Ceftazidime-avibactam induced renal disorders: past and present.

With the increasing prevalence of multidrug-resistant Gram-negative bacterial pathogens worldwide, antimicrobial resistance has become a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) exhibited excellent in vitro activity against many carbapenemase-producing pathogens, and was widely used for the treatment of various complicated infections. CAZ-AVI is well tolerated across all dosing regimens, and its associated acute kidney injury (AKI) in phase II/III clinical trials is rare. However, recent real-world studies have demonstrated that CAZ-AVI associated AKI was more frequent in real-world than in phase II and III clinical trials, particularly in patients receiving concomitant nephrotoxic agents, with critically ill patients being at a higher risk. Herein, we reviewed the safety data related to renal impairment of CAZ-AVI, and discussed its pharmacokinetic/pharmacodynamic targets and dosage adjustment in patients with impaired renal function. This review aimed to emphasize the importance for healthcare professionals to be aware of this adverse event of CAZ-AVI and provide practical insights into the dosage optimization in critically ill patients with renal dysfunction.

Design and Synthesis of 6-amido-3-carboxypyridazine Derivatives as Potent T3SS Inhibitors of Salmonella Enterica Serovar Typhimurium.

BACKGROUND: Salmonella enterica (S. enterica) serovar Typhimurium, an anaerobic enteric pathogene, could cause human and animal diseases ranging from mild gastroenteritis to whole body serious infections. OBJECTIVE: The goal of this paper was to synthesize new 6-amido-3-carboxypyridazine derivatives with different lengths of side chains with the aim of getting potent antibacterial agents. METHODS: Synthesized compounds were analyzed by analytical techniques, such as 1H NMR, 13C NMR spectra, and mass spectrometry. We designed a series of novel 6-amido-3-carboxypyridazines using FA as the lead compound with the scaffold hopping strategy and their inhibitory activity against the effectors of type III secretion system (T3SS) using SDS-PAGE and western blot analysis for two rounds. Also, the preliminary mechanism of action of this series of compounds on T3SS was investigated using real-time qPCR. RESULTS: Nine 6-amido-3-carboxypyridazines were synthesized. The results of the inhibitory activities evaluated showed that compound 2i was the most potent T3SS inhibitor, which demonstrated potent inhibitory activities on the secretion of the T3SS SPI-1 effectors in a dose-dependent manner. Interestingly, the transcription of SPI-1 may be affected by compound 2i through the SicA/ InvF regulatory pathway. CONCLUSION: The novel synthetic 6-amido-3-carboxypyridazines could act as potent leads for the development of novel antibacterial agents.

Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS: In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

LZY3016, a novel geldanamycin derivative, inhibits tumor growth in an MDA-MB-231 xenograft model.

A novel geldanamycin derivative LZY3016 was synthesized as an antitumor agent. Compound LZY3016 exhibited potent anti-proliferation activity toward MDA-MB-231 (IC50 = 0.06 µM), which was more effective than positive drug 17-AAG. In vivo hepatotoxicity assay displayed that serum AST/ALT levels in LZY3016-treated mice were both significantly less than those in the geldanamycin (GA) group. LZY3016 showed potent antitumor activity in an MDA-MB-231 xenograft mouse model, suggesting LZY3016 is an up-and-coming antitumor candidate. The theoretical binding mode between LZY3016 and Hsp90 was obtained by molecular dynamics simulation.

An HPLC-MS/MS method for determination of sulbactam in human plasma and its pharmacokinetic application in critically ill patients with augmented renal clearance.

