The present paper establishes a three-dimensional solid model of cable tunnel. Considering both the engineering cost and safety, different cross-sectional forms and sizes are proposed firstly. Then the finite element method is used to analyze the strength and deformation of the structure under different embedding depths. Finally, a better cross-sectional shape is chosen under the premise of safety and cost by comparing the results. The results can be used as a reference to the design of actual engineering structures.

ObjectivesTransient perivascular inflammation of the carotid artery (TIPIC) syndrome is a recently recognized clinicoradiological entity that has not yet been formally incorporated into established disease classifications. It is frequently overlooked in clinical practice because of its unclear etiology and nonspecific symptoms. This study aimed to provide a comprehensive summary of the existing literature to improve clinical awareness and diagnostic accuracy.MethodsA retrospective analysis of literature on TIPIC syndrome published before May 2024 was performed, while we reported a case of TIPIC syndrome. The results of both were collated and discussed.ResultsA total of 58 reports including 137 patients with TIPIC were identified. The median age of the patients was 48 years, with a female predominance. All patients presented with neck pain or other concomitant symptoms, mostly with unilateral involvement. All patients had a characteristic imaging presentation with eccentric inflammatory infiltrates in the vessel wall and surrounding tissues. About 1/3 of the patients had luminal stenosis but no blood flow disturbances. The median time to resolution of neck pain symptoms in patients was 2 weeks. Both clinical symptoms and imaging abnormalities may resolve spontaneously or following pharmacological treatment.ConclusionsTIPIC syndrome appears to be a self-limiting condition that may involve transient immune-mediated mechanisms. Clinical awareness of this disease is needed to prevent missed diagnosis or misdiagnosis. The role of imaging in differential diagnosis and follow-up should be appreciated. There are still many unknowns in TIPIC syndrome and a large number of clinical studies are needed to fill these gaps.

Hypertrophic cardiomyopathy (HCM), characterised by abnormal ventricular thickening, involves complex mechanisms including gene mutations, calcium dysregulation, mitochondrial dysfunction, and oxidative stress. Oxidative stress plays a pivotal role in the progression of HCM by mediating cardiomyocyte injury and remodelling. This study systematically analysed HCM transcriptomic data using differential gene expression, weighted gene co-expression network analysis (WGCNA), and unsupervised consensus clustering to identify key genes and classify HCM subtypes. Four oxidative stress-related characteristic genes (DUSP1, CCND1, STAT3, and THBS1) were identified using LASSO regression, SVM-RFE, and Random Forest algorithms. Their functional significance was validated by immune infiltration analysis, drug prediction using the cMAP database, and molecular docking. Single-cell RNA sequencing revealed their cell-type-specific expression, and in vitro experiments confirmed their role in HCM. These findings provide insights into oxidative stress mechanisms and potential therapeutic targets for HCM.

BACKGROUND:Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat/high-sucrose diet (HFHSD)-induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg2+/Mn2+-dependent 1B)-lysine 63(K63) deubiquitination. In this study, we aimed to elucidate the role and mechanisms underlying PPM1B deubiquitination in HFHSD-induced arterial stiffness.METHODS:Enzymes governing PPM1B deubiquitination were identified through small interfering RNA (siRNA) screening and mass spectrometry. Glutathione S-transferase pull-down, coimmunoprecipitation, protein purification, and immunofluorescence were used to explore the mechanism underlying PPM1B deubiquitination. Doppler ultrasound was used to evaluate HFHSD-induced arterial stiffness in mice, and telemetry was used to record pulsatile (systolic and diastolic) blood pressure.RESULTS:Smooth muscle cell-specific PPM1B overexpression attenuated HFHSD-induced arterial stiffness in mice in a PPM1B-K326-K63-linked polyubiquitination-dependent manner. Mechanistically, ABRO1 (Abraxas brother 1; a core BRCC36 [BRCA1/BRCA2 (breast cancer type 1/2)-containing complex subunit 36] isopeptidase complex component) directly bound YAP and underwent liquid-liquid phase separation with YAP and PPM1B in a YAP-dependent manner, which in turn promoted PPM1B deubiquitination. Furthermore, smooth muscle cell-specific Abro1-knockout mice and Brcc3-knockout mice showed attenuated HFHSD-induced arterial stiffness and activation of transforming growth factor-beta-Smad (mothers against decapentaplegic homolog) signaling.CONCLUSIONS:We elucidated the PPM1B deubiquitination mechanisms and highlighted a potential therapeutic target for metabolic syndrome-related arterial stiffness.

