Comprehensive comparative efficacy and safety of potent P2Y12 inhibitors in patients undergoing coronary intervention: A systematic review and meta-analysis.

Potent P2Y12 receptor antagonists have been used widely for patients undergoing percutaneous coronary intervention with different results. Benefits from different regimens various between trials. Randomized controlled trials (RCTs) have restrictive inclusion and exclusion criteria; thus, they may limit the generalizability of the findings to a broader population. This study was aimed to comprehensively investigate the outcomes of potent P2Y12 inhibitors in patients undergoing PCI, including RCTs and real-world evidence (RWE) studies. Multiple electronic databases were systemically reviewed and searched on compared potent P2Y12 inhibitors with clopidogrel. The primary efficacy end point was composite ischemic cardiovascular event and primary safety endpoint was major bleeding. Overall estimates of proportions and incidence rates with 95 % confidence intervals (CI) were calculated using fixed-effects models. Total 24 studies (140,986 patients) underwent coronary intervention were included in this meta-analysis, including 18 RCTs and 6 large cohort studies with propensity score matching. The potent P2Y12 inhibitors including cangrelor, prasugrel, and ticagrelor, significantly decreased the risk of composite adverse cardiovascular ischemic events (95 % CI 0.89-0.96, p < 0.001), but increased major bleeding (95 % CI 1.15-1.33, p < 0.001) or any bleeding (95 % CI 1.21-1.33, p < 0.001) compared with Clopidogrel. This meta-analysis merges RCTs and RWE studies and comprehensively evidences newer potent P2Y12 inhibitors are significantly more effective than clopidogrel in reduction of composite adverse thrombotic events, but the incidence of major or any bleeding was higher compared with clopidogrel.

Patterns and drivers of avian taxonomic and phylogenetic beta diversity in China vary across geographical backgrounds and dispersal abilities.

Geographical background and dispersal ability may strongly influence assemblage dissimilarity; however, these aspects have generally been overlooked in previous large-scale beta diversity studies. Here, we examined whether the patterns and drivers of taxonomic beta diversity (TBD) and phylogenetic beta diversity (PBD) of breeding birds in China vary across (1) regions on both sides of the Hu Line, which demarcates China's topographical, climatic, economic, and social patterns, and (2) species with different dispersal ability. TBD and PBD were calculated and partitioned into turnover and nestedness components using a moving window approach. Variables representing climate, habitat heterogeneity, and habitat quality were employed to evaluate the effects of environmental filtering. Spatial distance was considered to assess the impact of dispersal limitation. Variance partitioning analysis was applied to assess the relative roles of these variables. In general, the values of TBD and PBD were high in mountainous areas and were largely determined by environmental filtering. However, different dominant environmental filters on either side of the Hu Line led to divergent beta diversity patterns. Specifically, climate-driven species turnover and habitat heterogeneity-related species nestedness dominated the regions east and west of the line, respectively. Additionally, bird species with stronger dispersal ability were more susceptible to environmental filtering, resulting in more homogeneous assemblages. Our results indicated that regions with distinctive geographical backgrounds may present different ecological factors that lead to divergent assemblage dissimilarity patterns, and dispersal ability determines the response of assemblages to these ecological factors. Identifying a single universal explanation for the observed pattern without considering these aspects may lead to simplistic or incomplete conclusions. Consequently, a comprehensive understanding of large-scale beta diversity patterns and effective planning of conservation strategies necessitate the consideration of both geographical background and species dispersal ability.

Spatiotemporal variations and influential factors affecting reproductive dynamics of Pacific saury in the Northwest Pacific during fishing season.

This study examined the spatial and monthly variations in reproductive dynamics of Pacific saury collected in the high sea (40°N-49°N, 149°E-168°E) of the northwestern Pacific during the fishing season of the Taiwanese stick-held dip-net fisheries (July-November) from 2018 to 2019. Generalized additive mixed-effects models (GAMMs) were applied to explore the relationship between the probability of maturing and spawning occurrence (PMOS ) and the explanatory variables (month, body length, sea-surface temperature [SST] as fixed effects, and fishing set as a random effect) for the age 0 and age 1 fish, respectively. In addition, the impact of the geographical difference in growth rates of age 0 fish, quantified as the radius of the otolith annual ring, on the PMOS of age 1 fish was explored in the GAMMs. Results showed that the mean values of the condition factor (CF) varied by months, and higher mean CFs were observed north of 45°N. However, the mean values of the gonado-somatic index did not show a clear spatiotemporal pattern. The spatial distribution of the ovarian maturation states revealed that the spawning ground of Pacific saury during July-November was broader than that previously known and had partly overlapped with the high-sea fishing ground. The best GAMM showed that the predicted PMOS of the age 0 fish were generally low (mean = 19%, standard deviation [SD] = 10%) and tended to increase with increasing body length. In contrast, the predicted PMOS were relatively higher (mean = 37%, SD = 10%) for the age 1 fish and increased with increasing SST and decreasing latitude. Two candidate GAMMs, which are equally supported as the best model (ΔAIC < 2), provide evidence that a higher growth rate of age 0 fish may result in higher reproductive activity in age 1 fish. This is one of few studies focusing on the reproductive dynamics of Pacific saury during the fishing season; current limitations, future directions, and conservation implications were discussed.

