Well-Posedness by Perturbations for Variational-Hemivariational Inequalities

We generalize the concept of well-posedness by perturbations for optimization problem to a class of variational-hemivariational inequalities. We establish some metric characterizations of the well-posedness by perturbations for the variational-hemivariational inequality and prove their equivalence between the well-posedness by perturbations for the variational-hemivariational inequality and the well-posedness by perturbations for the corresponding inclusion problem

CT findings of COVID-19 in follow-up: comparison between progression and recovery

PURPOSEWe aimed to retrospectively analyze the imaging changes detected in the follow-up of coronavirus disease 2019 (COVID-19) patients on thin-section computed tomography (CT).METHODSWe included 54 patients diagnosed with COVID-19. The mean interval between the initial and follow-up CT scans was 7.82±3.74 days. Patients were divided into progression and recovery groups according to their outcomes. We evaluated CT images in terms of distribution of lesions and imaging manifestations. The manifestations included ground-glass opacity (GGO), crazy-paving pattern, consolidation, irregular line, and air bronchogram sign.RESULTSCOVID-19 lesions showed mainly subpleural distribution, which was accompanied by bronchovascular bundle distribution in nearly 30% of the patients. The lower lobes of both lungs were the most commonly involved. In the follow-up, the progression group showed more involvement of the upper lobe of the left lung than the recovery group. GGO was the most common sign. As the disease progressed, round GGO decreased and patchy GGO increased. On follow-up CT, consolidation increased in the progression group while decreasing in the recovery group. Air bronchogram sign was more commonly observed at the initial examination (90.9%) than at follow-up (30%) in the recovery group, but there was no significant change in the progression group. Pleural effusion and lymphadenopathy were absent in the initial examination, but pleural effusion was observed in three cases after follow-up.CONCLUSIONAs COVID-19 progressed, round GGOs tended to evolve into patchy GGOs, consolidation increased, and pleural effusion could be occasionally observed. As COVID-19 resolved, the crazy-paving pattern and air bronchogram significantly decreased

Exploring the potential of blended learning to promote retention and achievement in higher education professional study programs

In this paper, we present a blended learning model designed for a university professional study program attended by full-time professional workers, i.e. in-service teachers studying in the field of School Administration. The model integrates four main instructional strategies at the program level: mentoring; participation in an online community of professional learning and practice; collaborative concept-mapping with an object-typed knowledge modeling software, and face-to-face seminars in a work setting. Based on interview and observation data collected during two successive small-scale experimentations of the model, we explored potential factors that could have had an impact on students’ academic retention and achievement. Four types of factors were identified: personal, professional, institutional and pedagogical. We found that pedagogical and professional factors, which are insufficiently considered in theoretical models of student retention, are of primary concern for students who work full-time as professionals. A blended learning model designed at the program level and strongly “situated” in the professional practice of the students is a promising avenue to adjust to their career constraints and aspirations and, thus, promoting their academic retention and achievement

Postoperative adjuvant tyrosine kinase inhibitors combined with anti-PD-1 antibodies improves surgical outcomes for hepatocellular carcinoma with high-risk recurrent factors

BackgroundThe clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies on the surgical outcomes of HCC patients with high-risk recurrent factors (HRRFs).MethodsHCC patients who underwent radical hepatectomy at Tongji Hospital between January 2019 and December 2021 were retrospectively enrolled, and those with HRRFs were divided into PAT group and non-PAT group. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups after propensity score matching (PSM). Prognostic factors associated with RFS and OS were determined by Cox regression analysis, and subgroup analysis was also conducted.ResultsA total of 250 HCC patients were enrolled, and 47 pairs of patients with HRRFs in the PAT and non-PAT groups were matched through PSM. After PSM, the 1- and 2-year RFS rates in the two groups were 82.1% vs. 40.0% (P < 0.001) and 54.2% vs. 25.1% (P = 0.012), respectively. The corresponding 1- and 2-year OS rates were 95.4% vs. 69.8% (P = 0.001) and 84.3% vs. 55.5% (P = 0.014), respectively. Multivariable analyses indicated that PAT was an independent factor related to improving RFS and OS. Subgroup analysis demonstrated that HCC patients with tumor diameter > 5 cm, satellite nodules, or vascular invasion could significantly benefit from PAT in RFS and OS. Common grade 1-3 toxicities, such as pruritus (44.7%), hypertension (42.6%), dermatitis (34.0%), and proteinuria (31.9%) were observed, and no grade 4/5 toxicities or serious adverse events occurred in patients receiving PAT.ConclusionsPAT with TKIs and anti-PD-1 antibodies could improve surgical outcomes for HCC patients with HRRFs

Inhibition of UGT1A1 by natural and synthetic flavonoids

Flavonoids are widely distributed phytochemicals in vegetables, fruits and medicinal plants. Recent studies demonstrate that some natural flavonoids are potent inhibitors of the human UDP-glucuronosyltransferase 1A1 (UGT1A1), a key enzyme in detoxification of endogenous harmful compounds such as bilirubin. In this study, the inhibitory effects of 56 natural and synthetic flavonoids on UGT1A1 were assayed, while the structure–inhibition relationships of flavonoids as UGT1A1 inhibitors were investigated. The results demonstrated that the C-3 and C-7 hydroxyl groups on the flavone skeleton would enhance UGT1A1 inhibition, while flavonoid glycosides displayed weaker inhibitory effects than their corresponding aglycones. Further investigation on inhibition kinetics of two strong flavonoid-type UGT1A1 inhibitors, acacetin and kaempferol, yielded interesting results. Both flavonoids were competitive inhibitors against UGT1A1-mediated NHPN-O-glucuronidation, but were mixed and competitive inhibitors toward UGT1A1-mediated NCHN-O-glucuronidation, respectively. Furthermore, docking simulations showed that the binding areas of NHPN, kaempferol and acacetin on UGT1A1 were highly overlapping, and convergence with the binding area of bilirubin within UGT1A1. In summary, detailed structure-inhibition relationships of flavonoids as UGT1A1 inhibitors were investigated carefully and the findings shed new light on the interactions between flavonoids and UGT1A1, and will contribute considerably to the development of flavonoid-type drugs without strong UGT1A1 inhibition.Peer reviewe

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg

Whole-genome resequencing of wild and domestic sheep identifies genes associated with morphological and agronomic traits

Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals

Steroids in the Treatment of IgA Nephropathy to the Improvement of Renal Survival: A Systematic Review and Meta-Analysis

Studies have shown that steroids can improve kidney survival and decrease the risk of proteinuria in patients with Immunoglobulin A nephropathy, but the overall benefit of steroids in the treatment of Immunoglobulin A nephropathy remains controversial. The aim of this study was to evaluate the benefits and risks of steroids for renal survival in adults with Immunoglobulin A nephropathy.We searched the Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE and EMBASE databases. All eligible studies were measuring at least one of the following outcomes: end-stage renal failure, doubling of serum creatinine and urinary protein excretion. Fifteen relevant trials (n = 1542) that met our inclusion criteria were identified. In a pooled analysis, steroid therapy was associated with statistically significant reduction of the risk in end-stage renal failure (RR: 0.46, 95% CI: 0.27 to 0.79), doubling of serum creatinine (RR = 0.34, 95%CI = 0.15 to 0.77) and reduced urinary protein excretion (MD = −0.47g/day, 95%CI = −0.64 to −0.31).We identified that steroid therapy was associated with a decrease of proteinuria and with a statistically significant reduction of the risk in end-stage renal failure. Moreover, subgroup analysis also suggested that long-term steroid therapy had a higher efficiency than standard and short term therapy