroactivity even without native regulators (such as PmpR and RpoS). In addition, the significant fluctuations in expression levels of stress-responsive genes mediated by GRE were closely associated with the enhanced salt tolerance. This work demonstrated that GRE was an effective approach for simultaneously optimizing multiple phenotypes (such as electroactivity and stress tolerance), and thus would provide more opportunities to create high-efficiency electricigens and further promoted the practical application of MFCs.

Long non-coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis by targeting p53 following myocardial infarction.

Mounting evidence has indicated that long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) regulates cell apoptosis, and is involved in a variety of diseases. However, its exact role in myocardial infarction (MI) has not been fully elucidated. In the present study, we firstly observed that the expression levels of the lncRNA MEG3 in infarct hearts and hypoxic neonatal mice ventricular myocytes (NMVMs) were up-regulated by quantitative real-time PCR (qRT-PCR). Then, we knocked down lncRNA MEG3 by lentiviral delivery in the myocardial border region following multipoint injection. Following 28 days of MI, the lncRNA MEG3 knockdown mice indicated better cardiac function, and less cardiac remodelling by ultrasonic cardiogram and histological analysis. In addition, we indicated that lncRNA MEG3 knockdown reduced myocyte apoptosis and reactive oxygen species production in MI mice model and hypoxic NMVMs. Furthermore, we revealed that knockdown of lncRNA MEG3 protected against endoplasmic reticulum stress (ERS)-mediated myocardial apoptosis including the induction of PERK-eIF2α and caspase 12 pathways. At last, we provided evidence that p53 was identified as a protein target of lncRNA MEG3 to regulate NF-κB- and ERS-associated apoptosis. Taken collectively, our findings demonstrated that lncRNA MEG3 knockdown exerted cardioprotection by reducing ERS-mediated apoptosis through targeting p53 post-MI.