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Bleeding gastrointestinal angiodysplasia may occur in patients with vasculitis and can be challenging to treat. We describe the novel use of bevacizumab therapy to treat bleeding gastrointestinal angiodysplasia and severe anemia in a patient with eosinophilic granulomatosis with angiitis complicated by antiphospholipid antibody syndrome requiring indefinite warfarin therapy. Studies confirmed multiple bleeding jejunal angiodysplasias unamenable to endoscopic intervention, and the patient required ongoing support with iron infusions and blood transfusions to maintain a minimally acceptable hemoglobin. Given the severe anemia, need for continued, indefinite antiplatelet and anticoagulation therapy, and failure of standard treatment approaches, the patient was initiated on systemic bevacizumab therapy, on the basis of prior documented success of bevacizumab to manage gastrointestinal telangiectasias in patients with hereditary hemorrhagic telangiectasia. Bevacizumab was highly effective, with rapid resolution of bleeding, normalization of hemoglobin, liberation from hematologic support and no adverse events, including no thromboembolic events. Vascular endothelial growth factor (VEGF-A) rose paradoxically after initiation of bevacizumab and normalized after its discontinuation. Given these findings, use of systemic bevacizumab to manage bleeding angiodysplasia in patients with acquired vascular disorders merits further study.

Background In a few studies, obesity was associated with better outcomes in patients with cardiogenic shock (CS). Although this phenomenon, the “obesity paradox”, reportedly manifests differently based on sex in other disease entities, it has not yet been investigated in CS patients. Methods and results 1,227 patients with CS from The REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock (RESCUE) registry in Korea were analyzed. The study population was classified into obese and non-obese groups according to Asian-Pacific criteria (BMI >25.0 kg/m2 for obese). Clinical impact of obesity on in-hospital mortality according to sex was analyzed using logistic regression analysis and restricted cubic spline curves. In-hospital mortality rate was significantly lower in obese men than non-obese men (34.2% vs. 24.1%, p=0.004) while the difference was not significant in women (37.3% vs. 35.8%, p=0.884). As a continuous variable, higher BMI showed a protective effect in men conversely, BMI was not associated with clinical outcomes in women. Comparing to normal-weight patients, obesity was associated with a decreased risk of in-hospital death in men (multivariable-adjusted OR 0.63, CI 0.43–0.92, p=0.016), not in women (multivariable-adjusted OR 0.94, 95% CI 0.55–1.61, p=0.828). Interaction P value for the association between BMI and sex was 0.023. Conclusions Obesity paradox exists and apparently occurs in men among CS patients. The differential effect of BMI on in-hospital mortality was observed according to sex. Funding Acknowledgement Type of funding sources: None.

Background Relationship between the level of antiplatelet effect and clinical event appears weak in East Asian patients. In addition prognostic implication of platelet reactivity may differ according to index presentation of disease entity (AMI vs. non-AMI). Methods PTRG-PFT consortium was established to determine the linkage of platelet function with long-term clinical outcome during DAPT (aspirin+clopidogrel) in DES-treated East Asian patients (n=11,714). Platelet reactivity was measured using the VerifyNow P2Y12 assay and its level was divided according to quartile distribution (≤168, 169–220, 221–271, ≥272 P2Y12 reaction unit [PRU]). Primary endpoints were incidences of major adverse cardiac and cerebrovascular events (MACCE) post-PCI. Results Impact of platelet reactivity on MACCE occurrence appeared proportionally increased irrespective of type of disease entity, but their relationship was relatively stronger in the AMI vs. non-AMI group (Figure 1A and B). The cutoff of high-risk platelet reactivity was lower in the AMI group compared with the non-AMI group (225 vs. 245 PRU), and the cutoff of low-risk platelet reactivity (immunity zone) was similar between the groups (175 vs. 170 PRU). In the AMI patients (28.5%), 3rd and 4th quartiles significantly increased MACCE rate (HRadjusted 2.19 and 2.24) (Figure 1C and D). However, 4th quartile only was significantly associated with increased risk of MACCE among the non-AMI patients (71.5%) (HRadjusted 2.19). Conclusion Close associations between platelet reactivity and MACCE occurrence were observed irrespective of type of disease entity. In addition, the targeted antiplatelet level to prevent platelet-centric events appeared similar between the AMI and non-AMI patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Korean Society of Intervention Cardiology

