Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Interaction-driven Chern insulating phases in the α-T3 lattice with Rashba spin-orbit coupling.

The magnetic interaction is a necessary ingredient to break the time-reversal symmetry in realizing quantum anomalous Hall, or Chern insulating phases. Here, we study topological phases in the α-T3 model, a minimal theoretical model supporting the flat band, taking account of Rashba spin-orbit coupling and flat-band-induced spontaneous ferromagnetism. By analyzing the interaction-driven phase diagrams, band structures, topological edge states, and topological invariants, we demonstrate that this system offers a platform for realizing a wide range of phases, including normal insulators, semimetals, and Chern insulators. Uniquely, there exist both high-Chern-number insulators and valley-polarized Chern insulators. In the latter phase, edge channels exist in the single valley, leading to nearly 100% valley polarization. These findings demonstrate the potential of interaction-driven systems in realizing exotic phases and their promising role in future applications in topology electronics and valleytronics.

Inadvertent radical nephrectomy leads to worse prognosis in renal pelvic urothelial carcinoma patients: A propensity score-matched study.

Objective: To compare overall survival (OS) and cancer-specific survival (CSS) in renal pelvic urothelial carcinoma (RPUC) patients treated with radical nephroureterectomy (NU) and inadvertent radical nephrectomy (RN). Patients and methods: In this retrospective study, patients with RPUC who underwent NU or RN diagnosed between 2004 and 2017 were identified from the Surveillance, Epidemiology, and End Results database. To adjust the confounders, the propensity score-matched analysis was conducted. The Kaplan-Meier method and log-rank test were performed to explore the effect of different surgical methods on OS and CSS. Results: A total of 2197 cases were finally included in this analysis, among which, 187 (8.5%) patients were treated with RN and 2010 (91.5%) patients were treated with NU. Before matching, the survival analysis revealed that the OS (HR: 1.444, 95%CI: 1.197, 1.741) and CSS (HR: 1.522, 95%CI: 1.211, 1.914) of patients who received RN were worse than that of patients who received NU (p = 0.0001 and p = 0.0003, respectively). After matching, the RN group had a worse OS (HR: 1.298, 95%CI: 1.002, 1.682) than the NU group (p = 0.048). No significant difference was observed in CSS between the RN and NU groups (p = 0.282). The hierarchical analysis showed that there was no significant difference observed in OS and CSS in patients with tumor size ≤4.2 cm (p = 0.884 and p = 0.496, respectively). In tumor size >4.2 cm, both OS (HR: 1.545, 95%CI: 1.225, 1.948) and CSS (HR: 1.607, 95%CI: 1.233, 2.095) of patients who received RN were worse than those of patients who received NU (p = 0.0002 and p = 0.0005). Conclusion: RN could lead to worse oncological outcomes than NU in patients with renal pelvis urothelial carcinoma. Accurate diagnosis of renal pelvis urothelial carcinoma is extremely important.

Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach.

BACKGROUND: Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS. METHODS: Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database. Fifty-three rectal mucosa samples from 27 irritable bowel syndrome with diarrhea (IBS-D) patients and 40 samples from 21 healthy volunteers as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein-protein interaction network was constructed and visualized using STRING database and Cytoscape. RESULTS: The microarray analysis demonstrated a subset of genes (CCKBR, CCL13, ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients. CONCLUSIONS: Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.

Sulforaphane reduces apoptosis and oncosis along with protecting liver injury-induced ischemic reperfusion by activating the Nrf2/ARE pathway.

PURPOSE: The purpose of this study was to determine the effect of sulforaphane (SFN) on hepatic ischemia reperfusion injury (HIRI) and to explore the underlying mechanisms. METHODS: The rat model of HIRI was established. Thirty-two rats were randomly divided into sham (A), SFN (B), HIRI (C), and SFN + HIRI (D) groups. Animals in the HIRI and Sham groups were treated with equal volumes of the vehicle of SPF. Liver functions were evaluated by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver samples were collected for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels. Mitochondrial Na(+)-K(+)-ATPase and Ca(2+)-ATPase were measured by colorimetry. Expression levels of NQO1, Nrf2, and HO-1 in liver tissue were detected by western blot analysis. Additionally, oncosis and apoptosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis. RESULTS: The HIRI group showed a significant increase in serum levels of liver enzymes (ALT, AST) associated with histopathological damage in the liver. Pre-treatment with SFN could reduce the levels of MDA and MPO in liver tissue and improve the activities of SOD, GSH, GSH-Px, and mitochondrial Na(+)-K(+)-ATPase and Ca(2+)-ATPase in liver tissue. Moreover, SFN could still increase the expression of NQO1, Nrf2, and HO-1 in liver tissue and decrease the oncosis and apoptosis of liver cells. CONCLUSIONS: Pre-treatment with SFN could attenuate HIRI via the activation of Nrf2/ARE signaling pathways, ameliorate oxidative stress, and maintain the normal activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase, thus reducing the occurrence of cell oncosis and apoptosis. Therefore, SFN can be considered a potential candidate as an anti-ischemic medication to minimize HIRI.

