Impact of Isolated Coronary Microvascular Disease Diagnosed Using Various Measurement Modalities on Prognosis: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHODS: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59-6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.

Theoretical and Experimental Investigations on High-Precision Micro-Low-Gravity Simulation Technology for Lunar Mobile Vehicle.

With the development of space technology, the functions of lunar vehicles are constantly enriched, and the structure is constantly complicated, which puts forward more stringent requirements for its ground micro-low-gravity simulation test technology. This paper puts forward a high-precision and high-dynamic landing buffer test method based on the principle of magnetic quasi-zero stiffness. Firstly, the micro-low-gravity simulation system for the lunar vehicle was designed. The dynamic model of the system and a position control method based on fuzzy PID parameter tuning were established. Then, the dynamic characteristics of the system were analyzed through joint simulation. At last, a prototype of the lunar vehicle's vertical constant force support system was built, and a micro-low-gravity landing buffer test was carried out. The results show that the simulation results were in good agreement with the test results. The sensitivity of the system was better than 0.1%, and the constant force deviation was 0.1% under landing impact conditions. The new method and idea are put forward to improve the micro-low-gravity simulation technology of lunar vehicles.

DIC/Moiré hybrid method based on regular patterns for deformation measurement.

Digital Image Correlation (DIC) is a superior optical method to measure the surface deformation with a high accuracy. Currently, most researches on DIC are based on random patterns. In this paper, A DIC/Moiré hybrid method using regular patterns is proposed for deformation measurement. In this method, a Moiré fringe technique based on correlation coefficient is developed to provide accurate initial deformation estimation for DIC. Experimental results indicate a higher computational efficiency by the proposed method than the conventional DIC method. It is also found that the calculation accuracy increases using regular patterns. The advantage of obtaining accurate initial estimation by the DIC/Moiré hybrid method may enable potential application in deformation measurements.

Primary Acute Angle-Closure Glaucoma: Three-Dimensional Reconstruction Imaging of Optic Nerve Heard Structure in Based on Optical Coherence Tomography (OCT).

BACKGROUND In glaucoma, the cup to plate ratio enlargement is a recognized pathological phenomenon. At present, the research on optic nerve in China and abroad mainly focuses on 2-dimensional research, and the measurement of 3-dimensional volume data is less well studied. Therefore, the recognition of 3-dimensional morphological changes is conducive to timely clinical intervention to prevent or slow down progressive vision loss. MATERIAL AND METHODS In this paper, optical coherence tomography (OCT) volume imaging technology was used to analyze and compare the morphological changes of primary acute angle-closure glaucoma in three-dimensional morphology, reconstruct the volume data of three-dimensional optic nerve head (ONH), and make morphological measurements. RESULTS The rim width of the glaucoma group was significantly lower than that of the control group, and the average volume and intraocular pressure of the optic cup were significantly increased (P<0.05), while the rim width and intraocular pressure of the other group were not significantly changed (P>0.05). CONCLUSIONS We used three-dimensional reconstruction to identify OCT images between glaucoma patients and the control group with significant differences.

Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors.

A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC50 = 5 nM), and strong antiproliferative activity against HCC827 and Ba/F3 (L858R) cell lines. Kinase profiling against a panel of 365 kinases showed that 6g was highly selective for EGFR. Furthermore, 6g showed desirable properties in assays of liver microsome metabolic stability and cytochromes P450 inhibition and preliminary pharmacokinetic study. The overall attractive profile of 6g made it an interesting compound for further development.

Early diagnostic and prognostic value of myocardial strain derived from cardiovascular magnetic resonance in patients with cardiac amyloidosis.

