Generation of attosecond electron bunches of tunable duration and density by relativistic vortex lasers in near-critical density plasma.

Attosecond electron bunches have wide application prospects in free-electron laser injection, attosecond X/γ-ray generation, ultrafast physics, etc. Nowadays, there is one notable challenge in the generation of high-quality attosecond electron bunch, i.e., how to enhance the electron bunch density. Using theoretical analysis and three-dimensional particle-in-cell simulations, we discovered that a relativistic vortex laser pulse interacting with near-critical density plasma can not only effectively concentrate the attosecond electron bunches to over critical density, but also control the duration and density of the electron bunches by tuning the intensity and carrier-envelope phase of the drive laser. It is demonstrated that this method can efficiently produce attosecond electron bunches with a density up to 300 times of the original plasma density, peak divergence angle of less than 0.5 ∘, and duration of less than 67 attoseconds. Furthermore, by using near-critical density plasma instead of solid targets, our scheme is potential for the generation of high-repetition-frequency attosecond electron bunches, thus reducing the requirements for experiments, such as the beam alignment or target supporter.

[Risk factors for progression to chronic kidney disease in patients with cardiac valve replacement surgery-associated acute kidney injury].

Objective: To explore the risk factors for progression to chronic kidney disease (CKD) in patients with cardiac valve replacement surgery-associated acute kidney injury (AKI). Methods: A retrospective, nested case-control study was conducted at Fuwai Central China Cardiovascular Hospital. The study subjects were patients who underwent cardiac valve replacement surgery from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min-1·(1.73 m2)-1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint event. The baseline clinical data were compared between the two groups. The measurement data with non-normal distribution was represented as M (Q1,Q3). Logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic (ROC) curve was drawn to evaluate the performance for predicting CKD in cardiac valve replacement surgery-associated AKI patients. Results: A total of 149 cardiac valve replacement surgery-associated AKI patients (86 males and 63 females) were included in the study, aged (59.0±10.2) years. There were 27 patients (18.1%) who progressed to new-onset CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. Compared with non-CKD group, patients in CKD group had older age [66 (58, 70) vs 59 (53, 64) years], lower baseline eGFR [76.3 (65.8, 98.5) vs 92.7 (78.5, 101.6) ml·min-1·(1.73 m2)-1], higher proportion of preoperative hypertension [51.9% (14/27) vs 27.9% (34/122)] and serum creatinine at discharge [136 (101, 165) vs 86 (65, 104) µmol/L], and the differences were statistically significant (all P<0.05). The multivariate logistic regression analysis results revealed that older age (OR=1.063, 95%CI: 1.001-1.129, P=0.047), preoperative hypertension (OR=3.070, 95%CI: 1.105-8.532, P=0.031) and higher serum creatinine at discharge (OR=1.026, 95%CI:1.013-1.038, P<0.001) were risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI. The clinical risk model including age, preoperative hypertension, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting progression to CKD in patients with cardiac valve replacement surgery-associated AKI [the area under the curve (AUC)=0.865, 95%CI: 0.790-0.940, P<0.001]. Conclusion: Older age, preoperative hypertension and higher serum creatinine at discharge are risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI.

Direct acceleration of collimated monoenergetic sub-femtosecond electron bunches driven by a radially polarized laser pulse.

High-quality ultrashort electron beams have diverse applications in a variety of areas, such as 4D electron diffraction and microscopy, relativistic electron mirrors and ultrashort radiation sources. Direct laser acceleration (DLA) mechanism can produce electron beams with a large amount of charge (several to hundreds of nC), but the generated electron beams usually have large divergence and wide energy spread. Here, we propose a novel DLA scheme to generate high-quality ultrashort electron beams by irradiating a radially polarized laser pulse on a nanofiber. Since electrons are continuously squeezed transversely by the inward radial electric field force, the divergence angle gradually decreases as electrons transport stably with the laser pulse. The well-collimated electron bunches are effectively accelerated by the circularly-symmetric longitudinal electric field and the relative energy spread also gradually decreases. It is demonstrated by three-dimensional (3D) simulations that collimated monoenergetic electron bunches with 0.75° center divergence angle and 14% energy spread can be generated. An analytical model of electron acceleration is presented which interprets well by the 3D simulation results.