[Effect of N-acetylcysteine on intestinal injury induced by cardiopulmonary bypass in rats].

OBJECTIVE: To observe the effect of N-acetylcysteine (NAC) on intestine injury induced by cardiopulmonary bypass (CPB) in rats. METHODS: Thirty-two rats were randomly divided into sham-operated group, NAC control group, CPB model group, and CPB plus NAC treatment group (n=8). In the latter two groups, the rats were subjected to CPB for 1 h. The rats received intraperitoneal injections of normal saline or NAC (0.5 g/kg) as appropriate for 3 successive days prior to CPB, and those in CPB plus NAC group were given NAC (100 mg/kg) in CPB prime followed by infusion at 20 mgsol;(kg·h) until the cessation of CPB. Intestinal and blood samples were collected 2 h after CPB for pathological analysis and measurement of intestinal concentrations of malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interlukin (IL)-6 and activity of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) and serum levels of diamine oxidase (DAO). RESULTS: Evident oxidative stress and pathological damages of the intestines were observed in rats after CPB. NAC treatment obviously alleviated intestinal damages induced by CPB, decreased the levels of intestinal MDA, TNF-α, IL-6 and serum DAO and increased activity of SOD, GSH, and GSH-Px in the intestines. CONCLUSION: Perioperative NAC treatment can alleviate intestinal injury induced by CPB in rats by suppressing oxidative stress and inflammatory response.

Treatment with Astragalus membranaceus produces antioxidative effects and attenuates intestinal mucosa injury induced by intestinal ischemia-reperfusion in rats.

Astragalus membranaceus, also known as huang qi, a traditional Chinese medicine, is often used in formulas for deficiency of vital energy characterized by limb weakness, pale face, and dizziness. Previous studies have shown that Astragalus membranaceus could attenuate intestinal ischemia-reperfusion injury induced by hemorrhagic shock in rats; however, the underlying mechanism still remains unclear. Using a hemorrhagic shock rat model to examine the effect of Astragalus membranaceus on intestinal mucosa injury induced by ischemia-reperfusion, we found that treatment (20 g crude drugs/kg, i.v.) produced antioxidative effects in the intestinal mucosa of rats after ischemia-reperfusion (p < 0.05). We also found that Astragalus membranaceus could partly attenuate intestinal mucosa ischemia-reperfusion injury (chiu's score, apoptosis index p < 0.05). These results suggest that Astragalus membranaceus reduces intestinal mucosa injury induced by ischemia-reperfusion in rats, at least in part, through its anti-oxidative effects.

[Effects of mechanical ventilation and controlled spontaneous respiration on pulmonary function during short duration of general anesthesia with tracheal intubation].

OBJECTIVE: To evaluate the effects of mechanical ventilation on pulmonary function during short duration of general anesthesia with tracheal intubation, and assess the safety of controlled spontaneous respiration during general anesthesia. METHODS: Fifty-three adult patients (aged 18-55 years, ASA physical status I-II) scheduled for elective unilateral tympanoplasty were randomly assigned into mechanical ventilation group (group M, n=28) and spontaneous respiration group (group S, n=25). Anesthesia induction was performed in group M with intravenous propofol (2 mg/kg), fentanyl (3 microg0.05). The pH and SpO(2) [ (97.9-/+1.00)% at the lowest] and PaO(2) in group S were significantly lower and the PaCO(2) was higher than those in group M (P<0.05). In group S, the pH values were 7.274-/+0.025 and 7.331-/+0.039, PaCO(2) values were 60-/+6 and 53-/+5 mmHg, and PETCO(2) values were 53-/+ 6 and 48-/+7 mmHg, and the PaO(2) values were 143-/+37 and 165-/+49 mmHg immediately and 150 min after the intubation, respectively. These values were considered safe under the concept of permissive hypercapnia. No significant differences were found in the P(A-a)DO(2), RI, VD/VT and TFC between or within the two groups (P>0.05), nor were moving, bucking, swallowing and awareness recorded during the surgical procedures. CONCLUSION: In essentially normal lungs, short-term mechanical ventilation during general anesthesia with tracheal intubation does not damage the lung functions, and spontaneous respiration can offer sufficient oxygen supply without causing harmful carbon dioxide retention.

Study on pretreatment of FPS-1 in rats with hepatic ischemia-reperfusion injury.