Background: Cardiac amyloidosis (CA) is one of the causes of heart failure with preserved ejection fraction. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume (ECV) fractions is a preferred method to identify CA. However, the requirement of contrast limits its use in renal deficiency patients. Myocardial strain is a promising method without contrast. We sought to assess the early diagnostic and prognostic value of strain. Methods: This retrospective study enrolled 31 patients with systemic amyloidosis (SA) in Peking University First Hospital from January 2014 to January 2019. The patients were categorized into three groups, including 11 CA patients with left ventricular hypertrophy (CA-LVH group), 9 CA patients without LVH (CA-NLVH group), and 11 patients with extracardiac SA (SA group). Strain analysis was performed with CMR images. A least absolute shrinkage and selection operator (LASSO) was used to generate strain score. The receiver operating characteristic (ROC) curve was used to evaluate the early diagnostic efficacy of strain score and other single strain parameter. The primary endpoint was defined as death from all cause or rehospitalization for heart failure. A Cox proportional hazards model was used to assess the index value on the prognosis. Results: In CA patients, as the left ventricular wall thickens, the global and regional strain decrease significantly. A new strain score (strain score = 0.00893 × mid-septal circumferential peak strain + 0.02285 × apical radial peak strain + 0.1541 × apical circumferential peak strain + 0.33097 × epicardial circumferential average peak strain + 0.42232 × endocardial longitudinal average peak strain) generated using LASSO showed that the area under the ROC curve was 0.909. All the patients with outcome events were in CA groups, four were in CA-LVH group and one in CA-NLVH group. New York Heart Association (NYHA) grade [hazard ratio (HR) =14.29, 95% confidence interval (CI): 2.34-87.34, P<0.01], brain natriuretic peptide (HR =20.05, 95% CI: 2.21-182.36, P=0.008), cardiac injury biomarker (HR =11.59, 95% CI: 1.03-130.36, P=0.047), E/E' (mitral inflow to mitral relaxation velocity ratio) (HR =1.09, 95% CI: 1.00-1.18, P=0.040), end-systolic left ventricular volume (HR =1.04, 95% CI: 1.00-1.18, P=0.039) and LGE volume (HR =1.11, 95% CI: 1.02-1.20, P=0.012) positively correlate with events. Better renal function (HR =0.92, 95% CI: 0.86-0.98, P=0.011) and ejection fraction (HR =0.94, 95% CI: 0.88-0.99, P=0.027) appear to be protective factors. Although with no statistical difference, the strain damage had a tendency to predict poor prognosis, i.e., mid-ventricular circumferential strain with HR of 1.25 (95% CI: 1.0-1.57, P=0.050) and strain score with HR of 1.30 (95% CI: 0.98-1.73, P=0.067). Conclusions: Myocardial strain decreased in CA patients. The integrated magnetic resonance imaging (MRI) strain score can serve as a useful tool to identify early myocardial involvement in amyloidosis. The strain damage had a tendency to predict poor prognosis.

Identification and Optimization of Novel Cathepsin C Inhibitors Derived from EGFR Inhibitors.

In the course of developing the biochemistry to chemistry activity-based protein profiling (BTC-ABPP) method, we herein unexpectedly discovered that the epidermal growth factor receptor irreversible inhibitor WZ4002 also functioned as a low micromolar inhibitor of cathepsin C (CatC), a promising target for the treatment of numerous inflammatory and autoimmune diseases. Building on from this discovery, and following structure-activity relationship investigations guided by computational modeling, a novel series of pyridine scaffold compounds were developed as irreversible CatC inhibitors, further culminated in identifying a highly potent and selective inhibitor 22, which displays good metabolic stability and oral bioavailability. In vivo studies revealed that compound 22 clearly displays the ability to inhibit CatC, consequently leading to efficient inhibition of downstream neutrophil serine proteases in both bone marrow and blood. The overall excellent profile of compound 22 made it an interesting candidate for further preclinical investigation.

Focusing on probe-modified peptides: a quick and effective method for target identification.

A new and efficient method focusing on probe-modified peptides was developed to identify the target protein and modification site of a hit compound or a drug. This method exhibited high click conjugation efficiency and few false-positive results. The modification site further facilitated target validation, biological mechanism study and new indications exploration.