Search

Ting Duan,1,2,* Xin Yang,3,* Jingyu Kuang,4 Wenjie Sun,3 Jin Li,3 Juan Ge,3 Mohan Zhang,3 Xiaobo Cai,3 Peilin Yu,3 Jun Yang,5 Xinqiang Zhu6 1School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China; 2Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China; 3Department of Toxicology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, People’s Republic of China; 4Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, 410073, People’s Republic of China; 5Department of Nutrition and Toxicology, Hangzhou Normal University School of Public Health, Hangzhou, Zhejiang, 311121, People’s Republic of China; 6Medical Research Center, The Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinqiang Zhu; Jun Yang, Email zhuxq@zju.edu.cn; gastate@zju.edu.cnPurpose: The uncoordinated-51 like kinase 1 (ULK1) is an important serine/threonine protein kinase involved in autophagy, especially for the initiation stage. Previous studies have shown that ULK1 could be used as a prognostic marker in predicting poor progression-free survival and a therapeutic target for hepatocellular carcinoma (HCC) when treated with sorafenib; however, its role during hepatocarcinogenesis remains to be elucidated.Methods: CCK8 and colony formation assay were used to detect cell growth ability. Western blotting was performed to determine expression level of protein. Data from public database were downloaded to analyze expression of ULK1 at mRNA level and predict survival time. RNA-seq was conducted to reveal disturbed gene profile orchestrated by ULK1 depletion. A diethylnitrosamine (DEN)-induced HCC mice model was used to uncover the role of ULK1 in hepatocarcinogenesis.Results: ULK1 was up-regulated in liver cancer tissues and cell lines, and knockdown of ULK1 promoted apoptosis and suppressed proliferation of liver cancer cells. In in vivo experiments, Ulk1 depletion attenuated starvation-induced autophagy in mice liver, reduced diethylnitrosamine (DEN)-induced hepatic tumor number and size, and prevented tumor progression. Further, RNA-seq analysis revealed a close relationship between Ulk1 and immunity with significant changes in gene sets enriched in the interleukin and interferon pathways.Conclusion: ULK1 deficiency prevented hepatocarcinogenesis and inhibited hepatic tumor growth, and might be a molecular target for the prevention and treatment of HCC.Keywords: hepatocellular carcinoma, ULK1, RNA-sequencing, apoptosis, autophagy

Yuan Yang,1,2 Ting Cui,1 Zuoxiao Li,2 Jinglun Li,2 Ting Duan,3 Zhengzhou Yuan,2 Changyi Wang,1 Jincheng Wan,1 Cao Li,4 Shujiang Zhang,2 Ling Li,2 Fayun Hu,1 Bo Wu1 1Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Bo Wu; Fayun Hu, Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel +86-18980602142 ; +86-15902861270, Email dr.bowu@hotmail.com; hufayun2006@163.comObjective: This study examined the functional outcomes and safety of endovascular treatment (EVT) in acute ischemic stroke (AIS) patients owing to large vessel occlusion of the anterior circulation, presented during a late-time window (6– 24 hours after last seen well (LSW)) in a real-world practice.Methods: This was a retrospective analysis from a bi-center prospective cohort. According to the stroke treatment, patients with continuous Alberta Stroke Plan Early Aspect score (ASPECTS) ≥ 6 on non-contrast CT (NCCT) and moderate to good collateral state on CT angiography (CTA) were divided into EVT group and standard medical treatment (SMT) group. The primary outcome was the rate of functional independence (90-day mRS ≤ 2). Safety outcomes were the occurrence of symptomatic intracranial hemorrhage (sICH) and the 90-day mortality.Results: Among the 288 enrolled patients (53.5% male, median age 64 years), there were 167 patients in the EVT group and 121 in the SMT group. After multivariable adjustments for potential confounders, EVT was associated with functional independence (adjusted OR: 3.052; 95% confidence interval (CI): 1.553– 5.997; p = 0.001). In the PSM cohort, 44.2% (42/95) of patients in the EVT group versus 18.9% (18/95) in the SMT group achieved functional independence (OR: 3.39, 95% CI: 1.763– 6.517), and there was a significant difference favoring EVT over the SMT in the overall distribution of mRS (OR: 2.170, 95% CI: 1.302– 3.618) at 90 days. The rate of sICH did not differ between the EVT and SMT groups (10.5% vs 8.4%, p = 0.804) nor did 90-day mortality (18.9% vs 22.1%, p = 0.719). No interaction was found in p-values with statistical significance in subgroup analysis.Conclusion: This real-world experience suggests that EVT for late-presenting stroke patients, based on small core on NCCT and moderate to good collaterals on CTA, is associated with better outcomes than SMT alone, with no increase in sICH and 90-day mortality rates.Keywords: endovascular treatment, late time window, propensity score matching, real-world study

