Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

[Objective] To investigate the causal relationship between the relative intake of dietary components (including carbohydrate, added sugar, protein, and fat) and kidney stones using two sample Mendelian randomization (MR). [Methods] The genetic instrumental variables (IVs) from genome-wide association study (GWAS) statistics, exposure-related summary data from the SSGAC genome study, and kidney stone data from the Finn Gen Consortium were collected, which were then analyzed with inverse variance weighting (IVW). The MR results and sensitivity were assessed with MR-Egger, weighted median, MR-PRESSO test, Cochran's Q test, leave-one analysis, and Steiger filter. [Results] IVW results showed that the relative intake of carbohydrate (OR=2.01, 95%CI: 1.02-3.96, P=0.042) and added sugar (OR=2.07, 95%CI: 1.00-4.29, P=0.049) had a causal relationship and were risk factors for the development of kidney stones.Relative intake of protein (OR=0.70, 95%CI: 0.38-1.29, P=0.249) and fat (OR=0.79, 95%CI: 0.27-2.35, P=0.671) were not associated with kidney stones.Sensitivity analysis showed no heterogeneity or pleiotropy (P>0.05). [Conclusion] Relative intake of carbohydrate and added sugar are risk factors for kidney stones, suggesting that limiting carbohydrate and added sugar intake may prevent the development of kidney stones.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

Humans ; Retrospective Studies ; Transcatheter Aortic Valve Replacement/adverse effects* ; Risk Assessment ; China ; Prognosis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Risk Factors ; Aortic Valve

Objective: To explore the optimization of CT urography imaging parameters and the control measures of radiation dose to patients with different body mass index. Methods: A total of 133 patients who were required to undergo CT urography were prospectively selected in terms of three different types of CT urography scan; firstly, conventional parameter scan (120 kV, CARE Dose4D); secondly, low kV scan (BMI ≤ 22.9∶80 kV, 22.9 < BMI < 30∶100 kV, BMI ≥ 30∶120 kV, CARE Dose4D) and thirdly, low mAs scan (120 kV, 40% reduction in mAs on CARE Dose4D). Noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of all images were measured as objective evaluation indicators of image quality. The subjective evaluation of the images was performed by two radiologists who had been working for more than five years using a double-blind method and a 5-score system evaluation. The effective dose values (CTDI_vol, DLP, E) in each group were measured. Results: Patients′ effective dose was decreased by 77.7% in 80 kV group and 38.3% in 100 kV group, with a statistical difference between the two groups (Z=-3.330, -5.559, P<0.05). There was a statistically significant difference in renal cortex noise, SNR, CNR and ureteral noise between the 80 kV scan and the routine scan (Z=-3.705-2.392, P<0.05), but no significant difference in ureteral SNR, CNR and renal pelvis noise, SNR, CNR (P>0.05). There was a statistically significant difference in renal cortex noise and SNR between the 100 kV scan group and the routine scan group (Z=-5.096, -3.566, P<0.05), but no statistical difference in renal cortex CNR, renal pelvis and ureteral noise, SNR, CNR(Z=-5.086, -5.912, -2.842, P>0.05). The effective dose from low mAs scan in the three types of patients was decreased by 38.3%, 32.0%, and 34.7%, respectively, with a statistical difference between them (P <0.05). There was no significant difference in noise, SNR, and CNR between renal cortex, renal pelvis and ureter (P>0.05) besides ureteral CNR in the 22.9 < BMI < 30 group (Z=-2.587, P<0.05). The subjective evaluation scores of all images were greater than 3 points. Conclusions In this study, the scan method for low kV and low mAs used for patients with different body mass index can effectively reduce the radiation dose to patients and meet the requirements of clinical diagnosis.

Objective We aimed to analyze the clinical efficacy and treatment-related complications in patients with T4besophageal squamous cell carcinoma (SCC) who received concurrent CRT,and to explore the potential prognostic factors related to survival. Methods Between 2010 and 2015,143 patients with T4b esophageal SCC treated with CRT were analyzed, including 71% patients with trachea and/or bronchus invasion and 44% patients with aorta and/or large vessel invasion. The median radiation dose was 60 Gy ( range, 44-68 Gy ) with conventional fractionation, including 69 patients ( 48%) treated with three-dimensional conformal radiotherapy and 74 patients ( 52%) treated with intensity-modulated radiotherapy. All patients received concurrent platinum-based chemotherapy during radiotherapy. Kaplan-Meier method was used to analyze the survival,the log-rank test was used to examine group differences,and the Cox regression model was used for multivariate analysis. Results The median overall survival ( OS) time for the whole cohort was 12. 2 months. The 2-and 3-year OS rates were 34% and 29%,respectively. A total of 51 patients experienced ≥2 severe non-hematological complications,including 42 esophageal fistula,6 pneumonia,and 3 esophageal hemorrhage. Patients with severe complications showed significantly worse survival than those without complications (6. 9 months vs.20. 4 months,P＜0. 01).Multivariate analysis revealed that TNM stage and severe complications were independent prognostic factors for OS. Conclusions Patients with T4b esophageal SCC who received CRT showed satisfactory survival but with high risk of severe complications. Therefore,prevention and treatment of severe complications is the key to improve efficacy.

Objective To study the effect of amelogenin (AML)on the migration,adhesion and proliferation of periodontal ligament stem cells (PDLSCs).Methods STRO-1 +PDLSCs were selected by Flow cytometer.The transwell system was used to detect the effect of AML on migration of PDLSCs.Cells attachment assay was used to detect the effect of AML on adhesion of PDLSCs.MTT was used to detect the effect of AML on the proliferation of PDLSCs.Results The results of transwell showed that AML could induce the migration of PDLSCs with positive correlation.Cells attachment assay showed that the adhesion of PDLSCs was effected by AML as well,and the effect was in-creased with the extension of incubation time.Results of MTT showed that AML could promote the proliferation of PDLSCs in a dose depend-ent manner.Conclusion AML could increase the proliferation,adhesion and migration potential of PDLSCs.

Objective The purpose of this study was to evaluate the practicability and efficiency of iFlow assistant function in lower extremity vascular disease angioplasty.Methods Retrospective analysis to 22 patients with lower extremity vascular disease in our single center from Septmber 2013 to November 2013, 19 males and 3 females with mean age(66.31 ± 7.46)years, iFlow technology was utilized to analyze the Region Of Interest(ROI) Peak Time(PeakTime) in pre-and post-angioplasty of lower extremity artery and assessed the state of vessel stenosis and blood flow perfusion, as well Doppler ultrasound in postoperative was used to double identify iFlow results.The results of vessel lesion, such as state of stenosis and occlusion were diagnosed by two senior doctors individually, as well as ROI Peak Time was recorded by technician.Results The iFlow technique performed that the ROI PeakTime in the region of interest was significantly decreased in postoperative in comparison to pre-angioplasty [(0.48 ± 0.39) s vs.(1.32 ± 0.60) s, t =8.836, P ＜ 0.001].The Doppler ultrasound in postoperative showed that the ankle-brachial index was significantly increased compared within preoperative (0.97 ± 0.16 vs.0.49 ± 0.11, t =-10.205, P ＜ 0.001).The results of iFlow technique in intraoperative were consistent with those of Doppler ultrasound in postoperative.Conclusion iFlow technique is effective to evaluate hemodynamic change of blood flow in vessel lesion in pre-and postangioplasty, which is assistive technique to assess the efficiency and prognosis in angioplasty.