CX3CR1 deficiency promotes resolution of hepatic ischemia-reperfusion injury by regulating homeostatic function of liver infiltrating macrophages.

Hepatic ischemia-reperfusion injury(HIRI) remains to be an unsolved risk factor that contributes to organ failure after liver surgery. Our clinical retrospective study showed that lower donor liver CX3-C chemokine receptor-1(CX3CR1) mRNA expression level were correlated with upregulated pro-resolved macrophage receptor MERTK, as well as promoted restoration efficiency of allograft injury in liver transplant. To further characterize roles of CX3CR1 in regulating resolution of HIRI, we employed murine liver partial warm ischemia-reperfusion model by Wt & Cx3cr1-/- mice and the reperfusion time was prolonged from 6 h to 4-7 days. Kupffer cells(KCs) were depleted by clodronate liposome(CL) in advance to focus on infiltrating macrophages, and repopulation kinetics were determined by FACS, IF and RNA-Seq. CX3CR1 antagonist AZD8797 was injected i.p. to interrogate potential pharmacological therapeutic strategies. In vitro primary bone marrow macrophages(BMMs) culture by LXR agonist DMHCA, as well as molecular and functional studies, were undertaken to dissect roles of CX3CR1 in modulating macrophages cytobiological development and resolutive functions. We observed that deficiency or pharmacological inhibition of CX3CR1 facilitated HIRI resolution via promoted macrophages migration in CCR1/CCR5 manner, as well as enhanced MerTK-mediated efferocytosis. Our study demonstrated the critical roles of CX3CR1 in progression of HIRI and identified it as a potential therapeutic target in clinical liver transplantation.

Resting-state functional connectivity of social brain regions predicts motivated dishonesty.

Motivated dishonesty is a typical social behavior varying from person to person. Resting-state fMRI (rsfMRI) is capable of identifying unique patterns from functional connectivity (FC) between brain regions. Recent work has built a link between brain networks in resting state to dishonesty in Western participants. To determine and reproduce the relevant neural patterns and build an interpretable model to predict dishonesty, we analyzed two conceptually similar datasets containing rsfMRI data with different dishonesty tasks. Both tasks implemented the information-passing paradigm, in which monetary rewards were employed to induce dishonesty. We applied connectome-based predictive modeling (CPM) to build a model among FC within and between four social brain networks (reward, self-referential, moral, and cognitive control). The CPM analysis indicated that FCs of social brain networks are predictive of dishonesty rate, especially FCs within reward network, and between self-referential and cognitive control networks. Our study offers an conceptual replication with integrated model to predict dishonesty with rsfMRI, and the results suggest that frequent motivated dishonest decisions may require the higher engagement of social brain regions.

Metabolic profiling of ligustilide and identification of the metabolite in rat and human hepatocytes by liquid chromatography combined with high-resolution mass spectrometry.

Ligustilide is one of the most abundant bioactive ingredients in Rhizoma Chuanxiong that has been widely prescribed for medicinal purposes in China. To better understand the disposition and action of ligustilide, it is necessary to investigate the metabolic profiles. The in vitro metabolism was elucidated through incubating ligustilide with human and rat hepatocytes at 37°C. The incubation samples were collected at predefined time points to determine the metabolic stability. Upon metabolite identification and profiling, the incubation samples were analyzed by ultra-high-performance liquid chromatography combined with diode array detector and high-resolution mass spectrometry. The structures of the metabolites were characterized based on their mass spectrometry spectra, tandem mass spectrometry spectra, and fragmentation patterns. Ligustilide showed fast metabolism with high intrinsic clearance both in rat and human hepatocyte incubations. The half-lives of ligustilide in rat and human hepatocyte incubations were 8.0 and 15.0 min, respectively. Most of the parent (>90%) was biotransformed into the metabolites. Among these metabolites, M1 (senkyunolide I) was the major metabolite both in rat and human hepatocytes with the percentage of 42 and 70%, respectively. The metabolic pathways of ligustilide included epoxidation, epoxide hydrolysis, aromatization, hydroxylation, and glutathionylation. This work provided an overview of the metabolic profiles of ligustilide, which would be helpful for us to understand the action of this compound.

Gadolinium-hyaluronic acid nanoparticles as an efficient and safe magnetic resonance imaging contrast agent for articular cartilage injury detection.