ImportanceDespite being one of the fastest-growing populations in the US, the Asian American population is often misrepresented in and omitted from health research and policy debate. There is a current lack of understanding of how Asian American populations are portrayed in medical school curricula.ObjectiveTo assess how Asian American populations and their subgroups are represented in medical school curricula.Design, Setting, and ParticipantsIn this qualitative study, the content of 632 lectures from all 19 courses of the preclinical curriculum at a single US institution from the academic year 2020 to 2021 was analyzed to identify and characterize unique mentions of race and ethnicity as well as granular ethnicity. Among the 632 lectures, we identified 256 nonrepetitive, unique mentions of race and ethnicity or granular ethnicity. These unique mentions were coded and analyzed for emerging patterns of use.Main Outcomes and MeasuresStudy outcomes included (1) the frequency of specific racial and ethnic categories mentioned in the curriculum, (2) the relative proportion of mentions of race and ethnicity that involved or included Asian American data by courses and context, and (3) key themes representing emerging patterns found from qualitative analysis of curriculum content for mentions of Asian American populations or lack thereof.ResultsAmong the 632 lectures, 256 nonrepetitive mentions of race and ethnicity or granular ethnicity were identified; of these, Asian American populations and/or their subgroups were mentioned in 79 of the instances (30.9%). The most common terms used to denote Asian American populations were Asian, with 36 mentions (45.6%); followed by Japanese, with 10 mentions (12.7%); and Chinese, with 8 mentions (10.1%). Overall, there were 26 mentions (10.2%) of American Indian or Alaska Native populations, 12 mentions (4.7%) of Asian and Pacific Islander or Asian American and Pacific Islander populations, 67 mentions (26.2%) of Asian or Asian American populations, 143 mentions (55.9%) of Black or African American populations, 62 mentions (24.2%) of Hispanic or Latino populations, 4 mentions (1.6%) of Native Hawaiian or Pacific Islander populations, and 154 mentions (60.2%) of White populations. During the analysis of the curriculum for representation of Asian American populations, the following 5 key themes emerged from the data: (1) omission, (2) aggregation, (3) inconsistent categorization, (4) misidentification of granular ethnicity, and (5) association of race and ethnicity with disease.Conclusions and RelevanceThis qualitative study suggests that the curriculum from a single US medical school largely mirrors the inappropriate use of race and ethnicity found in published health literature and clinical guidelines. Solutions with long-term results will require collaboration among diverse groups of interest to adopt inclusive research programs and design. Such solutions could better equip students in combating race-based medicine and could promote community outreach programs built based on trust.

Background: Research participant engagement, which we define as recruitment and retention in clinical trials, is a costly and challenging issue in clinical research. Research teams have leveraged a variety of strategies to increase research participant engagement in clinical trials, although a framework and evidence for effective participant engagement strategies are lacking. We (1) developed a novel conceptual framework for strategies used to recruit and retain participants in clinical trials based on their underlying behavioral principles and (2) categorized empirically tested recruitment and retention strategies in this novel framework. Methods: We conducted a synthetic analysis of interventions tested in studies from two Cochrane reviews on clinical trial recruitment and retention, which included studies from 1986 to 2015. We developed a conceptual framework of behavioral strategies for increasing research participant engagement using deductive and inductive approaches with the studies included in the Cochrane reviews. Reviewed interventions were then categorized using this framework. We examined the results of reviewed interventions and categorized the effects on clinical trial recruitment and retention as significantly positive, null, or significantly negative; summary statistics are presented for the frequency and effects of each behavioral strategy type. Results: We analyzed 141 unique interventions across 96 studies: 91 interventions targeted clinical trial research participant recruitment and 50 targeted retention. Our framework included 14 behavioral strategies to improve research participant engagement grouped into four general approaches: changing attitudes by appealing to social motivators, changing attitudes by targeting individual psychology, reducing barriers and cognitive burdens, and providing incentives. The majority of interventions (54%) aimed to reduce barriers or cognitive burdens, with improving comprehension (27%) as the most common specific strategy identified. For recruitment, the most common behavioral strategies tested were building legitimacy or trust (38%) and framing risks and benefits (32%), while financial or material incentives (32%) and reducing financial, time, and social barriers (32%) were most common for retention interventions. Among interventions tested in randomized controlled trials, 51% had a null effect on research participant engagement, and 30% had a statistically significant positive effect. Discussion: Clinical researchers have tested a wide range of interventions that leverage distinct behavioral strategies to achieve improved research participant recruitment and retention. Common behavioral strategies include building legitimacy or trust between research teams and participants, as well as improving participant comprehension of trial objectives and procedures. The high frequency of null effects among tested interventions suggests challenges in selecting the optimal interventions for increasing research participant engagement, although the proposed behavioral strategy categories can serve as a conceptual framework for developing and testing future interventions.

