Evaluation of Retinal Microvascular Features in Patients with Amblyopia Based on Optical Coherence Tomography Angiography: A Systematic Review and Meta-Analysis.

BACKGROUND: The performance of optical coherence tomography angiography (OCTA) in macular microvasculature of patients with amblyopia has been widely studied, but these studies have yielded different and controversial results. OBJECTIVES: The aim of this study is to investigate retinal microvascular features in patients with amblyopia undergoing OCTA. METHODS: PubMed, Embase, and Web of Science were searched for published articles comparing the retinal microvascular features between individuals with amblyopia and controls until April 2022. The mean difference with a 95% confidence interval was used to assess continuous variables. RESULTS: The analysis included 17 studies. The whole vessel density of the superficial capillary plexus (SCPVD) was lower in amblyopic eyes (AE) than in normal eyes (NE) in 3 × 3 mm2 scans, while the perifoveal vessel density of superficial and deep capillary plexus was lower in 6 × 6 mm2 scans. The whole, parafoveal vessel density of deep capillary plexus (DCPVD) and parafoveal SCPVD were lower in both scans. The comparison between AE and fellow eyes (FE) revealed no statistical difference in all quadrants except the parafoveal and perifoveal SCPVD and the foveal DCPVD. Additionally, SCPVD in all quadrants except the fovea and DCPVD in all quadrants except the parafoveal were higher in FE compared to NE. No significant difference was found in the foveal avascular area between AE and NE, AE and FE, or NE and FE. CONCLUSIONS: The retinal vessel density of superficial and deep capillary plexus in AE and FE was lower than in NE, and differences were more likely discovered using 6 × 6 mm2 scans. Consequently, OCTA might be explored as a diagnostic tool to identify and monitor patients with amblyopia.

Effects of argatroban therapy for stroke patients: A meta-analysis.

BACKGROUND: The therapeutic efficacy and safety of argatroban for stroke patients remain controversial. The purpose of this study was to collect all evidence and perform a meta-analysis to comprehensively evaluate the effects of argatroban for stroke patients compared with no-argatroban regimens. METHODS: The databases of PubMed, EMBASE and the Cochrane library were searched from their inception up to December 2020. Categorical outcomes were summarized as odds ratio (OR) and 95% confidence interval (CI); while continuous data were pooled as standardized mean difference (SMD) and 95%CI. RESULTS: A total of 11 studies were enrolled. Overall meta-analysis showed infusion of argatroban significantly improved neurological functions of stroke patients compared with control treatment, showing increased National Institutes of Health Stroke Scale (NIHSS) score change (SMD = 1.02; 95% CI, 0.58-1.46, p < 0.001), modified Barthel Index (SMD = 3.81; 95% CI, 2.72-4.89, p < 0.001) as well as a decreased incidence of early neurological deterioration (OR = 0.48; 95% CI: 0.28-0.84, p = 0.01). Argatroban treatment did not increase the risk of symptomatic intracerebral hemorrhage (p = 0.733), asymptomatic intracranial hemorrhage (p = 0.608), gastrointestinal bleeding (p = 0.601), major systemic hemorrhage (p = 0.582) and mortality (p = 0.797), except minor systemic hemorrhage (OR = 2.40; 95% CI: 1.15-5.02, p = 0.020). Subgroup analyses for NIHSS score change and complications obtained the similar conclusions. CONCLUSION: Argatroban infusion may be an effective and safe therapeutic option to improve functional outcomes of stroke patients.

Plasma Exosomal miRNA-139-3p is a Novel Biomarker of Colorectal Cancer.