Impact of biologic disease-modifying antirheumatic drugs on fracture risk in patients with rheumatoid arthritis: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to assess the impact of biologic disease-modifying antirheumatic drugs (bDMARDs) use on the risk of fracture in rheumatoid arthritis (RA) by conducting a pooled analysis of adjusted outcomes from individual studies. MATERIALS AND METHODS: PubMed, Embase, and BioMed Central were searched up to 20th January 2021. Multivariable-adjusted odds ratios (OR) or matched estimates on the impact of bDMARDs on fracture risk were pooled. RESULTS: Nine studies were included. We found no statistically significant difference in the risk of fractures in RA patients using bDMARDs vs. non-users. On sensitivity analysis, we found no change in the significance of the effect size on exclusion of any study. There was no statistically significant difference in fracture risk in studies only on tumor necrosis factor (TNF) inhibitors, as well as those including any bDMARDs. Pooled analysis of only three studies indicated a statistically significant reduction in vertebral fractures in bDMARD users vs. non-users. CONCLUSIONS: Within the ambit of several limitations of our review, there seems to be no impact of bDMARDs on the fracture risk in RA patients. Further studies evaluating the type and duration of bDMARD therapy with meticulous adjustment of confounding factors are required to strengthen current evidence.

Molecular cloning, tissue expression and polymorphism analysis of the Caveolin-3 gene in ducks.

1. Duck meat is considered a delicacy, but choosing the best meat is problematic. Caveolin-3 (CAV-3) is a muscle-specific protein marker in animals. The goal of the current study was to detect the characteristics of CAV-3 gene in ducks. 2. Full-length CAV-3 was acquired from ducks (Anas platyrhynchos) using reverse transcriptase PCR and rapid amplification of cDNA ends. DNAMAN software was used for homology comparisons. Quantitative reverse transcription-PCR, PCR-single-strand conformation polymorphism, and sequencing were used to determine CAV-3 expression and polymorphism of a single nucleotide, respectively. The study examined four types of ducks, including Jinding, Chaohu, Cherry Valley, and Gaoyou ducks. 3. The study acquired 1066 bp of CAV-3 cDNA sequences, including a 456 bp complete open reading frame encoding 151 amino acids. Both coding sequences (CDSs) and translated amino acids exhibited highest homology with Gallus gallus (CDS homology 91.67%, amino acids 94.04%), followed by mammalian species (CDS homology 79.0%, amino acids 78.0%). Single nucleotide polymorphism analysis revealed five mutations in exons (A489G, G501A, A557G, T563A, and A602G), and a C805T mutation in an intron. Among amplified polymorphic loci detected using primer 2, allele frequency was higher for A (489A501G507A563T602A) than B (489G501G507G563T602C) or C (489G501A507G563A602C). The highest occurred in Cherry Valley ducks (0.7587). Using primer 4, the M allele frequency was higher than that of the N allele. CAV-3 was most highly expressed in the heart, followed by skeletal muscles. Additionally, CAV-3 had higher expression in heart and breast muscle of overfed Muscovy ducks than control ducks, but no difference was seen in thigh muscle. 4. CAV-3 in ducks had the highest homology with Gallus gallus CAV-3, and it could be used as a marker for muscle quality in ducks.

Adverse events and management of apatinib in patients with advanced or metastatic cancers: A review.

Apatinib (YN968D1) is a novel and highly selective tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2 (VEGFR-2) and is approved as a third-line and subsequent-line treatment for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in China. Apatinib is also widely studied in other solid tumors. With the increase in clinical research of apatinib, its adverse effects have also received widespread attention. Hence, this article summarizes the pharmacological properties of apatinib and reviews its clinical use in advanced or metastatic cancers. We highlight the common adverse reactions of apatinib in clinical applications and we also clarify the corresponding prevention and intervention measures. Overall, this review will help us better understand the safety and efficacy of apatinib treatment.

LINC00707 promotes cell proliferation and invasion of colorectal cancer via miR-206/FMNL2 axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been verified to participate in the regulation of colorectal cancer (CRC). However, the role of LINC00707 in CRC still remains unknown. Here, we aim to study the role of LINC00707 in CRC. PATIENTS AND METHODS: LINC00707 expression in 97 pairs of CRC tissues and adjacent normal tissues was determined by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00707 overexpression or knockdown in SW620 or HCT116 cells was achieved by lentivirus transfection. The proliferation and cell circle progression of established cells were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Cell invasion and migration abilities were studied by transwell assay. Dual-luciferase assay and Western blot was used to verify the underlying mechanism of LINC00707 in CRC. Nude mice were obtained to identify the in vivo function of LINC00707 in CRC. RESULTS: LINC00707 was significantly over-expressed in CRC tissues and cell lines. Up-regulation of LINC00707 promoted cell proliferation, cell cycle progression, invasion, and migration of SW620 cells. Conversely, down-regulation of LINC00707 reduced cell growth and metastasis of HCT116 cells. MiR-206 was verified as a direct target of LINC00707, and its function was inhibited by LINC00707. FMNL2 was a target for miR-206 in CRC cells. Meanwhile, LINC00707 promoted tumor growth of CRC in vivo. CONCLUSIONS: LINC00707 was up-regulated in CRC tissues and cells, which promoted cell proliferation and metastasis via sponging miR-206 to increase FMNL2 expression. This might provide a novel target for the biological treatment of CRC.