ObjectiveThis study aimed to validate the efficiency of Doppler ultrasonography for predicting the innominate, subclavian, and common carotid artery stenosis.MethodsThis retrospective multicenter study between 2013 and 2022 enrolled 636 patients who underwent carotid Doppler ultrasonography and subsequent digital subtraction angiography. And 58 innominate artery stenosis, 147 common carotid artery stenosis, and 154 subclavian artery stenosis were included. The peak systolic velocity at innominate, subclavian, and common carotid artery, and velocity ratios of innominate artery to common carotid artery, innominate artery to subclavian artery, and common carotid artery to internal carotid artery were measured or calculated. The threshold values were determined using receiver operating characteristic analysis.ResultsThe threshold values of innominate artery stenosis were peak systolic velocity >206 cm/s (sensitivity: 82.8%; specificity: 91.4%) to predict ≥50% stenosis and >285 cm/s (sensitivity: 89.2%; specificity: 94.9%) to predict ≥70% stenosis. The threshold values of common carotid artery stenosis were peak systolic velocity >175 cm/s (sensitivity: 78.2%; specificity: 91.9%) to predict ≥50% stenosis and >255 cm/s (sensitivity: 87.1%; specificity: 87.2%) to predict ≥70% stenosis. The threshold values of subclavian artery stenosis were peak systolic velocity >200 cm/s (sensitivity: 68.2%; specificity: 84.4%) to predict ≥50% stenosis and >305 cm/s (sensitivity: 57.9%; specificity: 91.4%) to predict ≥70% stenosis.ConclusionsSymptomatic patients with ultrasonic parameters of velocity at innominate artery ≥206 cm/s, velocity at common carotid artery ≥175 cm/s, or velocity at subclavian artery ≥200 cm/s need to be considered for further verification and whether revascularization is necessary.

Deep vein thrombosis (DVT) is an important complication of stroke. As coronavirus disease 2019 (COVID-19) enters the stage of persistent and long-term management, the clinical management of DVT in stroke patients may require adjustment. The present study evaluated whether there was an increased risk of DVT in stroke patients during the COVID-19 period. Furthermore, we analyzed the possible risk factors and developed an easy-to-use nomogram to predict DVT in stroke patients during the long-term management of COVID-19. A total of 7087 stroke patients during the COVID-19 period and 14,174 patients with age, sex, and National Institutes of Health Stroke Scale (NIHSS) scores matched before the period from four centers were included. The incidence of DVT in stroke patients during the COVID-19 period (20.5%) was significantly higher than that before this period (15.9%, P < .001). Age, body mass index, smoking, D-dimer, physical activity level, NIHSS score, and intermittent pneumatic compression were significant predictors of DVT during the COVID-19 period ( P < .05). A nomogram was constructed; internal and external validations showed high accuracy, and decision curve analysis showed excellent clinical applicability. This nomogram could evaluate the risk of DVT after stroke and assist in its early prevention during the long-term management of COVID-19.

Abstract Objective: Intracranial hypertension is linked to poor prognosis after acute ischemic stroke (AIS). Intracranial pressure can be evaluated by using the ultrasonographic optic nerve sheath diameter (ONSD) and transcranial Doppler (TCD). This study aims to determine whether ONSD and TCD parameters could noninvasively predict the prognosis of AIS patients. Design: Prospective observational blinded study. Setting: Neurology intensive care unit (ICU). Patients: Consecutive patients with AIS. Interventions: ONSD and TCD parameters of 81 AIS patients were obtained upon admission. The Glasgow Outcome Scale scores were evaluated at the 6-month follow-up. The clinical differences between the poor and good prognosis groups were compared. The association between variables and prognosis was assessed, and the cutoff values for the Glasgow Coma Scale (GCS) score and ONSD for predicting poor prognoses were analyzed. Measurements and main results: At the 6-month follow-up, 54 patients had poor prognosis; the ONSDs of the poor and good prognosis groups were 5.45±0.38 and 4.96±0.32, respectively (P<0.001). There were no significant differences in TCD parameters between the two groups. ONSD (odds ratio [OR] 1.4; 95% confidence interval [CI] , 1.2–1.7; P<0.001) and GCS score (OR, 0.7; 95% CI, 0.5–0.9; P=0.003) were independent factors influencing poor prognosis. The best ONSD cutoff value for poor prognosis was 5.21 mm; the sensitivity, specificity, and area under the curve were 87.0%, 82.1%, and 0.862, respectively. Conclusions: Ultrasonographic measurement of ONSD may be a new prognostic indicator of functional outcomes in ICU AIS patients. However, TCD parameters have no significant prognostic value for AIS patients.

