ObjectiveTo investigate the role and underlying mechanism of the Wnt/β-catenin signaling pathway in the process of Xiaojinwan （XJW）-containing serum interfering with endothelial-mesenchymal transition （EMT） in human breast cancer MDA-MB-231 cells. MethodsXJW-containing serum was prepared by intragastric administration of XJW （4 g·kg^-1） to SD rats. MDA-MB-231 cells were cultured in vitro. β-Catenin overexpression and knockdown plasmids were constructed and transfected into MDA-MB-231 cells. The optimal XJW-containing serum （4 g·kg^-1） according to previous studies was used for β-catenin intervention and overexpression experiments. The groups for intervention/overexpression experiments included intervention/overexpression blank group， β-catenin intervention/overexpression group， intervention/overexpression blank + XJW group， and β-catenin intervention/overexpression + XJW group. Cell morphology was observed under a microscope. Flow cytometry was used to detect and record apoptosis rates. Western blot was performed to measure apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and active-Caspase-3］ and EMT-related proteins （E-cadherin， N-cadherin， and vimentin）. Real-time polymerase chain reaction （Real-time PCR） was used to detect β-catenin mRNA expression levels in different groups. ResultsIntervention experiment results showed that compared with the intervention blank group， the β-catenin intervention group and the intervention blank + XJW group showed increased apoptosis rates （P<0.05， P<0.01）， elevated protein levels of Bax， active Caspase-3， and E-cadherin （P<0.05， P<0.01）， and decreased protein levels of Bcl-2 and Vimentin （P<0.05， P<0.01）. β-catenin mRNA expression was reduced in the β-catenin intervention group （P<0.05， 0.63 ± 0.15） and the intervention blank + XJW group （P<0.05， 0.79 ± 0.33）. Compared with the β-catenin intervention group， the β-catenin intervention + XJW group exhibited an increased apoptosis rate （P<0.01）， elevated Bax and active Caspase-3 protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and Vimentin protein levels （P<0.05）. β-catenin mRNA expression was further reduced in the β-catenin intervention + XJW group （P<0.01， 0.22 ± 0.08）. Compared with the intervention blank + XJW group， the β-catenin intervention + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax， active Caspase-3， and E-cadherin protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and vimentin protein levels （P<0.05， P<0.01）. β-catenin mRNA expression was also reduced （P<0.05）. Overexpression experiment results showed that compared with the overexpression blank group， the β-catenin overexpression group exhibited a reduced apoptosis rate （P<0.01）， while the overexpression blank + XJW group showed an increased apoptosis rate （P<0.05）. In the β-catenin overexpression and β-catenin overexpression + XJW groups， Bax and E-cadherin protein levels decreased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels increased （P<0.05）. In the overexpression blank + XJW group， Bax and E-cadherin levels increased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels decreased （P<0.05， P<0.01）. β-catenin mRNA expression increased in the β-catenin overexpression group （P<0.01， 7.26 ± 1.03） but decreased in the overexpression blank + XJW group （P<0.05， 0.73 ± 0.14）. Compared with the β-catenin overexpression group， the β-catenin overexpression + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax and E-cadherin levels （P<0.05）， and decreased N-cadherin and vimentin levels （P<0.05）. β-catenin mRNA expression was reduced （P<0.05， 4.65 ± 1.02）. Compared with the overexpression blank + XJW group， the β-catenin overexpression + XJW group exhibited a reduced apoptosis rate （P<0.01）， decreased Bax and E-cadherin levels （P<0.01）， and increased Bcl-2， N-cadherin， and Vimentin levels （P<0.05）. β-catenin mRNA expression increased （P<0.01）. ConclusionXJW-containing serum inhibits breast cancer cell proliferation by suppressing EMT， which is associated with the regulation of the Wnt/β-catenin pathway.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective:To investigate the application value of cardiac magnetic resonance imaging(CMR) in evaluating the perioperative risk of surgical treatment in patients of coronary artery disease and heart failure with reduced ejection fraction.Methods:A total of 78 patients diagnosed with CAD and HFrEF who underwent CABG in Beijing Anzhen Hospital from January 2018 to October 2021 were retrospectively enrolled. All patients underwent CMR examination before CABG. The perioperative data of the two groups were compared, and the risk factors that may lead to perioperative MACCE were analyzed by LASSO regression. Then, logistic regression was used to establish a prediction model and internal validation was performed to evaluate the diagnostic efficiency and accuracy of the model by Bootstrap method. Results:There were 24 patients(30.8%) with perioperative MACCE and 54 patients(69.2%) without perioperative MACCE. LASSO regression was used to screen out three factors related to the outcome. Multivariate logistic regression analysis showed that LGE in the third and eighth segment of left ventricle and diastolic radial strain rate were independent risk factors for perioperative MACCE. The area under the curve of the prediction model constructed with CMR was 0.799(95% CI: 0.696-0.901), so the discrimination was good. The calibration curve showed that the prediction curve was basically fit to the standard curve, and the Hosmer- Lemeshow test P=0.797, indicating high prediction accuracy. Conclusion:CMR is a valuable test for evaluating perioperative risk in patients with coronary heart disease complicated with HFrEF. To establish the risk prediction model combined with CMR can provide some reference for the assessment of perioperative risk in these patients undergoing surgical treatment.