Expression of miR-33 from an SREBP2 intron inhibits the expression of the fatty acid oxidation-regulatory genes CROT and HADHB in chicken liver.

1. Limiting the growth of adipose tissue in chickens is a major issue in the poultry industry. In chickens, de novo synthesis of lipids occurs primarily in the liver. Thus, it is necessary to understand how fatty acid accumulation in the liver is controlled. The miR-33 is an intronic microRNA (miRNA) of the chicken sterol regulatory element binding transcription factor 2 (SREBF2), which is a master switch in activating many genes involved in the uptake and synthesis of cholesterol, triglycerides, fatty acids and phospholipids. 2. In the current study, the genes CROT and HADHB known to encode enzymes critical for fatty acid oxidation were predicted to be potential targets of miR-33 in chickens via the miRNA target prediction programs 'miRanda' and 'TargetScan'. Co-transfection and dual-luciferase reporter assays showed that the expression of luciferase reporter gene linked to the 3'-untranslated region (3'UTR) of the chicken CROT and HADHB mRNA was down-regulated by overexpression of the chicken miR-33 (P < 0.05). This down-regulation was completely abolished when the predicted miR-33 target sites in the CROT and HADHB 3'UTR were mutated. 3. Transfecting miR-33 mimics into the LMH cells led to a decrease in the mRNA expression of CROT and HADHB (P < 0.01), and this transfection had a similar effect on the proteins (P < 0.05). In contrast, the expression of CROT in primary chicken hepatocytes was up-regulated after transfection with the miR-33 inhibitor LNA-anti-miR-33 (P < 0.05). 4. Using quantitative RT-PCR, it was shown that the expression of miR-33 was increased in the chicken liver from day 0 to day 49 of age, whereas the CROT and HADHB mRNA levels decreased during the same period. 5. These findings support the conclusion that miR-33 might play an important role in lipid metabolism in the chicken liver by negatively regulating the expression of the CROT and HADHB genes, which encode enzymes critical for lipid oxidation.

EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway.

BACKGROUND: The goal of this study was to analyze the protective role of ARA290 in early renal allograft injury by using a rat model of renal allograft. METHODS: Lewis rats were divided into 3 groups: sham, University of Wisconsin solution (UW), and ARA290. A rat model of renal allograft was established by anastomosis using a titanium ring pin stapler. The kidneys were removed 24 hours after transplantation to accomplish the following: (1) examine the protective effect of ARA290 on renal morphology and function; (2) investigate the underlying mechanism by determining the binding affinity of nuclear factor-κB (NF-κB) to DNA by using an electrophoretic mobility shift assay; (3) observe the effect of ARA290 on macrophage infiltration using immunohistochemistry; and (4) detect messenger RNA (mRNA) expression of inflammatory mediators by using reverse transcriptase polymerase chain reaction. RESULTS: Serum creatinine and blood urea nitrogen levels in the ARA290 group were significantly lower than those in the UW group. Kidney tissue samples from the UW group exhibited morphologic abnormalities and marked macrophage infiltration compared with those in the sham group. In the ARA290 group, renal morphology was greatly improved with decreased macrophage infiltration. The binding affinity of NF-κB to DNA in the ARA290 group was markedly lower than that in the UW and sham groups. The mRNA expression of NF-κB downstream effectors (monocyte chemotactic protein-1; regulated on activation, normal T cell expressed and secreted; intercellular adhesion molecule-1; and vascular cell adhesion molecular-1) was significantly downregulated in the ARA290 group compared with that in the UW group. CONCLUSIONS: ARA290 protects against early renal allograft injury in rats by reducing macrophage infiltration, improving renal morphology, inhibiting mRNA expression of inflammatory mediators, and weakening the binding affinity of NF-κB to DNA.

Correlation between childhood eczema and specific IgG antibody level.