We evaluated the efficacy of sublingual immunotherapy for children aged 5-17 years with atopic dermatitis who were allergic to house dust mites.This open-label, controlled, randomised trial from June 2015 to February 2018 comprised 60 subjects from a specialist allergy centre in South Korea. Half received sublingual immunotherapy for 12 months and the other half formed the control group. The subjects were evaluated using specialist scores and specific immunoglobulin and skin prick tests.Sublingual immunotherapy significantly decreased the mean Scoring Atopic Dermatitis measurements in the sublingual group from baseline (30.2 ± 10.7) to 3 months (20.7 ± 8.5) and the effects persisted at 12 months (21.5 ± 12.4). However, the control group only showed a significant difference between baseline (30.4 ± 11.9) and 12 months (24.3 ± 10.2). The levels of Dermatophagoides farina-specific immunoglobulin G4 significantly increased in the treatment group from baseline (0.6 ± 0.5) to 12 months (1.0 ± 0.7), with no significant changes in the control group. New sensitisations to two or more allergens between baseline and 12 months were significantly lower in the sublingual group (21.4%) than controls (54.2%).Sublingual immunotherapy improved disease severity and prevented new sensitisations in children with atopic dermatitis who were allergic to dust mites.

the early and med-term follow-up results and technical points of new re-dilated stent in the treatment of pulmonary artery bifurcation opening stenosis, and explore its feasibility and advantages. From March 2019 to October 2020, 10 children [5 males, mean age (7±3) years], mean weight 18.75(13.35,23.05) kg with pulmonary artery bifurcation opening stenosis were treated with new re-dilated stents in the Central China Fuwai Hospital. Including 5 cases of tetralogy of Fallot, 4 cases of pulmonary atresia, 1 case of anomalous origin of coronary artery, all children were given new re-dilated stent implantation. Echocardiography, chest X-ray and electrocardiogram were performed 1 day, 3, 6, 12 months after intervention. Pulmonary artery CTA was performed after 6 or 12 months to evaluate the results, including restenosis, malposition and rupture. A total of 16 stents were implanted in 10 children, 5 cases had simultaneous stenosis of bifurcation openings of pulmonary arteries, and 1 stent was implanted in each of the left and right pulmonary artery openings. The pressure of right ventricular and gradient was significantly decreased immediately after intervention, from preoperative (38-80) mmHg(1 mmHg=0.133 kPa) to postoperative (0-22) mmHg, only one patient's pressure gradient is over 20 mmHg (22 mmHg), and all cases discharged successfully. Stent restenosis, malposition, fracture and other abnormalities were not observed in follow-up. Stents implantation for patients with pulmonary artery bifurcation opening stenosis is very more difficult. A good strategy can ensure that the intervention is safe and effective. It not only avoids the risk of repeated surgery, but also achieves good med-term follow-up results.总结应用新型可再扩张支架治疗肺动脉分叉开口狭窄的技术要点及近中期随访结果，探讨其可行性及优势。收集2019年3月至2020年10月郑州大学华中阜外医院应用新型可再扩张支架治疗肺动脉分叉开口狭窄患儿资料共10例，男5例，女5例，年龄为（7±3）岁，体重