Objective:To investigate the application value of cardiac magnetic resonance imaging(CMR) in evaluating the perioperative risk of surgical treatment in patients of coronary artery disease and heart failure with reduced ejection fraction.Methods:A total of 78 patients diagnosed with CAD and HFrEF who underwent CABG in Beijing Anzhen Hospital from January 2018 to October 2021 were retrospectively enrolled. All patients underwent CMR examination before CABG. The perioperative data of the two groups were compared, and the risk factors that may lead to perioperative MACCE were analyzed by LASSO regression. Then, logistic regression was used to establish a prediction model and internal validation was performed to evaluate the diagnostic efficiency and accuracy of the model by Bootstrap method. Results:There were 24 patients(30.8%) with perioperative MACCE and 54 patients(69.2%) without perioperative MACCE. LASSO regression was used to screen out three factors related to the outcome. Multivariate logistic regression analysis showed that LGE in the third and eighth segment of left ventricle and diastolic radial strain rate were independent risk factors for perioperative MACCE. The area under the curve of the prediction model constructed with CMR was 0.799(95% CI: 0.696-0.901), so the discrimination was good. The calibration curve showed that the prediction curve was basically fit to the standard curve, and the Hosmer- Lemeshow test P=0.797, indicating high prediction accuracy. Conclusion:CMR is a valuable test for evaluating perioperative risk in patients with coronary heart disease complicated with HFrEF. To establish the risk prediction model combined with CMR can provide some reference for the assessment of perioperative risk in these patients undergoing surgical treatment.

Objective:To determine the effects of preperitoneal balloon (PPB) tamponade with different volumes of fluid on hemodynamically unstable pelvic fracture-associated arterial and venous hemorrhage in a swine model.Methods:A model of open-book pelvic fracture with injuries to external iliac vessels was established in 18 female 12-month old Bama miniature pigs. After the successful establishment of hemodynamically unstable pelvic fracture with vascular injury was confirmed by contrast agent imaging, the animals were randomized into 3 even groups ( n=6): a control group (group C) subjected to PPB tamponade with 0 mL fluid injected, group T1 subjected to PPB tamponade with 500-mL fluid injected, and group T2 subjected to PPB tamponade with 1,000-mL fluid injected. The 3 groups were compared in terms of 60-min survival rate, balloon pressure, peritoneal pressure, bladder pressure, 70-min survival rate, blood loss, and infusion volume. Results:There was no statistically significant difference in the basic hemodynamic or other experimental indicators among the 3 groups before experiment, indicating comparability ( P>0.05). The 60-min survival rate in group T2 was 100.0% (6/6), significantly higher than those in group C and group T1 [0.0% (0/6), 0.0% (0/6)] ( P<0.05). After fluid injection, the balloon pressure and preperitoneal pressure in group T2 were respectively (127.2±4.7) mmHg and (34.5±3.6) mmHg, significantly higher than those in group T1 [(78.7±3.8) mmHg and (13.7±2.8) mmHg] and in group C [0 mmHg and (9.0±1.4) mmHg], and the 2 indicators in group T1 were significantly higher than those in group C (all P<0.05). After fluid injection, there was no statistically significant difference among groups C, T1, and T2 in bladder pressure [(6.7±1.0) mmHg, (5.8±1.9) mmHg, and (6.0±1.1) mmHg] or in bleeding volume [(1,163.0±191.3) mL, (1,212.0±148.4) mL, and (975.0±133.2) mL] (all P≥ 0.05). The infusion volume in group T1 [(1,250.0±225.8) mL] was significantly larger than that in group C [(951.7±177.8) mL] ( P<0.05). No colorectal or bladder injuries were found by the anatomy of the experimental animals in 3 groups. Conclusions:PPB tamponade with 1,000-mL fluid injected in a swine model can efficiently control pelvic fracture-associated arterial and venous hemorrhage, and increase the 60-min survival rate with no colorectal or bladder injuries.