Eczema, a common pediatric dermatosis with unclear pathogenesis, can seriously affect the life quality of children due to its recurrence and long course. Recent study has found that food specific IgG (sIgG) might be involved in the course of eczema. To analyze the correlation between childhood eczema and sIgG and evaluate the role of avoiding taking intolerance food in the treatment of childhood eczema, this study enrolled 216 children with eczema who were admitted to the Taian Maternal and Child Health Care Hospital, Shandong, China, between August 2014 and October 2015. They were divided into an eczema group (N = 140) and an allergy group (N = 76). Eighty healthy children who were admitted to the Department of Children Healthcare in the same period were selected as a control group. Enzymelinked immuno sorbent assay (ELISA) was used to detect the serum sIgG level. The result showed that the sIgG positive rates of children in the eczema group and allergy group were 91.4% and 93.4%, respectively, and the difference had no statistical significance (P > 0.05). However, the sIgG positive rates of children in the eczema group and allergy group were significantly higher than that in the control group (P less than 0.05). Milk and eggs were the major allergy-causing food for children with sIgG positive rates higher than 70%. The sIgG test results revealed that eggs had the highest allergenicity, followed by milk, tomatoes and soybeans, and pork was not highly sensitive. Therefore, it can be concluded that sIgG positive rate of children with eczema is high, and examination of food sIgG antibody in serum is valuable in the diagnosis and treatment of childhood eczema.

Expression of angiogenic factors and plexiform lesions in the lungs of broiler and layer chickens: A comparison.

Plexiform lesions are characteristic histological changes of pulmonary arteries in human patients with severe pulmonary arterial hypertension (PAH) and are regarded as angiogenic lesions. Meat-type broiler chickens are susceptible to PAH and can develop plexiform lesions spontaneously. Whether the lesion development in broilers is associated with PAH predisposition and lung angiogenic environment remains unclear. Moreover, little is known about the cellular origin of these structures. In this work, plexiform lesions were detected in both layer chickens (a strain known to be resistant to PAH) and broiler chickens aged between 1 and 6 wk with normal pulmonary arterial pressures. Within each of the sampled ages, the lesion density did not differ between strains, with an exception of wk 4 when broiler was higher than layer. In contrast to the trend of age-related decline in layers, lesion densities in broilers demonstrated bi-phasic alterations characterized by a gradual decrease during wk 1 to 3 followed by a sudden increase at wk 4. The mRNA of 6 angiogenic factors in the lung tissue, namely, vascular endothelial growth factor receptor (VEGFR)-2, angiopoietin (Ang)-1, angiopoietin receptor Tie-2, transforming growth factor (TGF)-ß1, hepatocyte growth factor (HGF), and interleukin (IL)-8, were differentially expressed between strains. However, none of them was found to be significantly correlated with the lesion density by strain and age-adjusted partial correlation analysis. An in vivo experiment revealed impaired differentiation of endothelial progenitor cells (EPC) into endothelial cells during the producing of plexiform lesions, as evidenced by increased expression of endothelial CD133, a maker of EPC, but reduced expression of CD31, a marker of mature endothelial cells, in the parent vessels of plexiform lesions compared to normal vessels. Collectively, it appears unlikely that the predisposition to PAH or intrapulmonary angiogenic environment contributes to the lesion development in broilers when compared with layers. It is suggested that the lesion development is associated with increased pulmonary arterial pressure, and that local EPC dysfunction may play a role in the process.

Intraoperative assessment of pulmonary artery pressure using transesophageal echocardiography in patients undergoing cardiac surgery.

We performed a retrospective chart review to investigate a potential relation between pulmonary artery (PA) diameter as measured by intraoperative transesophageal echocardiography and PA pressures measured by PA catheter with the aim of determining whether main PA diameter can aid clinicians in the diagnosis of PA hypertension. A total of 82 adult patients undergoing cardiac surgery were included in our study. Main PA diameter showed a moderate correlation with systolic and diastolic pressures, r = 0.576 (95% confidence interval [CI], 0.407-0.703), P < 0.001, and r = 0.504 (95% CI, 0.319-0.648), P < 0.001, respectively. The authors believe that although a moderate correlation exists between main PA diameter and PA pressure, confounding hemodynamic variables prevent main PA diameter from being an accurate and reliable means of diagnosing PA hypertension.

Model Construction for Biological Age Based on a Cross-Sectional Study of a Healthy Chinese Han population.