OBJECTIVE: A simple, rapid, and specific method has been developed and validated to measure sulbactam in human plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). MATERIALS AND METHODS: The pharmacokinetic characteristics of sulbactam in critically ill patients with augmented renal clearance were investigated after the repeated administration of cefoperazone-sulbactam (3 g, q8, IV drip, combination ratio of 2 : 1). Sulbactam plasma concentration was determined using LC-MS/MS with tazobactam used as an internal standard (IS). RESULTS: The method was fully validated with a sensitivity of 0.20 µg/mL, the linear concentration was ranged from 0.20 to 30.0 µg/mL. The intra-batch precision (RSD%) was less than 4.9%, and the accuracy deviation (RE%) ranged from -9.9 to 1.0%; the inter-batch precision (RSD%) was less than 6.2%, and the accuracy deviation (RE%) ranged from -9.2% to 3.7%. The value of the mean matrix factor at the low and high quality control (QC) concentration was 96.8 and 101.0%, respectively. The extraction recovery for QCL and QCH of sulbactam were 92.5 and 87.5%,respectively. Plasma samples and clinical data were collected at 0 (pre dose), 0.25, 0.5, 1, 2, 3, 6, and 8 hours (post dose) from 11 critically ill patients. Pharmacokinetic parameters were determined by non-compartmental analysis (NCA) using Phoenix WinNonlin software. CONCLUSION: This method was successfully applied to study the pharmacokinetics of sulbactam for critically ill patients. The main pharmacokinetic parameters of sulbactam in augmented renal function and normal renal function groups were summarized as follows: half-life, 1.45 ± 0.66 and 1.72 ± 0.58 hours, area under the concentration-time curve from 0 to 8 hours, 59.1 ± 20.1 and 111.4 ± 23.2 µg × h/mL, drug plasma clearance at steady state, 18.9 ± 7.5 and 9.32 ± 2 .03 L/h, respectively. These results suggested that a higher dose of sulbactam should be used in critically ill patients with augmented renal clearance.

The role of bile acids in regulating glucose and lipid metabolism.

In recent years, bile acids (BAs) are increasingly being appreciated as signaling molecules beyond their involvement in bile formation and fat absorption. The farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) are two dominating receptors through which BAs modulate glucose and lipid metabolism. FXR is highly expressed in the intestine and liver. GPBAR1 is highly expressed in the intestine. The present study reviews the metabolism and regulation of BAs, especially the effects of BAs on glucose and lipid metabolism by acting on FXR in the liver and intestine, and GPBAR1 in the intestine. Furthermore, it explains that fibroblast growth factor 15/19 (FGF15/19), ceramide, and glucagon like peptide-1 (GLP-1) are all involved in the signaling pathways by which BAs regulate glucose and lipid metabolism. This article aims to provide an overview of the molecular mechanisms by which BAs regulate glucose and lipid metabolism, and promote further scientific and clinical research on BAs.

Incidence, characteristics and risk factors of hypofibrinogenemia associated with tigecycline: A multicenter retrospective study in China.

Background: Tigecycline was recently found to cause coagulation disorders, especially hypofibrinogenemia, which may interfere with the administration of antimicrobial therapy. This study aimed to investigate the incidence and clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia. Methods: In this multicenter retrospective study, patients receiving tigecycline or imipenem-cilastatin to treat Gram-negative bacterial infections in nine Chinese tertiary hospitals between January 2020 and December 2020 were enrolled. Baseline data and coagulation variables were compared using cohort and case-control studies. Results: Totals of 485 patients treated with tigecycline and 490 patients treated with imipenem-cilastatin were included in this study. Compared with imipenem-cilastatin, tigecycline was associated with reduced fibrinogen and prolonged activated partial thromboplastin time and prothrombin time (all p < 0.001), with the most remarkable change in fibrinogen (down by 48.0%). The incidence of hypofibrinogenemia in patients treated with tigecycline was >50%, with propensity score-matched analysis or not. The relative risk of hypofibrinogenemia with tigecycline versus imipenem-cilastatin was 2.947 (95% CI: 2.151-4.039) at baseline balance. Tigecycline-associated hypofibrinogenemia led to a higher incidence (12.1%) of bleeding events. However, none of supplemental therapies after withdrawal had an effect on the normalization of fibrinogen levels. The risk factors for tigecycline-associated hypofibrinogenemia were treatment duration ≥6 days (odds ratio [OR] 5.214, 95% confidence interval [CI] 2.957-9.191, p < 0.001), baseline fibrinogen <4 g/L (OR 4.625, 95% CI 2.911-7.346, p < 0.001), cumulative dose ≥1,000 mg (OR 2.637, 95% CI 1.439-4.832, p = 0.002), receiving CRRT (OR 2.436, 95% CI 1.179-5.031, p = 0.016), baseline PT > 14 s (OR 2.110, 95% CI 1.317-3.380, p = 0.002) and baseline total bilirubin >21 µmol/L (OR 1.867, 95% CI 1.107-3.147, p = 0.019), while the protective factor was skin and soft tissue infection (OR 0.110, 95% CI 0.026-0.473, p = 0.003). Conclusion: The clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia identified in this study can offer practical reference for the clinical management of patients.