P21-activated kinase 1 (PAK1), a serine/threonine protein kinase which functions downstream of RAC and CDC42 GTPase, is activated by a variety of stimuli, including RAS and other growth signaling factors. The extracellular signal kinase (ERK) and protein kinase B (AKT) signal pathways have been implicated in the pathogenesis of cancers. Whether PAK1 is sensitive to KRAS mutation signals and plays a role through ERK and AKT signaling pathways in NSCLC needs to be studied. The expression of PAK1, ERK and AKT was detected in both lung cancer cell lines and clinical samples. PAK1 RNA interference and specific inhibitor of PAK1(IPA-3) were applied to lung cancer cell lines and mouse xenograft tumors. Cell growth was measured by MTT and colony formation assays. Cell migration and invasion were detected by wound healing and transwell assays. RAS mutation was detected by Taqman probe method. Correlation between KRAS, PAK1, ERK and AKT activities was analyzed in lung cancer patients. PAK1 was highly expressed not only in RAS mutant but also in RAS wild-type lung cancer cells. Using specific inhibitor of PAK1, IPA-3 and PAK1 RNA interference, cell proliferation, migration and invasion of lung cancer cells were reduced significantly, accompanied by decreased activities of ERK and AKT. Dual inhibition of ERK and AKT suppressed these cellular processes to levels comparable to those achieved by reduction in PAK1 expression. In NSCLC patients, PAK1 was not correlated with KRAS mutation but was significantly positively correlated with pERK and pAKT. PAK1 played roles in NSCLC proliferation and invasion via ERK and AKT signaling and suggested a therapeutic target for NSCLC.

Thermal analysis and Fourier transform infrared spectroscopy were used to investigate the thermal stability of two low-dielectric constant (Dk)/dielectric loss (Df) inks based on polyurethane acrylate. According to Arrhenius law, the Flynn–Wall–Ozawa method was used to calculate the apparent activation energy (as the standard apparent activation energy E0) of the ink film at weight loss rates were 10, 50 and 70% for the evaluation of its thermal aging performance. Results show that the activation energy of the ink compounded with acrylic fluorocarbon resin and polyurethane acrylate is relatively high. The Aehar–Brindey–Sharp–Wend–Worth differential method was used to analyze the most probable mechanism function of the ink film layer. The first, second, and third segments of the thermal decomposition temperature of the ink film are speculated to range from 126 to 247°C, from 247 to 384°C (follows the 3d diffusion model, and from 384 to 508°C (third-order chemical reaction), respectively. This article provides theoretical reference for the formulation design of 5G ink from the perspective of thermal decomposition mechanism and thermal stability.

Background and purpose Soluble ST2 (sST2) is a promising biomarker in inflammation, atherosclerosis and cardiovascular diseases. We investigated the association between serum sST2 and poor outcome in patients with transient ischaemic attack (TIA)/ischaemic stroke. Methods Patients within 24 h after onset and with measured serum sST2 were prospectively enrolled in this study. Poor outcome was a combination of a new stroke event (ischaemic or haemorrhagic) and all-cause death within 90 days and 1 year. The associations of serum sST2 with poor outcome were analysed by Cox proportional hazards. Results Among the 430 patients included, the median (interquartile range) sST2 was 17.72 (9.31-28.84) ng/mL. A total of 19 (4.4%) and 38 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Compared with the lowest sST2 tertile, hazard ratios (HRs) [95% confidence intervals (CI)] for the highest tertile were 5.14 (1.43-18.51) for poor outcome within 90 days and 3.00 (1.29-6.97) at 1 year after multivariate adjustments. Adding sST2 to a prediction model significantly improved risk stratification of poor outcome in TIA/ischaemic stroke, as observed by the continuous net reclassification improvement of 60.98% (95% CI, 15.37-106.6%, P = 0.009) and integrated discrimination improvement of 2.63% (95% CI, 0.08-5.18%, P = 0.043) at 90 days and the continuous net reclassification improvement of 41.68% (95% CI, 8.74-74.61%, P = 0.013) at 1 year. Conclusions Increased serum sST2 levels in TIA/ischaemic stroke were associated with increased risks of poor outcome within 90 days and 1 year, suggesting that serum sST2 may be a potential long-term prognostic biomarker for TIA/ischaemic stroke.

