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 explore clinical effect of open reduction and internal fixation with Henry's approach butterfly plate in treating double-column Die-punch fractures of distal radius. METHODS: From January 2018 to June 2021, 26 patients with double-column Die-column distal radius were treated with open reduction and internal fixation through Henry's surgical approach and using distal radius volar column plate(butterfly plate), including 14 males and 12 females, aged from 20 to 75 years old with an average age of (44.2±3.4) years old. Postopertaive complications were observed, Gartland-Werley score at 12 months after opertaion was used to evaluate wrist joint function. RESULTS: All 26 patients were followed up from 10 to 18 months with an average of(13.4±0.8) months. All fractures were obtained fracture union, the time ranged from 8.5 to 15.8 weeks with an average of (11.4±0.5) weeks. All incisions healed at stageⅠwithout infection, nerve injury and internal fixation failure occurred. Postoperative Gartland-Werley score at 12 months was (3.65±0.36), and 16 patients got excellent result, 8 good and 2 moderate. CONCLUSION Open reduction and internal fixation with butterfly plate for the treatment of double-column Die-punch fractures of the distal radius through volar Henry approach could obtain satisfactory clinical outcomes.
Adult ; Aged ; Animals ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; Radius/surgery* ; Radius Fractures/surgery* ; Range of Motion, Articular ; Treatment Outcome ; Wrist Joint

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ² test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.
Colectomy ; Colonic Neoplasms/surgery* ; Female ; Humans ; Laparoscopy ; Male ; Prognosis ; Propensity Score ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome

ObjectiveTo understand the mechanism of β-amyloid （Aβ）-induced neurotoxicity， this study aimed to investigate the effects and possible pathways of Aβ on apoptosis-related nuclear transcription forkhead protein O3a （FoxO3a） and postsynaptic density protein 95 （PSD95）. MethodsPC12 cells and neurons were treated with gradient concentrations （5， 10， 20 μmol/L） of Aβ_25-35 for 24 h， and the alterations of FoxO3a and PSD95 were detected by RT-PCR and Western blot. Immunofluorescence assay was used to detect the level of PSD95 in PC12 cells and the subcellular localization of FoxO3a in the cells. Then in rats injected with Aβ_25-35 and APP/PS1 transgenic mice， the changes of PSD95 and FoxO3a in brain tissue were investigated. Western Blot was used to detect the effects of Aβ on the phosphorylation of FoxO3a and protein kinase B （AKT） in vitro and in vivo. ResultsCompared with cells in the normal control group， the protein levels of PSD95 in the cells treated with Aβ_25-35 at the dosage of 20 μmol/L were down-regulated to （45.09±1.61）% （P=0.054 0）. Correspondingly， the protein levels of FoxO3a were increased to （228.70±20.44）% （F=17.48， P=0.021 0） when the cells were treated with 20 μmol/L of Aβ_25-35. In the primary cultured neurons， similar results were obtained. In addition， the results of immunofluorescence showed that Aβ_25-35 promoted the nuclear translocation of FoxO3a. The residence time of Aβ_25-35-injected group was （24.35 ±1.29） s （F=2.843， P=0.098） and the number of crossings was 2.53±0.49 （F=3.459， P=0.014 9） of rats in the water maze test. There was significant difference between the CTL group and Aβ_25-35-injected group （P<0.05）. The RT-PCR assay showed that the mRNA level of PSD95 in the hippocampus of rats treated with Aβ_25-35 was decreased to （58.40±8.28）% （F=1.193， P=0.010 1） of that in the CTL group， and the mRNA expression of FoxO3a was increased to （140.90±7.45）% （F=2.378， P=0.049 6）. In the brain tissue of 7-month-old APP/PS1 transgenic mice， the mRNA and protein levels of PSD95 were down-regulated to （60.89 ±1.53）% （F=20.05， P=0.008 8） and （59.63±13.55）% （F=8.496， P=0.044 5）. Meanwhile the mRNA and protein levels of FoxO3a were up-regulated to （172.4±4.87）% （F=2.351， P=0.000 4） and （235.00 ± 39.03）% （F=2.754， P=0.032 0）， respectively. After treatment with 20 μmol/L Aβ_25-35 for different times （5， 10， 20， 40 min）， the phosphorylation of FoxO3a and AKT in PC12 cells was decreased with time. The levels of phosphorylated AKT and FoxO3a in the brain tissue of APP/PS1 transgenic mice were decreased to （65.75±3.51）% （F=6.362， P=0.023 6） and （46.62 ± 9.64）% （F=8.562， P=0.007 9） when compared with mice in the control group. ConclusionsAβ can up-regulate the expression of nuclear transcription FoxO3a and down-regulate the change of PSD95 in both in vitro cell models and in vivo animal models. The possible mechanism is to reduce the phosphorylation level of FoxO3a and increase the expression of FoxO3a by dephosphorylating AKT.