The Monte Carlo Simulation of Three Antimicrobials for Empiric Treatment of Adult Bloodstream Infections With Carbapenem-Resistant Enterobacterales in China.

Introduction: The aim of this study was to predict and evaluate three antimicrobials for treatment of adult bloodstream infections (BSI) with carbapenem-resistant Enterobacterales (CRE) in China, so as to optimize the clinical dosing regimen further. Methods: Antimicrobial susceptibility data of blood isolates were obtained from the Blood Bacterial Resistance Investigation Collaborative Systems in China. Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) of tigecycline, polymyxin B, and ceftazidime/avibactam against CRE. Results: For the results of PTAs, tigecycline following administration of 50 mg every 12 h, 75 mg every 12 h, and 100 mg every 12 h achieved > 90% PTAs when minimum inhibitory concentration (MIC) was 0.25, 0.5, and 0.5 µg/mL, respectively; polymyxin B following administration of all tested regimens achieved > 90% PTAs when MIC was 1 µg/mL with CRE; ceftazidime/avibactam following administration of 1.25 g every 8 h, 2.5 g every 8 h achieved > 90% PTAs when MIC was 4 µg/mL, 8 µg/mL with CRE, respectively. As for CFR values of three antimicrobials, ceftazidime/avibactam achieved the lowest CFR values. The highest CFR value of ceftazidime/avibactam was 77.42%. For tigecycline and ceftazidime/avibactam, with simulated regimens daily dosing increase, the CFR values were both increased; the highest CFR of tigecycline values was 91.88%. For polymyxin B, the most aggressive dosage of 1.5 mg/kg every 12 h could provide the highest CFR values (82.69%) against CRE. Conclusion: This study suggested that measurement of MICs and individualized therapy should be considered together to achieve the optimal drug exposure. In particular, pharmacokinetic and pharmacodynamic modeling based on local antimicrobial resistance data can provide valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.

Dose optimisation based on pharmacokinetic/pharmacodynamic target of tigecycline.

Tigecycline, a new first-in-class glycylcycline antibiotic, has shown promising efficacy against a broad range of micro-organisms. It is widely prescribed for various infections, with most prescriptions being considered for off-label use. However, only a few years after its approval by the US Food and Drug Administration (FDA), tigecycline is suspected of increasing all-cause mortality. Some clinicians have suggested such unfavourable outcomes correlate with inadequate drug exposure at the infection site. The pharmacokinetic/pharmacodynamic (PK/PD) profile of a drug plays an important role in predicting its antibiotic effect, which for tigecycline is determined as the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC). In this study, PK/PD targets based on infection sites, bacterial isolates and patient populations are discussed. Generally, a higher dosage of tigecycline for the treatment of serious infections has been recommended in previous reports. However, the latest finding of tigecycline's atypical protein binding property requires consideration when recommending further use. In addition, combination therapy with other antibiotics provides another option by potentially lowering the MICs of multidrug-resistant bacteria.

An overview of potential therapeutic agents to treat COVID-19.

The emerging novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has swept across the world and become a global threat to public health. More than 200 countries and territories worldwide are suffering from this COVID-19 pandemic. Worryingly, no specific vaccines or drugs have been approved for the prevention or treatment of COVID-19. Under the pressure of a sustained rise in the incidence and mortality of COVID-19, an unprecedented global effort is being implemented to identify effective drugs to combat the current coronavirus. As the understanding of SARS-CoV-2 virology, the underlying mechanism by which it attacks host cells, and the host response to the infection rapidly evolves, drugs are being repurposed and novel drugs are being identified and designed to target the SARS-CoV-2 pathogenesis. Presented here is a brief overview of both virus-based and host-based potential therapeutic drugs that are currently being investigated.