Accurate detection of cartilage injuries is critical for their proper treatment because these injuries lack the self-healing ability and lead to joint dysfunction. However, the low longitudinal T1 relaxivity (r1) and non-specificity of contrast agents (such as gadolinium(III)-diethylenetriamine-pentaacetic acid (Gd-DTPA)) significantly limit the efficiency of clinical magnetic resonance imaging (MRI) applications. To overcome these drawbacks, we integrated hyaluronic acid (HA) with Gd to synthesize a Gd-DTPA-HA composite, which was subsequently freeze-dried to produce nanoparticles (NPs). The resultant Gd-HA NPs demonstrated a greater r1 value (12.51 mM-1 s-1) compared with the bulk Gd-DTPA-HA (8.37 mM-1 s-1) and clinically used Gd-DTPA (3.88 mM-1 s-1). Moreover, the high affinity of HA to the cartilage allowed these NPs to penetrate deeper beyond the cartilage surface. As a result, Gd-HA NPs considerably increased the quality of cartilage and lesion MR images via their intra-articular injection in vivo. Specifically, 2 h after NP administration, the signal-to-noise ratio at the injured cartilage site was 2.3 times greater than the value measured before the injection. In addition, Gd-HA NPs exhibited good biosafety properties due to the absence of adverse effects in the blood or on the main organs. It was also showed that Gd NPs were first metabolized by the kidney and liver and then excreted from the body with urine. Thus, Gd-HA NPs can potentially serve as an efficient MRI contrast agent for improved detection of cartilage injuries.

Overseeing health care facilities in Shanghai, China: regulatory regime, activities and challenges of the governmental regulatory system.

BACKGROUND: Government regulation has played a crucial role in ensuring the quality, safety and equity of health care. However, few empirical studies have investigated Chinese governmental oversight of health care facilities in terms of regulatory arrangements and approaches. This study aims to explore the regulatory regime and main activities within the health sector in Shanghai, a city featuring abundant health care resources and a complex medical system, to provide policy implications for better regulation and offer valuable reference for elsewhere in China and other developing countries. METHODS: We explored the structure and main activities of government regulation over health care facilities in Shanghai, compared it with the regulatory system in Hong Kong and Taipei through a literature review and analyzed the data on regulatory activities conducted by the local Health Supervision Agencies using descriptive statistical analysis. The data were collected from the Shanghai Statistical Yearbook 2014-2018 and the centralized data bank of the Shanghai Health Supervision Authority. RESULTS: Shanghai has established a unique governmental regulatory system compared to Hong Kong and Taipei. We found health care facilities in Shanghai underwent less frequent inspections between 2013 and 2017, as average annual inspections at individual facilities decreased from 3.8 to 2.7. The number of annual administrative penalties and notifications issued for accumulating points on local health care facilities' violations decreased by 24.8 and 40.7%, respectively, and complaints against health care facilities decreased by 29.1% during the study period. CONCLUSIONS: The local governmental regulatory system played a vital role in overseeing the health care facilities and ensuring their legal compliance by exerting the various regulatory activities. Both annual administrative penalties and notifications of accumulating points on local health care facilities' violations decreased considerably, with complaints against health care facilities reducing. As our study identified significant challenges, including regulatory fragmentation and no risk-based approach used, we offer recommendations to develop new policies and establish new mechanisms for better regulation.

[Dynamic changes of brain natriuretic peptide concentration and its diagnostic value for heart failure in early phase of acute myocardial infarction].

OBJECTIVE: To explore the dynamic changes in brain natriuretic peptide (BNP) concentration and the diagnostic value of BNP for heart failure at different time points in the early phase of acute myocardial infarction (AMI). METHODS: AMI patients who were admitted in our department between January 1, 2016 and July 31, 2016 and underwent emergency percutaneous coronary intervention (PCI) within 12 h after onset were enrolled in this study. All the patients received bedside examinations of BNP concentration and clinical cardiac function within 1 h after PCI and at 12, 20, 24 and 48 h after the onset of AMI. According to the peak BNP concentration, the patients were divided into high peak BNP group (> 400 pg/mL) and normal peak BNP group (≤400 pg/mL). RESULTS: Seventy patients were enrolled in the study. Within 48 h after AMI onset, BNP concentration variations followed a pattern of an initial increase till reaching the peak concentration at 20 to 24 h, with subsequent gradual decrease. BNP concentrations differed significantly among the indicated time points (χ2=141.7, P < 0.05) except for those between 20 h and 24 h (χ2=0.173, P > 0.05). Compared with those in normal peak BNP group, the patients in high peak BNP group had an older age, a lower BMI, a longer time to perfusion, and a higher likeliness of anterior myocardial infarction and pulmonary infection (P < 0.05). Logistic regression analysis showed that age, BMI and anterior myocardial infarction were independently associated with the increase of peak BNP concentration. ROC curve analysis showed that BNP concentration within 1 h after emergency PCI was unable to diagnose heart failure at that time (P > 0.05), while BNP concentrations at 12, 20, 24 and 48 h after AMI onset had significant diagnostic values for heart failure (P < 0.05) with areas under ROC of 0.860, 0.786, 0.768 and 0.863, and optimal cutoff values of 156.5, 313.7, 240.9 and 285.9 pg/mL, respectively. CONCLUSIONS: BNP concentration increases first and then decreases in the early phase of AMI, and the peak concentration occurs at 20-24 h after the onset. The diagnostic values of BNP concentrations at different time points also vary.

