Upadacitinib sustained-release tablets for the treatment of chronic refractory gouty arthritis: a case report and literature review

BackgroundGouty arthritis (GA) is a crystal-related joint disease caused by the deposition of monosodium urate (MSU) crystals, directly associated with hyperuricemia resulting from purine metabolism disorder and/or reduced uric acid excretion. Acute attacks of typical gouty arthritis are generally relieved through the clinical use of NSAIDs, colchicine, or glucocorticoids. However, managing patients with chronic refractory gout poses challenges due to complications such as multiple tophi, gouty nephropathy, diabetes, and gastrointestinal bleeding. While there have been numerous studies on gout in recent years, research specifically regarding chronic refractory gout remains limited. The management of such cases still faces several unresolved issues, including recurrent disease flare-ups and poor patient compliance leading to inadequate drug utilization and increased risk of side effects. In this report, we present a case of successful improvement in chronic refractory gouty arthritis using the biologic agent upadacitinib sustained-release tablets.Case presentationOur case report involves a 53 years-old Asian patient with recurrent gouty arthritis who had a history of over 20 years without regular treatment, presenting with tophi and an increasing number of painful episodes. During hospitalization, various analgesics and anti-inflammatory drugs provided inadequate relief, requiring the use of steroids to alleviate symptoms. However, tapering off steroids proved challenging. We decided to add upadacitinib sustained-release tablets to the treatment regimen, which ultimately improved the patient’s condition. After 6 months of follow-up, the patient has not experienced any further acute pain episodes.ConclusionThis case highlights the potential therapeutic effect of upadacitinib sustained-release tablets during the acute phase of chronic refractory gouty arthritis

Abnormal hubs in global network as neuroimaging biomarker in right temporal lobe epilepsy at rest

While abnormal neuroimaging features have been reported in patients suffering from right temporal lobe epilepsy (rTLE), the value of altered degree centrality (DC) as a diagnostic biomarker for rTLE has yet to be established. As such, the present study was designed to examine DC abnormalities in rTLE patients in order to gauge the diagnostic utility of these neuroimaging features. In total, 68 patients with rTLE and 73 healthy controls (HCs) participated in this study. Imaging data were analyzed using DC and receiver operating characteristic (ROC) methods. Ultimately, rTLE patients were found to exhibit reduced right caudate DC and increased left middle temporal gyrus, superior parietal gyrus, superior frontal gyrus, right precuneus, frontal gyrus Inferior gyrus, middle-superior frontal gyrus, and inferior parietal gyrus DC relative to HC. ROC analyses indicated that DC values in the right caudate nucleus could be used to differentiate between rTLE patients and HCs with a high degree of sensitivity and specificity. Together, these results thus suggest that rTLE is associated with abnormal DC values in the right caudate nucleus, underscoring the relevance of further studies of the underlying pathophysiology of this debilitating condition

Effects of liraglutide on ANP secretion and cardiac dynamics

To observe the effects of liraglutide (analog of glucagon-like peptide 1 (GLP-1)) on atrial natriuretic peptide (ANP) secretion and atrial dynamics, an ex vivo isolated rat atrial perfusion model was used to determine atrial ANP secretion and pulse pressure. DPP-4−/− mice were also established in vivo. ANP levels were determined by radioimmunoassay; GLP-1 content was determined by Elisa. The expression levels of GLP-1 receptor (GLP-1R), PI3K/AKT/mTOR, piezo 1, and cathepsin K were analyzed by Western blot. In the clinical study, patients with acute coronary syndrome (ACS) had low levels of plasma GLP-1 but relatively high levels of plasma ANP. In ex vivo (3.2 nmol/L) and in vivo (30 μg/kg) models, liraglutide significantly decreased ANP levels and atrial pulse pressure. Exendin9–39 alone (GLP-1R antagonist) reversibly significantly increased ANP secretion, and the reduction effect of liraglutide on the secret ion of ANP was significantly alleviated by Exendin9–39. Exendin9–39 demonstrated slightly decreased atrial pulse pressure; however, combined liraglutide and Exendin9–39 significantly decreased atrial pulse pressure. Ly294002 (PI3K/AKT inhibitor) inhibited the increase of ANP secretion by liraglutide for a short time, while Ly294002 didn't counteract the decrease in pulse pressure by liraglutide in atrial dynamics studies. Liraglutide increased the expression of GLP-1R and PI3K/AKT/mTOR in isolated rat atria and the hearts of mice in vivo, whereas Exendin9–39 reversibly reduced the expression of GLP-1R and PI3K/AKT/mTOR. Piezo 1 was significantly decreased in wild type and DPP-4−/− mouse heart or isolated rat atria after being treated with liraglutide. Cathepsin K expression was only decreased in in vivo model hearts. Liraglutide can inhibit ANP secretion while decreasing atrial pulse pressure mediated by GLP-1R. Liraglutide probably plays a role in the reduction of ANP secretion via the PI3K/AKT/mTOR signaling pathway. Piezo 1 and cathepsin K may be involved in the liraglutide mechanism of reduction

Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cells by suppression of anti-oxidative and growth factor gene expression