Cardiac hypertrophy is the main adaptive response of the heart to chronic loads; however, prolonged or excessive hypertrophy promotes myocardial interstitial fibrosis, systolic dysfunction, and cardiomyocyte death, especially aseptic inflammation mediated by NLRP3 inflammasome, which can aggravate ventricular remodeling and myocardial damage, which is an important mechanism for the progression of heart failure. Various cardiac overloads can cause mitochondrial damage. In recent years, the mitochondria have been demonstrated to be involved in the inflammatory response during the development of cardiac hypertrophy in vitro and in vivo. As the NLRP3 inflammasome and mitochondria are regulators of inflammation and cardiac hypertrophy, we explored the potential functions of the NLRP3 inflammasome and mitochondrial dysfunction in cardiac hypertrophy. In particular, we proposed that the induction of mitochondrial dysfunction in cardiomyocytes may promote NLRP3-dependent inflammation during myocardial hypertrophy. Further in-depth studies could prompt valuable discoveries regarding the underlying molecular mechanisms of cardiac hypertrophy, reveal novel anti-inflammatory therapies for cardiac hypertrophy, and provide more desirable therapeutic outcomes for patients with cardiac hypertrophy.

Objective: Urea transporter-B (UT-B) shows high expression in the heart; However, its role in cardiac hypertrophy remains unknown. This study aimed to investigate the role and mechanism of action of UT-B in cardiac hypertrophy induced by pressure Methods: 16-week-old UT-B knockout and wild-type mice were used in this study. A cardiac hypertrophy model was established by abdominal aorta banding. Echocardiography, histology, hematoxylin and eosin staining, and western blotting were conducted to evaluate cardiac function, morphology, nitric oxide (NO) synthesis, and oxidative stress. Proteasome activities were also examined using a fluorescent peptide substrate. Results: Systolic functional parameters [Ejection fraction (EF), Fractional shortening (FS)] and diastolic functional parameters [ratio of E peak to A peak (E/A)] did not change significantly in UT-B knockout mice compared with those in wild-type mice, but they were decreased significantly after abdominal aorta banding in UT-B knockout mice. Moreover, UT-B knockout mice showed increased heart volume and atrial natriuretic peptide (ANP) expression after abdominal aortic banding. Moreover, reactive oxygen species (ROS) and malondialdehyde levels were upregulated in UT-B knockout mice and were further increased after abdominal aorta banding, whereas the antioxidant enzyme activity was downregulated. In addition, nitric NO levels and endothelial nitric oxide synthase (eNOS) expression were downregulated in UT-B knockout mice and were further decreased after abdominal aorta banding. Conclusions: UT-B knockout enhances cardiac hypertrophy induced by abdominal aorta banding via upregulation of ROS levels and downregulation of NO levels in the heart tissue, suggesting that UT-B plays an important role in the maintenance of cardiac function.

目的:按照教育部和学校"停课不停教、停课不停学"的工作部署,为保障学生在疫情期间的学习病理生理学进行线上教学.方法:线上教学应用网络平台与自建课程相结合的方式,在课程设计上,增加小视频,科技前沿、新冠疫情、思政等元素,在实施过程注重知识传授及价值的引领,在教学完成后对教学效果进行及时检验,最后,通过教学反馈进行教学效果反思.结果:教学改革将现代化信息技术与教学相结合,激发学生的学习兴趣,提高了学生的学习深度,促进了教师教学能力的提升.结论:线上教学是教学改革的一个新尝试,为今后的线上线下混合教学奠定了基础.

Urea transporter B (UT-B, encoded by the SLC14A1 gene) is a membrane channel protein involved in urea transmembrane transport. Compared with normal tissues, UT-B expression is significantly decreased in most tumours, especially melanoma. However, the UT-B role in tumorigenesis and development is still unclear. Herein, we investigated the effects of UT-B overexpression on polyamine metabolism and the urea cycle in murine melanoma B16 cells, to explore the roles of mitochondrial dysfunction and p53 activation in cell growth and polyamines metabolism. UT-B overexpression in B16 cells decreased cell growth, increased apoptosis, and significantly altered metabolic pathways related to the urea cycle, which were characterized by reduced production of urea and polyamines and increased production of nitric oxide. Subsequently, we observed that activation of the p53 pathway may be the main cause of the above phenomena. The p53 inhibitor pifithrin-α partially restored the production of polyamines, but the mitochondrial morphology and function were still impaired. Further treatment of UT-B-overexpressing B16 cells with reactive oxygen species scavenging agent N-acetyl-l-cysteine and coenzyme Q10 restored cell viability and mitochondrial function and increased polyamine production. In conclusion, UT-B overexpression caused mitochondrial dysfunction and increased oxidative stress in B16 cells, and then activated p53 expression, which may be one of the mechanisms leading to the decrease in intracellular polyamines.