Carbapenem-resistant P. aeruginosa (CRPA) is particularly worrisome because of its resistance against multiple antimicrobial agents which reduces treatment options. The efflux pump decreases antibiotic abundance, and biofilm impairs the penetration of antibiotics. The aim of the present study was to evaluate the role and relationship of efflux pump and biofilm formation in CRPA isolates obtained from different clinical samples.A total of 110 different clinical samples were collected from three tertiary medical hospitals. The samples were subjected to isolation and identification by standard operating procedures. Species level were identified using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system. Antibiotic susceptibility testing was done by broth microdilution method. Crystal violet (CV) staining for observing the biofilm forming ability and amplification of efflux pump mexA gene were also performed on clinical CRPA isolates. Three efflux pump MexAB-OprM regulatory genes were analyzed using sequencing methods. The expression of mexA gene both in biofilm and planktonic bacteria was observed by Quantitative real-time PCR (qRT-PCR).The results showed that 110 samples were CRPA and among them 83 (75.5%) were MDR isolates. The CV staining showed 105 (95.5%) isolates as biofilm producers while 78 (74.3%) MDR isolates showed biofilm formation. mexA hyperexpression was detected in 27 (24.5%) CRPA isolates while 26 (96.3%) in biofilm forming isolates and 96.3% (26/27) in MDR P. aeruginosa. Multiple mutations in nalC, nalD, and mexR genes were detected. The distinct difference confirmed that the expression of mexA gene in P. aeruginosa biofilm producer was significantly higher than that of planktonic bacteria in vitro, and the efflux pump inhibitor PAβN significantly inhibited biofilms in CRPA isolated from clinical samples.The biofilm and efflux pumps might be two intertwined processes involved in CRPA isolates. Their synergistic effect magnified the drug resistance characteristics of P. aeruginosa.

PPP2R3A plays a key role in the cardiac pathological and physiological processes, yet little is known about how the protein involved in normal myocardium formation and the protein-protein interaction pathways involved. To address this issue, we investigated the role of PPP2R3A in cardiac myocytes and identify PPP2R3A specific protein interaction partners to accelerate the developmental process of the mechanistic studies.PPP2R3A-silenced primary myocardial cell of neonatal rats and H9c2 cells were established by infecting shRNA lentiviral particles. RT-PCR and Western blot were used to determine the expression of PPP2R3A and silencing efficiency. The cell viability was analyzed by CCK-8 kit, then the cell cycles and apoptosis assays were detected by flow cytometry. Novel protein-protein interactions of PPP2R3A were detected by Yeast Two-Hybrid assays using a high-quality human primary cardiomyocyte cDNA library.PPP2R3A-silencing rat primary cardiomyocytes and H9c2 cells were established successfully, and the expression of PPP2R3A was downregulated significantly as confirmed by RT-PCR and Western blot. PPP2R3A silencing can inhibit the myocardial cell proliferation, arrest the cell cycle in the S phase and promote the cardiomyocytes apoptosis. 19 potential candidates like COL1A2, GIPC1and BCL6 specifically interact with PPP2R3A, and COL1A2 was the highest screening frequency, covering 12.5% of the 24 clones. These partners are highly enriched in signaling pathways associated with a variety of cellular processes.A series of studies have discovered that PPP2R3A was closely associated with heart failure and arrhythmia. Our data further confirmed PPP2R3A plays an important role in the cardiomyocytes and PPP2R3A in the regulation of cardiac events via its interaction partners. Therefore, it is a potential therapeutic target for the disease.

