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.

Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting "Warburg effect" compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H

Transcuataneous electrical nerve stimulation (TENS) analgesia as a non-drug method has received people's more and more attention recently. Considering problems of existing products, such as unstable performance and unsatisfied effectiveness, we developed a new analgesia therapy system for delivery based on bio-feedback TENS in our laboratory. We proposed a new idea for stimulation signal design, that is, we modulated a middle frequency signal by a traditional low frequency TENS wave in the new system. We designed different prescription waves for pain relief during a uterine contraction or massage between contractions. In the end, a bio-feedback TENS method was proposed, in which the waveforms of stimulation signals were selected and their parameters were modified automatically based on feedback from uterine pressure, etc. It was proved through quality tests and clinical trials that the system had good performance and satisfied analgesia effectiveness.
Analgesia ; methods ; Biofeedback, Psychology ; methods ; Female ; Humans ; Pain Management ; Transcutaneous Electric Nerve Stimulation ; methods ; Uterine Contraction

Objective To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH),and to determine whether elevated levels of these biomarkers could predict development of early organ damage .Methods 56 PA patients ( the observation group) and 56 EH patients(the control group) matched for age,sex,blood pressure and duration of hypertension were included in this study .The plasma levels of biomarkers reflecting endothelial dysfunction [ von Willebrand factor (vWF),soluble intercellular adhesion molecule 1(sICAM-1),oxidized low density lipoprotein(ox-LDL)]were detec-ted and compared between PA and EH patients .The left ventricular mass index ( LVMI) determined by echocardio-graphy,24-hour urinary protein quantitative determination and urinary albumin excretion rate ( UAER) were analyzed to evaluate early organ damage .Results ( 1 ) In the observation group , the plasma markers of endothelial damage vWF (133.4 ±54.9)%,sICAM-1 (412.1 ±75.2)μg/L and ox-LDL (13.7 ±9.0) U/L levels were higher than those in the control group(t=4.642,3.955,2.843,all P<0.05),and the observation group had a higher 24 h urina-ry protein(t=2.042,P<0.05) and LVMI(t=7.235,P<0.05).(2)Correlation analysis showed that LVMI was positively correlated with PAC,ox-LDL,vWF (r=0.447,0.385,0.393,P=0.020,0.046,0.029),and was nega-tively correlated with admission blood K +(r=-0.294,P<0.05).UAER was positively correlated with PAC,vWF and sICAM-1 (r=0.622,0.389,0.499,all P<0.05),and was negatively correlated with admission blood K +(r=-0.314,P<0.05).Conclusion Patients with PA have severer endothelial dysfunction reflected by multiple bio-markers and earlier organ damage than patients with EH ,and plasma aldosterone concentration and multiple endotheli-al dysfunction biomarkers could independently predict early organ damage .