Objective: To assess the association between adenomyosis volume, as a reflection of its severity, and the risk of adverse perinatal outcomes. Methods: This multicenter retrospective cohort study was conducted at a comprehensive tertiary care institution and a tertiary maternal and child healthcare hospital, which are the main types of hospital providing maternal medical care in China. The study included pregnant women without adenomyosis (non‐AD cohort) who delivered between 1 January 2021 and 31 December 2021, and women with pregnancy complicated by adenomyosis (AD cohort) who delivered between 1 January 2020 and 31 December 2022. Adenomyosis was diagnosed and measured using transvaginal or transabdominal ultrasound up to 14 weeks of gestation. The adenomyosis volume (V) was calculated based on the sonographic measurement of three dimensions, using the formula V = (length × width × thickness) × 4/3π. Univariate and multivariate logistic regression analyses were conducted to assess the association between adenomyosis and the risk of pregnancy complications. We also performed a sensitivity analysis among 226 pregnancies complicated by adenomyosis that had volume measurements available and 10 507 pregnancies without adenomyosis, using as a threshold for severe adenomyosis the 3rd quartile of adenomyosis volume. Results: The study group included 10 507 pregnant women in the non‐AD cohort and 321 in the AD cohort. Pregnancies complicated by adenomyosis had an increased risk of preterm birth < 37 weeks of gestation (adjusted odds ratio (aOR), 2.39 (95% CI, 1.65–3.48)), spontaneous preterm birth < 37 weeks of gestation (aOR, 2.57 (95% CI, 1.54–4.28)), placenta previa (aOR, 2.57 (95% CI, 1.41–4.67)), cervical incompetence (aOR, 9.70 (95% CI, 4.00–23.55)) and abnormal fetal presentation (aOR, 2.04 (95% CI, 1.39–3.00)), and there was also a non‐significant trend toward increased risk of pre‐eclampsia (aOR, 1.64 (95% CI, 0.94–2.85)). Sensitivity analysis revealed there was a greater risk in pregnancies with severe (≥ 757.5 cm3) vs mild adenomyosis of preterm birth < 37 weeks of gestation (aOR, 5.50 (95% CI, 2.80–10.82) vs aOR, 1.73 (95% CI, 0.98–3.05)), pre‐eclampsia (aOR, 4.94 (95% CI, 2.11–11.58) vs aOR, 1.03 (95% CI, 0.41–2.58)), placenta previa (aOR, 6.37 (95% CI, 2.39–17.04) vs aOR, 1.58 (95% CI, 0.60–4.19)) and cervical incompetence (aOR, 12.79 (95% CI, 2.87–56.93) vs aOR, 4.97 (95% CI, 1.25–19.77)) compared to pregnancies without adenomyosis. The risk of spontaneous preterm birth < 37 weeks and the risk of abnormal fetal presentation was similar between the two subgroups. Conclusion: Pregnancies complicated by adenomyosis, particularly those with severe adenomyosis, have an increased risk of pregnancy complications, including preterm birth, spontaneous preterm birth, placenta previa, cervical incompetence and abnormal fetal presentation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Tita Alissa Listyowardojo,1 Xiaoling Yan,2,3 Stephen Leyshon,1 Bobbie Ray-Sannerud,1 Xin Yan Yu,4 Kai Zheng,4 Tao Duan2,3 1Life Sciences Program, Group Technology and Research, DNV GL, Hovik, Norway; 2Quality and Safety Department, Shanghai First Maternity and Infant Hospital, 3Tongji University School of Medicine, Shanghai, 4Healthcare Department, Business Assurance, DNV GL, Beijing, China Objective: To assess safety culture at a public maternity hospital in Shanghai, China, using a sequential mixed methods approach. The study was part of a bigger study looking at the application of the mixed methods approach to assess safety culture in health care in different organizations and countries.Methodology: A mixed methods approach was utilized by first distributing the Safety Attitudes Questionnaire measuring six safety culture dimensions and five independent items to all hospital staff (n=1482) working in 18 departments at a single hospital. Afterward, semistructured interviews were conducted using convenience sampling, where 48 hospital staff from nine departments at the same hospital were individually interviewed.Results: The survey received a response rate of 96%. The survey findings show significant differences between the hospital departments in almost all safety culture dimensions and independent items. Similarly, the interview findings revealed that there were different, competing priorities between departments perceived to result in a reduced quality of collaboration and bottlenecks in care delivery. Another major finding was that staff who worked more hours per week would perceive working conditions significantly more negatively. Issues related to working conditions were also the most common concerns discussed in the interviews, especially the issue on high workload. High workload was also reflected in the fact that 91.45% of survey respondents reported that they worked 40 hours or longer per week. Finally, interview findings complemented survey findings, thus providing a more complete and accurate picture of safety culture.Conclusion: Hospital leaders need to prioritize interventions focused on improving the quality of cross-department collaboration and reducing workload. A mixed methods assessment of safety culture provides more meaningful, targeted results, enabling leaders to prioritize and tailor improvement efforts to increase the impact of an intervention. Keywords: semi-structured interview, survey, one child policy, the safety attitudes questionnaire, safety climate