Objectives: Stroke patients with high intracranial pressure (ICP) may have poor prognosis. Non-invasive ultrasonic optic nerve sheath diameter (ONSD) could evaluate increased ICP. To investigate whether ONSD is valuable for prognosis of patients with acute ischemic stroke (AIS). Methods: AIS receiving intensive care were recruited with the Glasgow Coma Scale (GCS) score. Patients in group A underwent ultrasonic ONSD to assess ICP voluntarily, whereas group B without ONSD. Patients were followed up at discharge and once a week for 3 months with Glasgow Outcome Scale (GOS) score (four to five scores indicated good prognosis and one to three scores indicated poor prognosis). Results: Forty-nine patients were included. GCS scores did not differ significantly between groups A (26 patients) and B (8 ± 3 vs. 7 ± 3, p < 0.05). In group A, ONSD was 5.01 ± 0.48 mm, which correlated with GCS score (p < 0.05). At discharge, the GOS score was higher in group A than in group B (3.35 ± 1.35 vs. 2.57 ± 1.121, p = 0.034). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 13.0%, p = 0.006). At discharge and after 3 months of follow-up, ONSD at admission was correlated with the GOS score in group A (r = -0.648 [p < 0.05] and -0.731 [p < 0.05], respectively). After 3 months of follow-up, the GOS score was higher in group A than group B (3.00 ± 1.673 vs. 2.04 ± 1.430, p < 0.05). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 21.2%, p = 0.039). The Kaplan-Meier curve showed a higher rate of good prognosis in group A than in group B. ONSD (p < 0.05) was an independent predictor of poor prognosis. Conclusion: Non-invasive ultrasonic ONSD could be useful in improving the prognosis of patients with AIS receiving intensive care.

Although the role of bromodomain-containing protein 4 (BRD4) in ovarian cancer, pancreatic cancer, lymphoma, and many other diseases is well known, its function in cutaneous melanoma is only partially understood. The results of the present study show that the BRD4 inhibitor JQ1 promotes the apoptosis of B16 melanoma cells by altering mitochondrial dynamics, thereby inducing mitochondrial dysfunction and increasing oxidative stress. We found that treatment of B16 cells with different concentrations of JQ1 (125 nmol/L or 250 nmol/L) significantly downregulated the expression of protein subunits involved in mitochondrial respiratory chain complexes I, III, IV, and V, increased reactive oxygen species, induced energy metabolism dysfunction, significantly enhanced apoptosis, and activated the mitochondrial apoptosis pathway. At the same time, JQ1 inhibited the activation of AMP-activated protein kinase, a metabolic energy sensor. In addition, we found that the mRNA and protein levels of mitochondrial dynamin-related protein 1 increased, whereas the levels of mitochondrial fusion protein 1 and optic atrophy protein 1 decreased. Mechanistically, we determined that JQ1 inhibited the expression of c-Myc and altered mitochondrial dynamics, eventually leading to changes in the mitochondrial function, metabolism, and apoptosis of B16 melanoma cells.

We intended to explore the potential molecular mechanisms underlying the cardiac conduction block inducted by urea transporter (UT)-B deletion at the transcriptome level. The heart tissues were harvested from UT-B null mice and age-matched wild-type mice for lncRNA sequencing analysis. Based on the sequencing data, the differentially expressed mRNAs (DEMs) and lncRNAs (DELs) between UT-B knockout and control groups were identified, followed by function analysis and mRNA-lncRNA co-expression analysis. The miRNAs were predicted, and then the competing endogenous RNA (ceRNA) network was constructed. UT-B deletion results in the aberrant expression of 588 lncRNAs and 194 mRNAs. These DEMs were significantly enriched in the inflammation-related pathway. A lncRNA-mRNA co-expression network and a ceRNA network were constructed on the basis of the DEMs and DELs. The complement 7 (C7)-NONMMUT137216.1 co-expression pair had the highest correlation coefficient in the co-expression network. NONMMUT140591.1 had the highest degree in the ceRNA network and was involved in the ceRNA of NONMMUT140591.1-mmu-miR-298-5p-Gata5 (GATA binding protein 5). UT-B deletion may promote cardiac conduction block via inflammatory process. The ceRNA NONMMUT140591.1-mmu-miR-298-5p-Gata5 may be a potential molecular mechanism of UT-B knockout-induced cardiac conduction block.