Research on Focal Length Measurement Scheme of Self-Collimating Optical Instrument Based on Double Grating.

In this paper, we propose a scheme for measuring the focal length of a collimating optical instrument. First, a mathematical model for measuring the focal length of a collimator with double gratings is derived based on the moiré fringe formula and the principles of geometric optics. Mathematical simulation shows that a slight difference in the focal length of two collimators has an important influence on the imaging law of moiré fringes. Our solution has a good resolution ability for focal length differences within 5‱, especially in the small angle range below 4°. Thus, the focal length of collimators can be measured by the amplification of the slight difference. Further, owing to the relative reference measurement, the measurement resolution at the symmetrical position of focal length is poor. Then, in the designed experiment, a corresponding moiré image at different angles is acquired using collimators with known focal length. The experimental results indicate that the root mean square error (RMSE) of the collimator corresponding to grating angles of 2°-4° is better than 4.7‱, indicating an ideal measurement accuracy of the proposed scheme. This work demonstrates that our proposed scheme can achieve an ideal accuracy in the measurement of a symmetrical optical path.

Design and synthesis of novel 2-arylbenzimidazoles as selective mutant isocitrate dehydrogenase 2 R140Q inhibitors.

A series of novel 2-arylbenzimidazoles have been designed, synthesized and evaluated for their inhibitory activity against IDH2 R140Q mutant. The preliminary results indicated that four compounds 7b, 7c, 7m and 7r displayed the potent inhibitory activity against IDH2 R140Q mutant. Among them, compound 7c showed the highest inhibitory activity, with the IC50 value of 0.26 µM, which was more active than positive control enasidenib. The exquisite selectivity of 7c for IDH2 R140Q mutant isoform was demonstrated by the poor activity against the IDH1 R132C mutant, IDH1 R132H mutant, wild-type IDH1, IDH2 R172K mutant and the wild-type IDH2.

Electrosprayed Polymeric Nanospheres for Enhanced Solubility, Dissolution Rate, Oral Bioavailability and Antihyperlipidemic Activity of Bezafibrate.

BACKGROUND: Bezafibrate is a BCS class II drug as it presents very low solubility in water; therefore, its bioavailability after oral administration is very poor. The aim of this work was to enhance solubility and dissolution rate of bezafibrate in water in order to enhance its oral bioavailability. METHODS: Several formulations were prepared using PVP K30 and Cremophor ELP employing the solvent-evaporation method and the electrospraying technique. Solubility, release rate, bioavailability in male Sprague Dawley rats, and lipid profile attributes in Wistar rats were assessed in comparison with bezafibrate plain powder. Solid-state characterization was carried out using X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). RESULTS: All the formulations exerted positive effect towards the desired goal. In particular, the optimized formulation furnished about 14-fold enhanced solubility and 85.48 ± 10.16% drug was released in 10 min as compared with bezafibrate alone (4.06 ± 2.59%). The drug existed in the amorphous state in the prepared sample as confirmed by XRD and DSC, whilst no drug-excipient interactions were observed through FTIR analysis. Moreover, SEM revealed smooth-surfaced spherical particles of the optimized formulation. A 5.5-fold higher oral bioavailability was achieved with the optimized formulation in comparison with bezafibrate plain powder. Also, TG, LDL and TC were decreased, and HDL was increased considerably in HFD-treated rats. CONCLUSION: The optimized formulation consisting of bezafibrate, PVP K30 and cremophor ELP (1/12/1.5, w/w/w) might be a capable drug delivery system for orally administering poorly water-soluble bezafibrate with improved bioavailability and antihyperlipidemic effects.

Liver dysfunction induced by Levothyroxine Sodium Tablets (Euthyrox®) in a hypothyroid patient with Hashimoto's thyroiditis: case report and literature review.