<p>Abstract</p> <p>Background</p> <p>Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria with proved role in pathogenesis of sepsis. Brain injury was observed with both patients dead from sepsis and animal septic models. However, <it>in vitro </it>administration of LPS has not shown obvious cell damage to astrocytes and other relative cell lines while it does cause endothelial cell death <it>in vitro</it>. These observations make it difficult to understand the role of LPS in brain parenchymal injury.</p> <p>Results</p> <p>To test the hypothesis that LPS may cause biological changes in astrocytes and make the cells to become vulnerable to reactive oxygen species, a recently developed highly sensitive and highly specific system for large-scale gene expression profiling was used to examine the gene expression profile of a group of 1,135 selected genes in a cell line, T98G, a derivative of human glioblastoma of astrocytic origin. By pre-treating T98G cells with different dose of LPS, it was found that LPS treatment caused a broad alteration in gene expression profile, but did not cause obvious cell death. However, after short exposure to H₂O₂, cell death was dramatically increased in the LPS pretreated samples. Interestingly, cell death was highly correlated with down-regulated expression of antioxidant genes such as cytochrome b561, glutathione s-transferase a4 and protein kinase C-epsilon. On the other hand, expression of genes encoding growth factors was significantly suppressed. These changes indicate that LPS treatment may suppress the anti-oxidative machinery, decrease the viability of the T98G cells and make the cells more sensitive to H₂O₂stress.</p> <p>Conclusion</p> <p>These results provide very meaningful clue for further exploring and understanding the mechanism underlying astrocyte injury in sepsis <it>in vivo</it>, and insight for why LPS could cause astrocyte injury <it>in vivo</it>, but not <it>in vitro</it>. It will also shed light on the therapeutic strategy of sepsis.</p

한국 드라마 재연(再演)광고가 중국 수용자들에게 미치는 광고효과에 관한 연구

학위논문(석사)--서울대학교 대학원 :언론정보학과,2004.Maste

Study on the Evolution Law of Internal Force and Deformation and Optimized Calculation Method for Internal Force of Cantilever Anti-Slide Pile under Trapezoidal Thrust Load

The evolution law of internal force and deformation of an anti-slide pile affects the slope stability and prevention design in a significant way. Based on the similarity theory, a test system for the bearing characteristics of a cantilever anti-slide pile was constructed, and the physical model test for the bearing characteristics of a cantilever anti-slide pile under trapezoidal thrust load was carried out. The distribution laws of internal force and deformation of a cantilever anti-slide pile were revealed, and the optimized calculation method for internal force of a cantilever anti-slide pile was proposed by taking the elastoplastic characteristics of steel bars and concrete into consideration. Furthermore, a numerical model was employed to conduct a parametric analysis of a cantilever anti-slide pile. The results show that the whole process of stress and deformation of a cantilever anti-slide pile can be classified as the uncracked stage, the cracks emerging and developing stage, and the steel bars yielding&ndash;failing stage. In the uncracked stage, the bending moment of the cantilever anti-slide pile calculated by the traditional method is smaller than that calculated by the optimized calculation method established in this paper. The traditional calculation method is no longer applicable in the stage of cracks emerging and developing. The lateral displacement and bending moment of the cantilever anti-slide pile are negatively and positively correlated with the strength of the pile material, respectively, and the influence of the deterioration of steel bars&rsquo; strength on the ultimate bearing performance of the anti-slide pile is more obvious than that of the deterioration of concrete strength. The bearing capacity of the anti-slide pile could not be significantly improved by increasing the length of the anchored section when the strength of the rock stratum embedded in anchored section was large enough. As the thrust load behind the pile increased, the difference of the bearing performances of the cantilever anti-slide pile under the uniform load and trapezoidal load increased gradually. The research results can provide guidance for the evaluation of the service performance of the cantilever anti-slide pile and the slope stability

Dynamic Response of Seismic Dangerous Rock Based on PFC and Dynamics

Rock slope instability by earthquakes results in substantial economic and property losses. The calculation method of interlayer load and stability coefficient of horizontal complex layered rock slopes in high-intensity areas is established from material mechanics, fracture mechanics, and dynamics. The stability of horizontal layered dangerous rock is calculated after combining it with PFC simulation technology to verify the rationality of the calculation in the Wenchuan area of Sichuan Province. The dynamic response characteristics of dangerous rocks under different weathering degrees are also analyzed. The results show that both methods have an excellent early warning effect on earthquake dangerous rocks. Among the PGA amplification factors, Model 1 has a relatively uniform distribution, Model 2 has a zigzag distribution, Models 3 and 4 have a “U”-shaped distribution, and the most severe acceleration dynamic responses are 4-1 and 4-2 rock blocks. The dynamic acceleration response of mudstone is affected by the crack propagation process of the upper sandstone and exhibits a particular elevation amplification effect. The peak stress gradually decreases with the increase in weathering and elevation. The stress change of the inner chain No. 2 in the horizontal x and y directions is severe, and the stress response of the outer chain No. 1 in the vertical z-direction is severe. It recommends that earthquake disaster protection projects should pay attention to the impact of low-frequency (0–10 Hz) and high-frequency (250 Hz) earthquakes on slope stability