Baseline dynamics of Symbiodiniaceae genera and photochemical efficiency in corals from reefs with different thermal histories.

Ocean warming and marine heatwaves induced by climate change are impacting coral reefs globally, leading to coral bleaching and mortality. Yet, coral resistance and resilience to warming are not uniform across reef sites and corals can show inter- and intraspecific variability. To understand changes in coral health and to elucidate mechanisms of coral thermal tolerance, baseline data on the dynamics of coral holobiont performance under non-stressed conditions are needed. We monitored the seasonal dynamics of algal symbionts (family Symbiodiniaceae) hosted by corals from a chronically warmed and thermally variable reef compared to a thermally stable reef in southern Taiwan over 15 months. We assessed the genera and photochemical efficiency of Symbiodiniaceae in three coral species: Acropora nana, Pocillopora acuta, and Porites lutea. Both Durusdinium and Cladocopium were present in all coral species at both reef sites across all seasons, but general trends in their detection (based on qPCR cycle) varied between sites and among species. Photochemical efficiency (i.e., maximum quantum yield; Fv/Fm) was relatively similar between reef sites but differed consistently among species; no clear evidence of seasonal trends in Fv/Fm was found. Quantifying natural Symbiodiniaceae dynamics can help facilitate a more comprehensive interpretation of thermal tolerance response as well as plasticity potential of the coral holobiont.

A network pharmacology-based exploration of the active compounds and potential drug targets of Si-Jun-Zi decoction in the treatment of cutaneous squamous cell carcinoma.

Background: Cutaneous squamous cell carcinoma (cSCC), a kind of skin cancer with high rates of morbidity and mortality, occurs frequently in the clinic. Although early surgical treatment can achieve good results, there is no effective prevention and treatment for the recurrence and metastasis of cSCC. As a useful resource to protect humans from disease, traditional Chinese medicine (TCM) has been adopted by clinicians for thousands of years. Methods: In this study, we collected a Chinese medicine formula and then employed a data mining method to analyze drug combinations of Si-Jun-Zi (SJZ) decoction. Multiple databases were used in this study to predict various ingredients, compounds, and their targets in the decoction. The potential targets of cSCC were also obtained from the database in the same way. In addition, as bioinformatics analysis methods, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used in our research as supplementary means to network pharmacology. Finally, we used ultra-performance liquid chromatography (UPLC) fingerprinting to analyze the effective components of the TCM decoction. Results: We detected 559 active compounds from Ginseng, Largehead Atractylodes, India Bread, and Glycyrrhiza Inflata, and selected 136 molecules under specific conditions. The mechanisms of the TCM formula were illustrated by the network pharmacology, such as compounds-herb network, compounds-target network, disease-target network, and target-target interaction network, as well as characteristics of the TCM. Then, GO analysis and KEGG analysis were performed on the compounds in the network using multiple methods of data mining and bioinformatics, and 10 candidate targets were identified. In addition, the UPLC fingerprinting method was used to analyze the components of SJZ decoction. Conclusions: Network pharmacology was performed to investigate the characteristics and mechanism of SJZ decoction, and a bioinformatics method was used to analyze the relationship between the effective compounds of the SJZ TCM decoction and cSCC-related specific targets and pathways, to find a variety of candidate compounds with multi-target activity.

Palladium-catalyzed carboxylative cyclization of propargylic amines with aryl iodides, CO2 and CO under ambient pressure.

A palladium-catalyzed four-component carboxylative cyclization comprising propargylic amines, aryl iodides, CO2 and CO was developed. By selecting Et3N and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as the base, respectively, both terminal and internal propargylic amines proceeded well facilitated by Pd(PPh3)2Cl2, affording the functionalized 2-oxazolones in moderate yields. This protocol enlarges the product diversity based on CO2 conversion and simultaneously provides a cooperative transformation route for both CO2 and CO.