Objectives: This study investigated plasma exosomal miRNA-139-3p as a blood-based biomarker for the early diagnosis and metastasis monitoring of colorectal cancer (CRC). Patients and Methods: Exosome-rich fractions were isolated from the plasma of 80 CRC patients, and 23 controls using a kit method. We then used real-time polymerase chain reaction (RT-qPCR) to detect miR-139-3p levels in all subjects to evaluate expression levels and the predictive value of plasma exosomal miR-139-3p in CRC. We also collected clinicopathological data to explore correlations between abnormal miR-139-3p expression and clinicopathological parameters. Results: When compared with healthy controls, exosomal miR-139-3p expression levels in CRC patients were significantly down-regulated. Furthermore, these expression levels were lower in metastatic colorectal cancer (mCRC) and submucosal patients. Receiver operating characteristic (ROC) curve analysis showed that exosomal miR-139-3p levels were differentiated between CRC patients and healthy controls, as well as between non-metastatic and metastatic patients. Conclusion: Our findings show that decreased exosomal miR-139-3p expression levels in CRC patient plasma may act as a novel biomarker for the early diagnosis and metastasis monitoring in CRC.

Urinary circulating DNA profiling in non-small cell lung cancer patients following treatment shows prognostic potential.

BACKGROUND: Disease relapse in non-small cell lung cancer (NSCLC) requires close monitoring for early detection. The aim of the current study examines the use of urinary circulating DNA for patients after first line therapies. METHODS: EGFR positive NSCLC patients in stages I-III were profiled using digital droplet PCR (ddPCR). Urinary circulating DNA was collected prior to treatment and all monitored patients had detectable EGFR mutations. Post treatment urinary DNA measurements were taken at multiple time intervals. Results were matched to disease-free survival. RESULTS: Among the 213 patients recruited, 130 had matched EGFR profiles to corresponding tumor tissues. Concentrations of mutant DNA varied with different patients and mean concentration was 220±237 copies/mL. Measurements taken post-treatment showed a significant number of patients with undetectable EGFR mutations in their urine samples. Other patients registered a significant decline in urinary DNA concentrations. For measurements taken post treatment (6-month), we observed a significant increase of positively identified EGFR mutations in urine samples. In the patient group with higher urinary DNA concentration, 91% of the cohort experienced recurrence. CONCLUSIONS: Our results indicated that urinary DNA measurements can potentially be useful for disease monitoring of minimal residual disease (MRD) in NSCLC. This can complement current serial radiographic imaging to provide early detection for lung cancer relapse.

Bacterial Composition and Diversity in Breast Milk Samples from Mothers Living in Taiwan and Mainland China.

Human breast milk is widely recognized as the best source of nutrients for healthy growth and development of infants; it contains a diverse microbiota. Here, we characterized the diversity of the microbiota in the breast milk of East Asian women and assessed whether delivery mode influenced the microbiota in the milk of healthy breast-feeding mothers. We profiled the microbiota in breast milk samples collected from 133 healthy mothers in Taiwan and in six regions of mainland China (Central, East, North, Northeast, South, and Southwest China) by using 16S rRNA pyrosequencing. Lactation stage (months postpartum when the milk sample was collected) and maternal body mass index did not influence the breast milk microbiota. Bacterial composition at the family level differed significantly among samples from the seven geographical regions. The five most predominant bacterial families were Streptococcaceae (mean relative abundance: 24.4%), Pseudomonadaceae (14.0%), Staphylococcaceae (12.2%), Lactobacillaceae (6.2%), and Oxalobacteraceae (4.8%). The microbial profiles were classified into three clusters, driven by Staphylococcaceae (abundance in Cluster 1: 42.1%), Streptococcaceae (Cluster 2: 48.5%), or Pseudomonadaceae (Cluster 3: 26.5%). Microbial network analysis at the genus level revealed that the abundances of the Gram-positive Staphylococcus, Streptococcus, and Rothia were negatively correlated with those of the Gram-negative Acinetobacter, Bacteroides, Halomonas, Herbaspirillum, and Pseudomonas. Milk from mothers who had undergone Caesarian section (C-section group) had a significantly higher abundance of Lactobacillus (P < 0.05) and a higher number of unique unclassified operational taxonomic units (OTUs) (P < 0.001) than that from mothers who had undergone vaginal delivery (vaginal group). These findings revealed that (i) geographic differences in the microbial profiles were found in breast milk from mothers living in Taiwan and mainland China, (ii) the predominant bacterial families Streptococcaceae, Staphylococcaceae, and Pseudomonadaceae were key components for forming three respective clusters, and (iii) a significantly greater number of unique OTUs was found in the breast milk from mothers who had undergone C-section than from those who had delivered vaginally.