A 49-year-old woman with hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) (Euthyrox®) from 25 µg to 50 µg. Viral hepatitis, autoimmune hepatitis and non-alcoholic steatohepatitis (NASH) were ruled out with examinations. She had no concurrent medication and had no history of infectious, chronic or any other autoimmune diseases. After cessation of Levothyroxine Sodium Tablets (Euthyrox®), liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in "Diagnosis and treatment guideline on drug-induced liver injury" issued by the Chinese Medical Association (2015). As an alternative 25 µg qod of Levothyroxine Sodium Tablets (Letrox®) was tried and increased gradually up to 75 µg daily. Since then liver enzymes have remained within normal range. The main difference of additive for both tablets is whether it contains lactose or not: Euthyrox® contains lactose which caused no liver injury, thus excluding the possibility that an additive of Euthyrox® contributed to liver injury. The relatively quicker and larger replacement with synthetic T4 for hypothyroidism inducing transient thyrotoxicosis was suspected, although thyroid function was normal. Immune-mediated drug-induced liver injury (DILI) was also not excluded. This is a rare case of drug-induced liver injury due to levothyroxine tablets. It reminded us that when replacement with synthetic T4 for hypothyroidism is done, smaller-dose initiation and slower-speed increase may be useful for treatment of cases similar to genetically susceptible individuals.

Synthesis and biological evaluation of geldanamycin-ferulic acid conjugate as a potent Hsp90 inhibitor.

A novel geldanamycin-ferulic acid conjugate LZY228 was prepared and evaluated for anti-proliferation activity on human cancer cell line MDA-MB-231. Compound LZY228 exhibited potent cytotoxicity with IC50 value of 0.27 µM, which was more potent than 17-AAG. Hepatotoxicity test in mice demonstrated that the levels of both AST and ALT of LZY228-treated group were lower than that of GA-treated group, indicating that LZY228 was a promising antitumor candidate. In addition, excellent in vivo antitumor potency of LZY228 was observed in MDA-MB-231 xenograft model, which was superior to reference drug 17-AAG. Docking and MD refinement of the Hsp90-LZY228 complex give us an explanation of theoretical binding model of 17-ferulamido-17-demethoxygeldanamycins at molecular level.

Diagnosis-related group (DRG)-based case-mix funding system, a promising alternative for fee for service payment in China.

Fee for services (FFS) is the prevailing method of payment in most Chinese public hospitals. Under this retrospective payment system, medical care providers are paid based on medical services and tend to over-treat to maximize their income, thereby contributing to rising medical costs and uncontrollable health expenditures to a large extent. Payment reform needs to be promptly implemented to move to a prospective payment plan. The diagnosis-related group (DRG)-based case-mix payment system, with its superior efficiency and containment of costs, has garnered increased attention and it represents a promising alternative. This article briefly describes the DRG-based case-mix payment system, it comparatively analyzes differences between FFS and case-mix funding systems, and it describes the implementation of DRGs in China. China's social and economic conditions differ across regions, so establishment of a national payment standard will take time and involve difficulties. No single method of provider payment is perfect. Measures to monitor and minimize the negative ethical implications and unintended effects of a DRG-based case-mix payment system are essential to ensuring the lasting social benefits of payment reform in Chinese public hospitals.

Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway.

Increasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion (MI/R) diseases. In this study, we investigated whether Ginkgolide C (GC), a potent anti-inflammatory flavone, extenuated MI/R injury through inhibition of inflammation. In vivo, rats with the occlusion of the left anterior descending (LAD) coronary artery were applied to mimic MI/R injury. In vitro, primary cultured neonatal ventricular myocytes exposed to hypoxia/reoxygenation (H/R) were applied to further discuss the anti-H/R injury property of GC. The results revealed that GC significantly improved the symptoms of MI/R injury, as evidenced by reducing infarct size, preventing myofibrillar degeneration and reversing the mitochondria dysfunction. Moreover, histological analysis and Myeloperoxidase (MPO) activity measurement showed that GC remarkably suppressed Polymorphonuclears (PMNs) infiltration and ameliorated the histopathological damage. Furthermore, GC pretreatment was shown to improve H/R-induced ventricular myocytes viability and enhance tolerance of inflammatory insult, as evidenced by suppressing expression of CD40, translocation of NF-κB p65 subunit, phosphorylation of IκB-α, as well as the activity of IKK-ß. In addition, downstream inflammatory cytokines modulated by NF-κB signaling were effectively down-regulated both in vivo and in vitro, as determined by immunohistochemistry and ELISA. In conclusion, these results indicate that GC possesses a beneficial effect against MI/R injury via inflammation inhibition that may involve suppression of CD40-NF-κB signal pathway and downstream inflammatory cytokines expression, which may offer an alternative medication for MI/R diseases.