Combined assessment of tumour cell nest size and desmoplastic reaction as an excellent prognostic predictor in oesophageal squamous cell carcinoma.

AIMS: Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC. METHODS: In all, 265 cases with resected ESCCs diagnosed between January 2018 and August 2019 were retrospectively reviewed. All slides were reviewed for assessing TB, CNS, and DR. The Cellular Dissociation Grading and our Combined CNS and DR (CNS/DR) Grading systems were adopted to re-grade ESCCs. RESULTS: High TB activity, small CNS, and immature DR had a strong association with shorter overall survival (OS) and progression-free survival (PFS) (P < 0.001, respectively) in ESCC. Combined assessment of CNS and DR in a 4-tiered grading system displayed a prognostic excellence for survival (P < 0.001), and outperformed the Cellular Dissociation Grading for both OS (area under the curve [AUC], 0.728 versus 0.644, P = 0.043) and PFS (AUC, 0.763 versus 0.667, P = 0.018) by receiver operator characteristic curves. Also, Combined CNS/DR Grading showed superiority in recognizing a G4 subgroup with the worst outcome in our cohort, to whom the most urgent attention needs to be called. CONCLUSIONS: This is the first study to propose a novel Combined Grading system based on CNS and DR in ESCC, which has been demonstrated to be relatively superior to Cellular Dissociation Grading in predicting prognosis. The findings shed new light on the histopathological grading of ESCC and facilitates identifying biologically aggressive ESCCs.

Metal-Free Hydroxymethylation of Indole Derivatives with Formic Acid as an Alternative Way to Indirect Utilization of CO2.

The selective N-alkylation of indole substrates remains an ongoing research challenge for the relative attenuated nucleophilicity toward nitrogen. Herein, we developed the hydroxymethylation of indole derivatives to afford N-alkylated indole products with formic acid. This metal-free process was promoted by the organic base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) using phenylsilane as the reductant under mild conditions. Besides, this strategy represents an alternative way for indirect utilization of CO2, considering the facile hydrogenation of CO2 to produce HCOOH.

Effects of thermal conditioning on the performance of Pocillopora acuta adult coral colonies and their offspring.

Ocean warming induced by climate change is the greatest threat to the persistence of coral reefs globally. Given the current rate of ocean warming, there may not be sufficient time for natural acclimation or adaptation by corals. This urgency has led to the exploration of active management techniques aimed at enhancing thermal tolerance in corals. Here, we test the capacity for transgenerational acclimation in the reef-building coral Pocillopora acuta as a means of increasing offspring performance in warmer waters. We exposed coral colonies from a reef influenced by intermittent upwelling and constant warm-water effluent from a nuclear power plant to temperatures that matched (26 °C) or exceeded (29.5 °C) season-specific mean temperatures for three reproductive cycles; offspring were allowed to settle and grow at both temperatures. Heated colonies reproduced significantly earlier in the lunar cycle and produced fewer and smaller planulae. Recruitment was lower at the heated recruitment temperature regardless of parent treatment. Recruit survival did not differ based on parent or recruitment temperature. Recruits from heated parents were smaller and had lower maximum quantum yield (Fv/Fm), a measurement of symbiont photochemical performance. We found no direct evidence that thermal conditioning of adult P. acuta corals improves offspring performance in warmer water; however, chronic exposure of parent colonies to warmer temperatures at the source reef site may have limited transgenerational acclimation capacity. The extent to which coral response to this active management approach might vary across species and sites remains unclear and merits further investigation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00338-021-02123-9.

Facile synthesis of α-aminophosphine oxides from diarylphosphine oxides, arynes and formamides.

The straightforward synthesis of α-amino phosphine oxides via three-component reactions involving arynes, formamides and diarylphosphine oxides is disclosed. This method employs the aryne to activate formamide, without an external activating reagent, which is operationally simple under mild conditions with high efficiency. Furthermore, mechanistic perception suggests a cascade sequence including formal [2 + 2] cycloaddition of the aryne with a CO bond, and a 1,4-addition of the H-P(O) compounds to the enamine intermediates.

3D digital image microscope system-assisted vasovasostomy and vasoepididymostomy in rats.