Objective: The perinatal outcomes in second-trimester abdominal circumference (AC) discordant twins are yet to be established. The aim of this study was to ascertain perinatal risks associated with second-trimester AC discordance in monochorionic (MC) twins. Method: We conducted a retrospective study of all MC twin pregnancies over a 7-year period. Intertwin AC discordance at 14–26 gestational weeks was analyzed in relation to Doppler abnormalities, obstetric complications, and perinatal adverse outcomes. Results: A total of 246 MC twin pregnancies were included in the analysis. The smaller twins of second-trimester AC discordant pairs were at increased prevalence of abnormal umbilical artery flow (50% versus 24%, p < .001) and low positive A wave of ductus venous flow (24% versus 9%, p = .002). The second-trimester AC discordant twins were at increased risk of oligohydramnios in smaller twin (OR = 2.44, 95% CI = 1.37–4.32, p < .01), cardiomegaly in larger twin (OR = 2.95, 95% CI = 1.01–8.60, p < .05), birth weight of either twin below the 10th percentile for gestational age (OR = 5.56, 95% CI = 2.67–11.59, p < .001), birth weight discordance > 25% (OR = 9.41, 95% CI = 4.46–19.87, p < .001), IUFD (OR = 3.26, 95% CI = 1.76–6.05, p < .001), and severe neonatal morbidity (OR = 1.83, 95% CI = 1.03–3.26, p < .05). The intact survival rate in discordant and concordant twin pairs was 70% and 89%, respectively (p < .001). Conclusions: Early and increase fetal surveillance of the second-trimester AC discordant twins should be utilized to establish perinatal risks, thus allowing prenatal care to improve. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Approximately 60% of patients with kidney renal clear cell carcinoma (KIRC) die within the first 2-3 years. The prognosis for patients with KIRC and its metastases is poor. Ferroptosis and providing immunity are novel treatment targets for several cancers, including KIRC. Therefore, it is important to identify suitable ferroptosis- and immune-related signatures to predict the prognosis and diagnosis of patients with KIRC. MATERIALS AND METHODS: The corresponding data of patients with KIRC were obtained from the Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were used to screen candidate biomarkers in patients with KIRC. RESULTS: We found that four FI-DEGs (BID, MET, LTB4R, and HMOX1) were independently associated with the overall survival of patients with KIRC. The prognosis and diagnosis model constructed using these four biomarkers could predict the outcome of KIRC, as measured by the receiver operating characteristic analyses. CONCLUSIONS: We identified 4 FI-DEGs that could be used as biomarkers in patients with KIRC. The present study not only contributes to understanding the roles of ferroptosis and immunity in the development of KIRC, but also to the diagnosis and prognosis of KIRC, although it remains to be further studied. [ABSTRACT FROM AUTHOR]

To improve the compressor performances at variable conditions, in this research, we used numerical simulation software to analyze and discuss the effects of three kinks of a wavy blade-end on an axial compressor cascade. One of the wavy blade-ends was a traditional structure with a wavy leading edge and a trailing edge (WBE_P). The other two wavy blades were new structures with a straight trailing edge and a wavy leading edge (WBE_R, WBE_S). The difference between WBE_R and WBE_S was that the blade profile used to form the wavy blade was different. For WBE_R, we obtained the wavy leading edge by rotating the element at different heights, and the trailing edge was the center of a circle. For WBE_S, we obtained the wavy leading edge by using a new element with a different camber angle. Because of the new geometry involving some discussions of a variety of parameters, we further discussed the geometric parameters and structure to guide the design and optimization of the blade. We drew some conclusions at the stable condition (6° incidence). For the first case (WBE_P), when the wavelength of the wavy blade-end was increased to 0.3 times the blade height, the total pressure loss was enhanced. When the wavelength was 0.2 times the blade height, the amplitude was 0.06 times the pitch, the minimum area of blocked range (Ab) and the total pressure loss coefficient ζ could be obtained, and the ζ and Ab were decreased by 5.49%, and 12.72% compared with the baseline. Furthermore, to weaken the influence of changed blade profile on the exit airflow angle, we proposed WBE_P and WBE_R with new structures. We further improved the flow-field characteristics of WBE_P by WBE_R, and the ζ and Ab decreased by 5.84% and 13.79% compared with the baseline. Additionally, the stall point was delayed from 7.5° to 7.7° incidence. Therefore, the wavy blade-end applied in the leading edge had a greater contribution to improving the flow characteristic, and the straight trailing edge was beneficial to maintaining the exit flow angle. WBE_S with a smoother blade surface did not show an advantage compared with WBE_R. WBE_R with a wavy blade-end leading edge and a straight trailing edge showed an advantage in improving the cascade performance, which was suitable for use in the stator from the last stage of a high-load axial compressor. [ABSTRACT FROM AUTHOR]