Value of three-dimensional strain parameters for predicting left ventricular remodeling after ST-elevation myocardial infarction.

This study was to evaluate the value of multi-directional strain parameters derived from three-dimensional (3D) speckle tracking echocardiography (STE) for predicting left ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) compared with that of two-dimensional (2D) global longitudinal strain (GLS). A total of 110 patients (mean age, 54 ± 9 years) after STEMI treated with primary PCI were enrolled in our study. At baseline (within 24 h after PCI), standard 2D echocardiography, 2D STE and 3D STE were performed to acquire the conventional echocardiographic parameters and strain parameters. At 3-month follow-up, standard 2D echocardiography was repeated to all the patients to determine LV remodeling, which was defined as a 20% increase in LV end-diastolic volume. At 3-month follow-up, LV remodeling occurred in 26 patients (24%). Compared with patients without LV remodeling, patients with remodeling had significantly reduced 2D GLS (-12.5 ± 3.2% vs -15.0 ± 3.1%, p < 0.001), 3D GLS (-9.9 ± 2.2% vs -13.1 ± 2.7%, p < 0.001), 3D global area strain (GAS) (-20.3 ± 3.9% vs -23.3 ± 4.8%, p = 0.005) and 3D global radial strain (GRS) (29.0 ± 7.4% vs 34.3 ± 8.5%, p = 0.007) at baseline, but there is no significant difference in 3D global circumferential strain (GCS) (-12.7 ± 2.9% vs -13.0 ± 3.2%, p = 0.822). Separated multivariate analysis shows that 2D GLS, 3D GLS, 3D GAS and 3D GRS all can be independent predictors of LV remodeling. However, receiver-operating characteristic curve analysis showed that the area under the curve of 3D GLS (0.82) for predicting LV remodeling was significantly higher than that of 2D GLS (0.72, p = 0.034), 3D GAS (0.68, p < 0.001) and 3D GRS (0.68, p < 0.001). In patients after STEMI, 2D GLS, 3D GLS, 3D GAS and 3D GRS but not 3D GCS measured after primary PCI are independent predictors of LV remodeling and 3D GLS is the most powerful predictor among them.

Biodegradation of tetrachlorothylene using methanol as co-metabolic substrate.

OBJECTIVE: To investigate the biodegradation of tetrachloroethylene (PCE) using methanol as electron donor by acclimated anaerobic sludge. METHODS: HP-6890 gas chromatograph (GC), together with HP-7694 autosampler, was used to analyze the concentration of PCE and intermediates. RESULTS: PCE could be decholrinated reductively to DCE via TCE, and probably further to VC and ethylene. The degradation of PCE and TCE conformed to first-order reaction kinetics. The reaction rate constants were 0.8991 d(-1) and 0.068 d(-1), respectively, and the corresponding half-life were 0.77 d and 10.19 d, respectively. TCE production rate constant was 0.1333 d(-1), showing that PCE was degraded more rapidly than TCE. CONCLUSION: Methanol is an electron donor suitable for PCE degradation and the cometabolic electron donors are not limiting factors for PCE degradation.

Anaerobic degradation of tetrachloroethylene using different co-substrates as electron donors.

OBJECTIVE: To investigate the biodegradation of tetrachloroethylene (PCE) by acclimated anaerobic sludge using different co-substrates, i.e., glucose, acetate, and lactate as electron donors. METHODS: HP-6890 gas chromatograph (GC) in combination with auto-sampler was used to analyze the concentration of PCE and its intermediates. Results PCE could be degraded by reductive dechlorination and the degradation reaction conformed to the first-order kinetic equation. The rate constants are k(lactate) > k(glucose) > k(acetate). The PCE degradation rate was the highest in the presence of lactate as an electron donor. CONCLUSION: Lactate is the most suitable electron donor for PCE degradation and the electron donors supplied by co-metabolic substrates are not the limiting factors for PCE degradation.

[Anaerobic biodegradation of tetrachloroethylene with methanol as co-metabolism substrate].

Tetrachloroethylene (PCE) is biodegraded by reductive dechlorination in anaerobic condition. PCE degradation by methanol as co-metabolism substrate was studied. Results show that PCE was dechlorinated reductively to DCEs and TCE, probable VC and ethene. DCEs, VC and ethene are probably end products. It also shows that PCE, TCE degradation and TCE production fit in first order kinetics. Reaction rate constants for PCE and TCE were 0.8991 d(-1) and 0.068 d(-1) respectively. Half-live were 0.77 d and 10.19 d respectively. TCE production rate constant was 0.1333 d(-1). Rate constants show that PCE is degraded more rapidly than TCE. Production rate of TCE is higher than degradation rate of TCE, so TCE exists through the experiment.