Optimal vision and ergonomics are essential factors contributing to the achievement of good results during microsurgery. The three-dimensional (3D) digital image microscope system with a better 3D depth of field can release strain on the surgeon's neck and back, which can improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using a 3D digital image microscope system (3D-DIM) in rats. A total of 16 adult male rats were randomly divided into two groups of 8 each: the standard operating microscope (SOM) group and the 3D-DIM group. The outcomes measured included the operative time, real-time postoperative mechanical patency, and anastomosis leakage. Furthermore, a user-friendly microscope score was designed to evaluate the ergonomic design and equipment characteristics of the microscope. There were no differences in operative time between the two groups. The real-time postoperative mechanical patency rates were 100.0% for both groups. The percentage of vasoepididymostomy anastomosis leakage was 16.7% in the SOM group and 25.0% in the 3D-DIM group; however, no vasovasostomy anastomosis leakage was found in either group. In terms of the ergonomic design, the 3D-DIM group obtained better scores based on the surgeon's feelings; in terms of the equipment characteristics, the 3D-DIM group had lower scores for clarity and higher scores for flexibility and adaptivity. Based on our randomized prospective study in a rat model, we believe that the 3D-DIM can improve surgeon comfort without compromising outcomes in male infertility reconstructive microsurgery, so the 3D-DIM might be widely used in the future.

Cu(II)-Catalyzed Phosphonocarboxylative Cyclization Reaction of Propargylic Amines and Phosphine Oxide with CO2.

Compounds bearing organophosphorus motifs and 2-oxazolidinone have found numerous applications in pharmaceutical chemistry, homogeneous catalysis, and organic materials. Here, we describe an efficient and selective protocol for straightforward access to a series of 5-((diarylphosphoryl)methyl)oxazolidin-2-ones via the copper-catalyzed difunctionalization of the C≡C bond of propargylic amines with CO2 and phosphine oxide. Notably, copper catalysis is a sustainable and benign catalytic mode. This reaction proceeds under mild reaction conditions, which is operationally simple and scalable with a broad scope, exclusive selectivity, and good functional group compatibility. Mechanistic studies suggest a one-pot tandem cyclization/radical addition sequence, along with the phosphorylation/cyclization scheme.

MET exon 14 skipping mutation, amplification and overexpression in pulmonary sarcomatoid carcinoma: A multi-center study.

BACKGROUND: High frequency of MNNG HOS transforming (MET) exon 14 skipping mutation (MET exon 14Δ) has been reported in pulmonary sarcomatoid carcinomas (PSCs). However, the frequencies differ greatly. Our study aims to investigate the frequency of MET alterations and the correlations among MET exon 14Δ, amplification, and protein overexpression in a large cohort of PSCs. MET exon 14Δ, amplification, and protein overexpression were detected in 124 surgically resected PSCs by using Sanger sequencing, fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) respectively. MET exon 14Δ was identified in 9 (7.3%) of 124 cases, including 6 pleomorphic carcinomas, 2 spindle cell carcinomas and 1 carcinosarcoma. MET amplification and protein overexpression were detected in 6 PSCs (4.8%) and 25 PSCs (20.2%), respectively. MET amplification was significantly associated with overexpression (P < 0.001). However, MET exon 14Δ has no correlation with MET amplification (P = 0.370) and overexpression (P = 0.080). Multivariable analysis demonstrated that pathologic stage (hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.28-6.01; P = 0.010) and MET amplification (HR, 4.71; 95% CI, 1.31-16.98; P = 0.018) were independent prognostic factors for poor median overall survival (mOS). MET alterations including MET exon 14Δ and amplification should be recommended as routine clinical testing in PSCs patients who may benefit from MET inhibitors. MET IHC appears to be an efficient screen tool for MET amplification in PSCs.

Clinicopathological, dermoscopic, and ultrastructural observation of annular secondary syphilis on the penis.

Annular syphilis may range from mildly raised lesions with scaly borders to verrucous plaques. Localized annular syphilis on the genitalia has been rarely reported in HIV-negative cases. This paper reports a case of annular secondary syphilis on the penis. Dermoscopy showed peripheral dotted and short linear vessels and white scaling with a relatively clear central area in an erythematous annular plaque. Histopathology revealed mild hyperkeratosis, parakeratosis, psoriasiform acanthosis, and focal basal vacuolar degeneration with lichenoid, perivascular, and periadnexal infiltrate of lymphohistiocytes and plasma cells in the superficial dermis. Silver stain showed several spirochetes in the lower epidermis and superficial dermis. Electron microscopy revealed a few intercellular and intracytoplasmic spirochetes in the basal epidermis and free spirochetes in the papillary dermis. Rapid plasma reagin and Treponema pallidum particle agglutination assays were positive. The lesions disappeared after intramuscular benzathine penicillin, with no relapse at six-month follow-up.