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:To explore the effects of general anesthesia and combined spinal and epidural anesthesia on inflammatory factors and pain in patients with osteoarthritis after total knee arthroplasty.Methods:A total of 84 patients with osteoarthritis who underwent unilateral total knee arthroplasty in Hulunbuir People's Hospital from January 2020 to May 2021 were selected as the research subjects. They were randomly divided into general anesthesia group (40 cases) and combined spinal and epidural anesthesia group (44 cases). Venous blood samples of 5 ml were collected before operation and 6, 24, 48 hours after operation, and the contents of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6] in serum were determined by enzyme-linked immunosorbent assay (ELISA). The visual analogue pain scale (VAS) of the two groups at 30 min, 6, 24 and 48 hours after operation was compared.Results:At 6 and 24 hours after operation, TNF-α, IL-1β and IL-6 levels in the combined spinal and epidural anesthesia group were lower than those in the general anesthesia group ( t = 4.17, 3.85, 8.95, 10.98, 10.04, 9.87, P < 0.05). There were significant differences in the levels of TNF-α, IL-1β and IL-6 at different time points between the general anesthesia group and combined spinal and epidural anesthesia group ( F = 271.67, 149.26, 81.70, 189.36, 102.44, 157.32, P < 0.001). At 6 and 24 hours after operation, the VAS scores of patients in the combined spinal and epidural anesthesia group were significantly lower than those in the general anesthesia group ( t = 6.60, 3.66, P < 0.05). There were statistically significant differences in VSA scores between the two groups at different time points ( F = 67.47, 52.37, P < 0.05). Conclusion:The effect of combined spinal and epidural anesthesia is significantly higher than general anesthesia in inhibiting the expression of TNF-α, IL-1β and IL-6 in patients with osteoarthritis after operation, and the effect of analgesia is obvious.

Purpose: We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them. Methods: The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses. Results: Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64–0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%. Conclusion A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

Objective To explore the clinical and MRI features of central neurocytoma(CNC).Methods The clinical and MRI data of the pathologically confirmed CNC were retrospectively collected and compared,all the patients had undergone pre-surgery MRI plain and contrast enhanced scans.Patients were divided according to the location of the tumor as intra-lateral ventricle and ex-lateral ventricle group.Results Forty patients were finally enrolled,all tumors were solitary,39 of which were located in the ventricular system,including 2 7 cases located in lateral ventricle and 1 2 in the lateral ventricle,2 in third ventricle,5 in both lateral and third ventricle and 5 involving the whole ventricles;and 1 located in ex-ventricle(left temporal lobe).The tumors showed iso-intense on T1WI and T2WI with varying degrees of cystic degeneration.Hemorrhage was shown in 5 cases,calcification in 2 cases,markedly hyper-vascular enhancements were shown in 36 cases with 26 cases presented visible enhanced vessel sign.The comparison analysis between intra-and ex-lateral ventricle groups revealed that,the patients age,tumor size and Ki-67 expression were higher in ex-lateral ventricle group(P<0.05);hypervascular enhancement (P<0.05),gender ratio,cystic/cystic-solid appearance and vessel sigh(P>0.05)were lower than those in intra-lateral ventricle group.Conclusion CNC is typically located in lateral ventricle,with cystic and necrotic degeneration areas,hypervascular enhancement with visible vessels in solid portion on enhanced MR images;The ex-lateral ventricle CNC is rare,it commonly presents a larger tumor with high Ki-67 expression,and moderate enhancement with less visible vessels on enhanced MRI.