Toxic selenium oxyanions and sulfur species are often jointly present in contaminated waters and soils. This study investigated the effect on kinetics and resulting products for bio-reduction of selenium oxyanions in the presence of biologically produced sulfur resulting from bio-oxidation of sulfide in (bio)gas-desulfurization (bio-S0) and of sulfate. Selenite and selenate (~2 mmol L-1) bio-reduction was studied in batch up to 28 days at 30 oC and pH 7 using lactic acid and a sulfate-reducing sludge, 'Emmtec'. Bio-S0 addition increased the selenite removal rate, but initially slightly decreased selenate reduction rates. Selenite reacted with biologically generated sulfide resulting in selenium-sulfur, which upon further bio-reduction creates a sulfur bio-reduction cycle. Sulfate addition increased the bio-reduction rate for both selenite and sulfate. Bio-S0 or sulfate promoted hexagonal selenium formation, whereas without these, mostly amorphous Se0 resulted. With another inoculum, ‘Eerbeek’, bio-S0 accelerated the selenite reduction rate less than for ‘Emmtec’ because of lower sulfur and higher selenite bio-reduction rates. Bio-S0 addition increased the selenate reduction rate slightly and accelerated hexagonal selenium formation. Hexagonal selenium formation is advantageous because it facilitates separation and recovery and is less mobile and toxic than amorphous Se0. Insights into the interaction between selenium and sulfur bio-reduction are valuable for understanding environmental pathways and considerations regarding remediation and recovery.

OBJECTIVE: To explore the difference in phenotype recognition of PsA patients in two clinical scenarios, physical examination with and without ultrasound assessment. METHODS: PsA patients who visited the rheumatology and clinical immunology department of Peking University First Hospital between January 2010 and October 2020, with complete data of clinical and ultrasound assessment were enrolled. The phenotypes were first identified based on physical examination only, and then combined with enthesitis and dactylitis shown on power doppler and gray-scale ultrasound. The phenotype groupings without and with ultrasound assessment were presented with Wayne diagram. The distributions of different clinical phenotypes were compared by using χ(2) test or Fisher's exact test. The differences of clinical phenotypes with and without ultrasound assessment were compared by using Wilcoxon signed rank test. RESULTS: A total of 227 patients with PsA were enrolled with one or more clinical domains. Physical examination revealed that psoriasis was in 209 (92.1%, 209/227) patients, nail involvement in 98 (43.2%, 98/227) patients, peripheral arthritis in 219 (96.5%, 219/227) patients, axial involvement in 25 (11.0%, 25/227) patients, dactylitis in 80 (35.2%, 80/227) patients, and enthesitis in 18 (7.9%, 18/227) patients. Besides 18 patients with clinical enthesitis, ultrasound scan revealed acute enthesitis in 80 patients, with hypoechogenicity (55 cases), tendon thickening (62 cases), and presence of Doppler signals (48 cases). Similarly, dactylitis on ultrasound was found in 18 patients besides those patients with clinical dactylitis. Compared with the phenotypes recognized based on physical examination only, the additional ultrasound assessment revealed that the most common phenotypes, peripheral arthritis was significantly less frequently recognized (49.8% vs. 27.8%, P < 0.001), however on the other hand, the proportion of the patients with peripheral arthritis and enthesitis was significantly increased (4.4% vs. 18.1%, P < 0.001). The phenotype of peripheral arthritis combined with enthesitis, and dactylitis was also dramatically increased (1.8% vs. 17.6%, P < 0.001). CONCLUSION: Ultrasound is a useful tool to identify enthesitis and dactylitis. With the aid of ultrasound assessment, rheumatologists can better identify the lesions of PsA, accurately identify the phenotypes, and further guide the subsequent treatment.

Toxic selenium oxyanions and sulfur species are often jointly present in contaminated waters and soils. This study investigated the effect on kinetics and resulting products for bio-reduction of selenium oxyanions in the presence of biologically produced sulfur resulting from bio-oxidation of sulfide in (bio)gas-desulfurization (bio-S