Prevalence and characteristics of peripheral myopic retinopathy in Guangzhou office workers.

AIM: To determine the prevalence and characteristics of peripheral myopic retinopathy among a sample of Guangzhou office workers. METHODS: A cross-sectional study of Guangzhou Chinese office works in different departments and units of the Guangzhou Power Supply Bureau, China, in 2016. Myopic retinopathy was recorded and analyzed with a scanning laser ophthalmoscope and by slit-lamp microscopy combined with a three-mirror contact lens. RESULTS: In total, 1910 eyes of 955 subjects (508 females and 447 males) aged 21-59y were included; 69.6% of these eyes were myopic. The myopia group had a younger age and worse uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) when compared with hyperopia and emmetropia groups (P<0.001). The axial length (AL) was significantly longer, the spherical equivalent (SE) was more serious, and the optic nerve crescent was significantly larger in subjects with myopia than with hyperopia and emmetropia. Subjects with myopia, and especially high myopia, had the highest frequency of myopic retinal 18 changes (49.4%, P<0.001) [white-without-pressure (43.8%, P<0.001), lattice degeneration (4.5%, P=0.044)] among the three groups. Logistic regression confirmed that any myopia (OR: 3.41, P<0.001) [mild myopia (OR: 1.93, P=0.001), moderate myopia (OR:3.64, P<0.001), and high myopia (OR:10.58, P<0.001)], a greater AL (OR: 1.55, P<0.001) and a much higher SE (OR: 0.77, P<0.001) increased the risk for peripheral retinal changes. CONCLUSION: Myopia-related retinal changes are positively associated with greater AL, higher SE, and myopia.

Aqueous proinflammatory cytokines in acute primary angle-closure eyes.

AIM: To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angle-closure (APAC) and age-related cataracts. METHODS: Twenty eyes of 20 APAC patients and 15 eyes of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique. Clinical data were collected for correlation analysis. RESULTS: Seven of the 20 proinflammatory cytokines included in the magnetic bead panel were detectable in both APAC eyes and cataract eyes: interleukin (IL)-10, IL-12, IL-15, IL-21, IL-6, chemokine (C-C motif) ligand 20, and tumor necrosis factor alpha (TNF-α). IL-27 was only detectable in APAC eyes. Compared with the cataract eyes, the APAC eyes had significantly elevated concentrations of IL-12 (P=0.036), IL-15 (P=0.001), IL-6 (P=0.012), and IL-27 (only detectable in APAC eyes). Age was positively correlated with IL-12 (P=0.022) and IL-6 (P=0.037), and time elapsed between APAC onset and aqueous humor samples collection was positively correlated with IL-15 (P=0.037), IL-27 (P=0.040), and TNF-α (P=0.042). CONCLUSION: Several proinflammatory cytokines including IL-12, IL-15, IL-6 and IL-27, were elevated in the APAC eyes and may be implicated in its pathologic mechanism.

Ex-PRESS implantation versus trabeculectomy in Chinese patients with POAG: fellow eye pilot study.

AIM: To compare the outcomes of Ex-PRESS implantation in one eye versus trabeculectomy with mitomycin C in the fellow eye in Chinese patients with primary open-angle glaucoma (POAG). METHODS: This was a prospective, non-randomized comparative study. Forty-eight eyes of 24 patients with bilateral POAG necessitating surgery were included and underwent Ex-PRESS implantation under the scleral flap in one eye and trabeculectomy in the other eye according to patients' choice. Primary outcome measures included mean intraocular pressure (IOP) and success rate. Secondary outcome measures were aqueous flare, postoperative medication use, visual acuity, and incidence of complications. RESULTS: All 24 patients finished a 1-year follow-up. Both groups maintained significant reductions in IOP after surgery throughout the follow-up period. At any point in time, the IOP of the two groups did not differ significantly. The Kaplan-Meier survival curve analysis showed no significant differences in success between the two groups (P=0.289). The mean number of anti-glaucoma medicines and visual acuity in both groups were not significantly different. Eyes with Ex-PRESS implantation had lower aqueous flare values on days 1 and 3 (both P<0.05). Instances of early postoperative hypotony and choroidal effusion were significantly fewer in frequency after Ex-PRESS implantation under the scleral flap compared with those after trabeculectomy (P<0.001). CONCLUSION: Ex-PRESS is comparable to trabeculectomy in terms of IOP, success rate, number of glaucoma medications used, and visual acuity. However, Ex-PRESS resulted in fewer cases of inflammation and a lower rate of complications.