OBJECTIVES: Biological age (BA) has been proposed to evaluate the aging status in an objective way instead of chronological age (CA). The purpose of our study is to construct a more precise formula of BA in the cross-sectional study based on a largest-ever sample of our studies. This formula aims at better evaluation of body function and exploring the disciplines of aging in different genders and age stages. METHODS: A total of 1,373 healthy Chinese Han (age range, 19-93 years) were recruited from five cities in China, including 581 males and 792 females. Physical examination, blood routine, blood chemistry, and other lab tests were performed to obtain a total of 74 clinical variables. Then, the principal component analysis (PCA) was used to select variables and estimate BA. The BA formula was further validated in a population with some diseases (n=266), including cardiovascular diseases, type 2 diabetes, kidney diseases, pulmonary diseases, cancer and disorders in nervous system. RESULTS: The BA formula was constructed as follows: BA = 0.358 (pulse pressure) + 0.258 (trail making test) - 11.552 (mitral valve E/A peak) + 26.383 (minimum intima-media thickness) + 31.965 (Cystatin C) + 0.163 (CA) - 3.902. In validation of the formula, BAs of patients were older than those of healthy persons. The BA accelerates faster in the middle-aged population than in the elderly population (>75 years old). CONCLUSION: This BA formula can reflect health condition changes of aging better than CA in a Chinese Han population.

Effect of ALK-inhibitors in the treatment of non-small cell lung cancer: a systematic review and meta-analysis.

OBJECTIVE: Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4 (EML4). NSCLC patients with positive ALK-EML4 gene fusion are highly sensitive to ALK-inhibitors. While the efficacy of the ALK-inhibitors in the treatment of NSCLC has been consistently reported, a limited number of randomized, large-scale clinical trials have been reported. The current study was, therefore, designed to systematically review and appraise current knowledge and conduct a meta-analysis on phase I, II, and III clinical trials in which ALK-inhibitors were used to treat NSCLC. MATERIALS AND METHODS: The PubMed online database was thoroughly searched. A total of 26 articles were included in a qualitative systematic review, and four of them were used to conduct the quantitative meta-analysis. RESULTS: We found that ALK inhibitors significantly improved the overall survival (OS) and progress free survival (PFS) of NSCLC patients, especially of ALK or ROS1 gene fusion-positive cases. ALK inhibitors contributed to better therapeutic outcomes regarding increased one-year and two-year OS, PFS, and ORR (Odds ratio: 4.393, 95% CI: 3.302-5.845, p < 0.001). Visual disturbance was the most common side effect observed in the patients treated with crizotinib, whereas mild gastrointestinal reactions, such as diarrhea and nausea, were most frequent in the patients treated with the 2nd generation of ALK inhibitors. CONCLUSIONS: ALK inhibitors are safe and effective in the treatment of NSCLC patients, especially those with positive ALK-EML4 gene fusion or rearrangement.

Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency.

Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.

Laser-Driven Ion Acceleration from Plasma Micro-Channel Targets.

Efficient energy boost of the laser-accelerated ions is critical for their applications in biomedical and hadron research. Achiev-able energies continue to rise, with currently highest energies, allowing access to medical therapy energy windows. Here, a new regime of simultaneous acceleration of ~100 MeV protons and multi-100 MeV carbon-ions from plasma micro-channel targets is proposed by using a ~1020 W/cm2 modest intensity laser pulse. It is found that two trains of overdense electron bunches are dragged out from the micro-channel and effectively accelerated by the longitudinal electric-field excited in the plasma channel. With the optimized channel size, these "superponderomotive" energetic electrons can be focused on the front surface of the attached plastic substrate. The much intense sheath electric-field is formed on the rear side, leading to up to ~10-fold ionic energy increase compared to the simple planar geometry. The analytical prediction of the optimal channel size and ion maximum energies is derived, which shows good agreement with the particle-in-cell simulations.

Dysbiosis of oral buccal mucosa microbiota in patients with oral lichen planus.

OBJECTIVE: The bacterial community structure of buccal mucosa in patients with oral lichen planus was evaluated and compared with healthy control. SUBJECTS AND METHODS: Buccal scraping samples have been taken on 43 oral lichen planus patients (21 erosive and 22 non-erosive) and 21 mucosal healthy volunteers. The V3 hypervariable 16S rDNA region was amplified and sequenced by high-throughput 454 pyrosequencing. RESULTS: 94.26% of the total buccal bacteria were classified into 15 abundant genera. Eight of these abundant genera could be detected in all cases, namely Streptococcus, Prevotella, Haemophilu, Neisseria, Fusobacterium, Leptotrichia, Veillonella and Actinomyces. Four abundant bacteria showed significantly different prevalence at the genus level: Streptococcus was more abundant (P < 0.01) in healthy control group, while Fusobacterium (P < 0.01), Leptotrichia (P < 0.001) and Lautropia (P < 0.001) showed higher abundance in OLP group. Few differences can be found between erosive and non-erosive OLP. In general, 19 'core' OTUs at three levels were defined to be OLP specific, comparing with healthy control group. CONCLUSIONS: These results suggest that OLP is associated with dysbiosis of the oral microbiome. Further studies should be taken to elucidate the inner relationship between these observed changes and OLP development.