Extreme ultraviolet spectrometer for the Shenguang III laser facility.

An extreme ultraviolet spectrometer has been developed for high-energy density physics experiments at the Shenguang-III (SG-III) laser facility. Alternative use of two different varied-line-spacing gratings covers a wavelength range of 10-260 Å. A newly developed x-ray framing camera with single wide strip line is designed to record time-gated spectra with ~70 ps temporal resolution and 20 lp/mm spatial resolution. The width of the strip line is up to 20 mm, enhancing the capability of the spatial resolving measurements. All components of the x-ray framing camera are roomed in an aluminum air box. The whole spectrometer is mounted on a diagnostic instrument manipulator at the SG-III laser facility for the first time. A new alignment method for the spectrometer based on the superimposition of two laser focal spots is developed. The approaches of the alignment including offline and online two steps are described. A carbon spectrum and an aluminum spectrum have been successfully recorded by the spectrometer using 2400 l/mm and 1200 l/mm gratings, respectively. The experimental spectral lines show that the spectral resolution of the spectrometer is about 0.2 Å and 1 Å for the 2400 l/mm and 1200 l/mm gratings, respectively. A theoretical calculation was carried out to estimate the maximum resolving power of the spectrometer.

ABCB1 hypomethylation is associated with decreased antiplatelet effects of clopidogrel in Chinese ischemic stroke patients.

Current predictive models including the CYP2C19 polymorphism and clinical factors still explain only about 12% of variability of clopidogrel responsiveness. Up until recently, the precise mechanism of clopidogrel resistance remains unclear. P-glycoprotein (P-gp) encoded by ABCB1, a transmembrane calcium-dependent efflux pump for clopidogrel, implicated a role in clopidogrel resistance. In this present study, we investigated the methylation status of ABCB1 gene promoter in relation to ABCB1 mRNA expressions and the antiplatelet effects of clopidogrel. This study was a prospective cohort analysis of eligible stroke patients (n = 183, aged 18-75 years) who received clopidogrel (75 mg/day) for at least 5 days before discharge. A final subcohort of 87 patients with CYP2C19*1/*1 genotype were enrolled in the study population. Patients were grouped in quartiles of maximum platelet aggregation (MPA values (Q1, Q2, Q3 and Q4, MPA(Q1) < 14.1%, MPA(Q4) > 35.4%). The methylation status of the ABCB1 promoter was 1.8 times in the Q1 MPA group (10.1 ± 2.4%) than in the Q4 MPA group (5.5 ± 2.1%) (P < 0.001). ABCB1 methylation correlated inversely with MPA (R = - 0.764, P < 0.001) and mRNA expression (R = - 0.839, P < 0.001). Results of a multivariate linear regression model demonstrated that ABCB1 methylation was independently associated with MPA (ß(coef ficient) = - 4.71, P < 0.001). ABCB1 expression was 0.62 times in the Q1 MPA group (5.3 ± 1.4 per thousand) than in the Q4 MPA (8.5 ± 2.5%o), and the expression of ABCB1 correlated positively with ADP-induced MPA (R = 0.791, P < 0.001). ABCB1 promoter methylation status in whole blood appears to be inversely associated with ABCB1 mRNA expressions and MPA. In conclusions, hypomethylation of ABCB1 promoter is associated with a decreased response to clopidogrel in ischemic stroke patients via increased ABCB1 mRNA expression.

Soft x-ray low-pass filter with a square-pore microchannel plate.