Urea transporter B(UT-B) is a membrane protein that mediates rapid transport of urea across the membrane and involves in the physiological process of the heart. The UT-B null mice developed myocardial hypertrophy with the increase of age. In order to further clarify its pathogenesis, this study intends to investigate the expression and significance of ATP citrate lyase (Acly), a key enzyme of glucolipid metabolism, in the heart of UT-B null mice.

Polyamines are aliphatic compounds with more than two amino groups that play various important roles in human cells. In cancer, polyamine metabolism dysfunction often occurs, and regulatory mechanisms of polyamine. This review summarizes the existing research on the metabolism and transport of polyamines to study the association of oncogenes and related signaling pathways with polyamines in tumor cells. Drugs that regulate enzymes have been developed for cancer treatment, and in the future, more attention should be paid to treatment strategies that simultaneously modulate polyamine metabolism and carcinogenic signaling pathways. In addition, the polyamine pathway is a potential target for cancer chemoprevention. As an irreversible suicide inhibitor of the ornithine decarboxylase (a vital enzyme of polyamine synthesis), Difluoro-methylornithine had been shown to have the chemoprevention effect on cancer. Therefore, we summarized and analyzed the chemoprophylaxis effect of the difluoromethylornithine in this systematic review.

To investigate the mechanism of urea transporter B (UT-B) gene knockout promoting cardiac hypertrophy induced by abdominal aorta constriction in mice.

Urea transporters (UTs) are membrane proteins in the urea transporter protein A (UT-A) and urea transporter protein B (UT-B) families. UT-B is mainly expressed in endothelial cell membrane of the renal medulla and in other tissues, including the brain, heart, pancreas, colon, bladder, bone marrow, and cochlea. UT-B is responsible for the maintenance of urea concentration, male reproductive function, blood pressure, bone metabolism, and brain astrocyte and cardiac functions. Its deficiency and dysfunction contribute to the pathogenesis of many diseases. Actually, UT-B deficiency increases the sensitivity of bladder epithelial cells to apoptosis triggers in mice and UT-B-null mice develop II-III atrioventricular block and depression. The expression of UT-B in the rumen of cow and sheep may participate in digestive function. However, there is no systemic review to discuss the UT-B functions. Here, we update research approaches to understanding the functions of UT-B.

目的 探讨高尿素对心肌细胞脂质代谢的影响.方法 利用心肌细胞H9C2细胞,建立高尿素模型并分成对照组和模型组.模型组于细胞贴壁24h后加入20mM尿素培养,对照组加入磷酸盐缓冲液(PBS),在培养24、48、72h后,通过蛋白免疫印迹实验检测心肌重构标志蛋白心房利钠尿多肽(ANP)表达水平,油红O染色观察心肌细胞脂肪堆积情况,采用酶联免疫检测仪检测心肌细胞总胆固醇、甘油三酯及高、低密度脂蛋白含量变化.结果 与对照组比较,模型组心肌细胞内ANP表达增高,且随时间呈上升趋势(均P<0.05);在24h,模型组心肌细胞内出现大量脂滴;模型组心肌细胞总胆固醇、甘油三酯及高、低密度脂蛋白含量增高(均P<0.05).结论 高尿素可促进心肌细胞发生脂质代谢紊乱.

目的 探讨人参二醇组皂苷(PDS)对内毒素血症小鼠肾脏保护作用,并揭示其保护作用与炎症因子的释放、尿素通道蛋白A2(UT-A2)和尿素通道蛋白A3(UT-A3)的表达关系.方法 构建C57BL/6小鼠内毒素血症模型,实验分为4组,分别为对照组、LPS组、PDS+LPS组和Dexa+LPS组.麻醉下记录心率和平均动脉压;称取体质量和肾脏质量,并计算系数;肾脏固定和冻存,用于HE和免疫组化检测.结果 与对照组比较,LPS组小鼠心率和平均动脉压下降(P＜0.05),TNF-α、IL-6含量明显升高(P＜0.01),肾脏组织UT-A2和UT-A3蛋白表达水平显著降低且肾脏病理炎症增加和肾间质细胞水肿.与模型组比较,PDS+LPS组和Dexa+LPS组均能恢复心率和平均动脉压(P＜0.05);明显降低TNF-α、IL-6含量(P＜0.05),升高肾脏组织UT-A2和UT-A3蛋白的表达并且减轻肾脏病理炎症和间质细胞水肿.结论 人参二醇组皂苷和地塞米松类似,可降低内毒素血症小鼠促炎因子TNF-α、IL-6含量,升高肾脏组织UT-A2和UT-A3蛋白的表达,改善肾脏病理炎症,减轻肾脏间质细胞水肿状态,从而有效防治保护内毒素血症肾脏损伤.