BACKGROUND: We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice. METHODS: Intestinal epithelial CCL7 overexpression (CCL7) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: We found that the CCL7 mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7 mice compared to WT. Furthermore, HFD-fed CCL7 mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis. CONCLUSIONS Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

Objective:To explore the effect of early drinking and eating for gastric cancer patients with multimode health propaganda and education during postoperative Enhanced Recovery After Surgery (ERAS).Methods:Sixty patients who would received radical operation of gastric cancer were randomly divided into two groups:observation group (30 cases) and control group (30 cases).Patients in the observation group were employed the multi-mode health propaganda and education which were guided more detailed and quantitative regimens for early drinking and eating.Patients in the control group were carried out with routine methods.The compliance of postoperative drinking and eating,the rate of complications and patients satisfaction were compared between the two groups.Results:The compliance of postoperative drinking and eating of the observation group was significantly higher than that of the control group.Hospital patient satisfaction in health-education projects (19.50 ± 0.50) of the observation group was significantly higher than that (16.12 ± 3.21) of the control group (P ＜ 0.05).The rate of gastrointestinal complications in the observation patients was significantly lower,compared with that in the control patients (P ＜ 0.05).Conclusion:During the postoperative ERAS for gastric cancer patients,early drinking and eating guided by multi-mode health propaganda and education is safe and effective,for which could increase the postoperative compliance,decrease the rate of complication.It is worth promoting early quantitative drinking and eating after operation.

The central nervous system (CNS) plays a key regulatory role in glucose homeostasis. In particular, the brain is important in initiating and coordinating protective counterregulatory responses when blood glucose levels fall. This may due to the metabolic dependency of the CNS on glucose, and protection of food supply to the brain. In healthy subjects, blood glucose is normally maintained within a relatively narrow range. Hypoglycemia in diabetic patients can increase the risk of complications, such as heart disease and diabetic peripheral neuropathy. The clinical research finds that the use of traditional Chinese medicine (TCM) has a positive effect on the treatment of hypoglycemia. Here the authors reviewed the current understanding of sensing and counterregulatory responses to hypoglycemia, and discuss combining traditional Chinese and Western medicine and the theory of iatrogenic hypoglycemia in diabetes treatment. Furthermore, the authors clarify the feasibility of treating hypoglycemia on the basis of TCM theory and CNS and have an insight on its clinical practice.
Brain ; metabolism ; Central Nervous System ; metabolism ; Diabetes Mellitus ; metabolism ; therapy ; Hormones ; metabolism ; Humans ; Hypoglycemia ; metabolism ; therapy ; Medicine, Chinese Traditional

The aim of the present study was to investigate the effect of glucagon-like peptide-1 (GLP-1) on palmitate-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. HUVECs were cultured in vitro, and then treated by palmitate to induce apoptosis. Meanwhile, GLP-1 was added to explore its effect. After 24 h of the treatments, Caspase-3 activity and DNA fragmentation were measured using ELISA kits. Phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) expression was detected by Western blot. The results showed that incubating HUVECs with 0.125 mmol/L GLP-1 increased Caspase-3 activity and DNA fragmentation. GLP-1 significantly inhibited palmitate-induced increases of Caspase-3 activity and DNA fragmentation in a concentration-dependent manner. Moreover, GLP-1 inhibited the up-regulation of p-p38 MAPK expression induced by palmitate in HUVECs. These results suggest GLP-1 protects HUVECs against lipo-apoptosis, and this effect may be mediated through inhibiting p38 MAPK pathway.
Apoptosis ; Caspase 3 ; metabolism ; DNA Fragmentation ; Glucagon-Like Peptide 1 ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; MAP Kinase Signaling System ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases ; metabolism