A type of low-pass filter devices for soft x rays is investigated by using a microchannel plate (MCP) of small channels with square cross section. The measured transmission spectra on the Beijing Synchrotron Radiation Facility showed that the MCP has excellent bandpass effects below 1.5 keV by grazing incidence and internal multireflections. Combined with filters, the MCP energy bandwidth can be narrowed to 100 eV. In contrast to bandpass made of planar mirrors, the MCP has a much smaller size and better bandpass effects, and can be easily extended to high energy ranges. For low-resolution spectrometer applications of soft x rays, this method allows the monochromator to be replaced by a simple MCP filter and therefore significantly reduces alignment complexity in experiments.

Pharmacokinetics and tolerability of single and multiple doses of ticagrelor in healthy Chinese subjects: an open-label, sequential, two-cohort, single-centre study.

BACKGROUND AND OBJECTIVES: Ticagrelor (Brilinta™) is an antithrombotic agent that reversibly binds to P2Y(12) receptors and inhibits adenosine diphosphate-induced platelet aggregation. Ticagrelor has undergone evaluation in the phase III PLATO trial, which enrolled 18 624 patients with acute coronary syndromes (ACS) from 43 countries, and 6% of patients were Asian. Subsequently, ticagrelor has now been approved in more than 40 countries for the prevention of atherothrombotic events in adult patients with ACS. Gene polymorphisms in drug-metabolizing enzymes may vary with ethnicity, and can alter drug exposure, potentially impacting drug efficacy and/or tolerability. The objectives of this study were to assess the pharmacokinetic parameters of ticagrelor and its active metabolite AR-C124910XX, and the safety and tolerability of ticagrelor in healthy Chinese subjects, following single and multiple oral doses of ticagrelor. METHODS: This trial was an open-label, sequential, two-cohort, single-centre study investigating 90 mg and 180 mg doses of ticagrelor in healthy Chinese subjects. On day 1, 12 subjects received a single oral dose of ticagrelor 90 mg. Following a 2-day washout period, ticagrelor was administered twice daily (90 mg twice daily) on days 4-9 and as a single dose on day 10. After completion of this phase, additional subjects (n = 14) were recruited into the ticagrelor 180 mg group, and received ticagrelor 180 mg under the same dosing schedule. On days 1 and 10 of both dosing schedules, blood samples for pharmacokinetic analyses were collected for 72 hours. RESULTS: Following single and multiple doses at both dose levels, ticagrelor was rapidly absorbed (median time [t(max)] to reach maximum plasma concentration [C(max)] 2 hours) with a mean elimination half-life (t(1/2;)) of 10.9-14.9 hours. AR-C124910XX was rapidly formed (median t(max) 2.0-3.0 hours; mean t(1/2;) 9.1-11.9 hours). Steady-state concentrations of ticagrelor and AR-C124910XX were rapidly established with both dosing regimens. Both parent and metabolite exhibited linear and predictable pharmacokinetics with single and multiple dosing as mean minimum plasma concentration (C(min)), C(max) and area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) were approximately 2-fold higher with ticagrelor 180 mg (e.g. multiple-dosing, geometric mean [% coefficient of variation]: C(max) 1973 [27] and AUC(∞) 18 035 [46]) versus 90 mg (e.g. multiple dosing: C(max) 915 [32] and AUC(∞) 7168 [35]) dosing regimens. Overall, ticagrelor was generally well tolerated in healthy Chinese subjects. Two subjects discontinued in the ticagrelor 90 mg group due to elevated serum levels of ALT and AST. Mild ticagrelor-associated adverse events were seen: bleeding events (90 mg: epistaxis n = 1; 180 mg: gingival bleeding n = 1) and dyspnoea (180 mg: n = 3). CONCLUSION: In healthy Chinese subjects, ticagrelor and AR-C124910XX pharmacokinetics were linear and predictable. Although ticagrelor and AR-C124910XX exposure at steady state were found to be slightly higher in Chinese subjects, these results were broadly similar to previous data in Caucasian subjects. Overall, ticagrelor was well tolerated in healthy Chinese subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00721448.