China's achievements and challenges in improving health insurance coverage.

China has undertaken waves of healthcare reforms to keep pace with its rapid economic growth. By 2011, universal health insurance coverage was successfully achieved through the creation of a basic social medical insurance system. Growing economic power, extensive government subsidies, and strategies for program implementation are critical to that achievement. However, the breadth and depth of coverage varies considerably across insurance schemes and localities. The disjointed insurance scheme led to inequality in coverage, accessibility, and affordability of medical services, lopsided allocation of health resources, and increasing medical expenditures, and these remain crucial challenges for healthcare insurance coverage. This paper describes societal conditions, polices, achievements and challenges in improving health insurance coverage in China. Thailand's experience in universal health insurance coverage and its implications for China's new medical reform are also discussed. Solutions including sustainable increases in government investment, transformation of payment methods, reinforcement of primary health care delivery and the referral system, and standardization of benefits packages are strongly recommended to address challenges in China's long-running medical reform.

Reflector automatic acquisition and pointing based on auto-collimation theodolite.

An auto-collimation theodolite (ACT) for reflector automatic acquisition and pointing is designed based on the principle of autocollimators and theodolites. First, the principle of auto-collimation and theodolites is reviewed, and then the coaxial ACT structure is developed. Subsequently, the acquisition and pointing strategies for reflector measurements are presented, which first quickly acquires the target over a wide range and then points the laser spot to the charge coupled device zero position. Finally, experiments are conducted to verify the acquisition and pointing performance, including the calibration of the ACT, the comparison of the acquisition mode and pointing mode, and the accuracy measurement in horizontal and vertical directions. In both directions, a measurement accuracy of ±3″ is achieved. The presented ACT is suitable for automatic pointing and monitoring the reflector over a small scanning area and can be used in a wide range of applications such as bridge structure monitoring and cooperative target aiming.

Cardioprotection of Ginkgolide B on Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Regulation of A20-NF-κB Pathway.

Inflammation urges most of the characteristics of plaques involved in the pathogenesis of myocardial ischemia/reperfusion injury (MI/RI). In addition, inflammatory signaling pathways not only mediate the properties of plaques that precipitate ischemia/reperfusion (I/R) but also influence the clinical consequences of the post-infarction remodeling and heart failure. Here, we studied whether Ginkgolide B (GB), an effective anti-inflammatory monomer, improved MI/RI via suppression of inflammation. Left anterior descending (LAD) coronary artery induced ischemia/reperfusion (I/R) of rats or A20 silencing mice, as well as hypoxia/reoxygenation (H/R) induced damages of primary cultured rat neonatal ventricular myocytes or A20 silencing ventricular myocytes, respectively, served as MI/RI model in vivo and in vitro to discuss the anti-I/R injury properties of GB. We found that GB significantly alleviated the symptoms of MI/RI evidently by reducing infarct size, preventing ultrastructural changes of myocardium, depressing Polymorphonuclears (PMNs) infiltration, lessening histopathological damage and suppressing the excessive inflammation. Further study demonstrated that GB remarkably inhibited NF-κB p65 subunit translocation, IκB-α phosphorylation, IKK-ß activity, as well as the downstream inflammatory cytokines and proteins expressions via zinc finger protein A20. In conclusion, GB could alleviate MI/RI-induced inflammatory response through A20-NF-κB signal pathway, which may give us new insights into the preventive strategies for MI/RI disease.