This study was designed to determine whether FPS-1, the water-soluble polysaccharide isolated from fuzi, protected against hepatic damage in hepatic ischemia-reperfusion injury in rats, and its mechanism. SD rats were subjected to 60 min of hepatic ischemia, followed by 120 min reperfusion. FPS-1 (160 mg/kg/day) was administered orally for 5 days before ischemia-reperfusion injury in treatment group. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (ALB) were assayed to evaluate liver functions. Liver samples were taken for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), that catalase (CAT) in liver. Na(+)-K(+)-ATPase and Ca(2+)-ATPase in mitochondria were measured with colorimetry method. Morphological changes were also investigated by using both light microscopy and electron microscopy (EM). In addition, apoptosis and oncosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis. Serum AST and ALT levels were elevated in groups exposed to ischemia-reperfusion (p < 0.05). Ischemia-reperfusion caused a marked increase in MDA level, and significant decreases in hepatic SOD and CAT (p < 0.05). Na(+)-K(+)-ATPase and Ca(2+)-ATPase were reduced in ischemia-reperfusion groups compared to the sham group (p < 0.05). Oncosis and apoptosis were also observed in ischemia-reperfusion groups. Pretreatment with FPS-1 reversed all these biochemical parameters as well as histological alterations, evidently by increased SOD, CAT, reduced MDA and histological scores compared to the model group (p < 0.05). FPS-1 could attenuate the necrotic states by the detection of immunofluorescent flow cytometry analysis. Pretreatment with FPS-1 reduced hepatic ischemia-reperfusion injury through its potent antioxidative effects and attenuation of necrotic states.

Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-kappaB pathways and mitochondrial protective mechanisms.

We had reported that increased levels of endogenous ghrelin during the progression of doxorubicin-induced cardiomyopathy and heart failure might provide a compensatory self-protective effect. We investigated which pathway(s) produced these protective effects in vitro. Primary cultured cardiomyocytes were induced with doxorubicin in the presence or absence of ghrelin or a tumor necrosis factor-alpha (TNF-alpha) antagonist (etanercept). Ghrelin up-regulated TNF-alpha in a time- and dose-dependent manner. It significantly reduced cell apoptosis and markers of oxidative stress, such as malondialdehyde (MDA) content and lactate dehydrogenase (LDH) activity; it also increased anti-oxidative enzyme activity such as superoxide dismutase (MnSOD) and catalase (CAT), retained mitochondrial membrane potential and energy metabolism compared with doxorubicin alone. Moreover, ghrelin increased mitochondrial anti-apoptosis related gene protein expression such as bcl-2 and MnSOD, reduced cytoplasmic cytochrome C (Cyt C) release and strengthened the activation of NF-kappaB. All these effects were abrogated by etanercept. This suggests ghrelin affects the TNF-alpha/NF-kappaB activation pathways, up-regulating TNF-alpha, to produce anti-oxidative and anti-apoptotic effects that protected cardiomyocytes from doxorubicin-induced cytotoxicity.

[A comparison of the metabolic effect of postoperative analgesia with lornoxicam and morphine or morphine on patients undergoing gastrointestinal carcinoma operation].

OBJECTIVE: To compare the metabolic effect of postoperative analgesia with lornoxicam/morphine or morphine on patients undergoing gastrointestinal carcinoma operation. METHODS: One hundred patients, undergone gastrointestinal carcinoma operations, were randomly assigned into two groups: group A received postoperative analgesia with lornoxicam/morphine and Group B with morphine alone. Parenteral nutrition with limited nitrogen resource was given to both groups. Visual analog scale (VAS), temperature and postoperative nitrogen balance were monitored postoperatively. The concentration of plasma cortisol , epinephrine, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured preoperatively and day 1, 3 postoperatively. RESULTS: VAS of two groups at 24 th, 48 th, 72 th after operation were similar (P>0.05). The temperature of two groups on the third postoperative day increased as compared to that before operation, and the temperature of group B on 1st and 3rd postoperative day [(37.8+/-0.6),(37.5+/-0.8)degrees C] were significantly higher than those of group A[(37.3+/-0.5)degrees C,(37.0+/-0.8)degrees C](P<0.05). Nitrogen balance within 3 days after operation were -7.5+/-3.2, -5.2+/-4.2, -3.1+/-1.2 in group A and -16.7+/-7.3, -10.5+/-6.1, -9.1+/-2.1 in group B (P<0.05). The post-operative plasma concentrations of cortisol and epinephrine increased significantly in both groups as compared to those examined preoperatively(P<0.05), but there was no significant difference between the two groups. However, the plasma concentrations of TNF-alpha and IL-6 in group B were significantly higher than those in group A(P<0.05). CONCLUSIONS: Postoperative analgesia with lornoxicam/morphine or morphine is able to produce an adequate postoperative analgesia to patients undergoing gastrointestinal carcinoma operation. Lornoxicam and morphine analgesia possesses a better metabolic intervention in decreasing the protein metabolism and improving the nitrogen balance.

[Effect of postoperative analgesia with flurbiprofen axetil and sufentanyl on metabolism of surgical patients with intestinal carcinoma].

OBJECTIVE: T To evaluate the effect of postoperative analgesia with flurbiprofen axetil combined with sufentanyl in modulating the metabolism of patients undergoing operations for intestinal carcinoma. METHODS: Eighty patients undergoing operations for intestinal carcinoma were randomly assigned into two groups, in group A, the patients received postoperative analgesia with flurbiprofen axetil combined with sufentanyl, and in group B, only sufentanyl was given. Parenteral nutrition with restricted nitrogen resource was given in both groups. The Visual Analog Scale (VAS), body temperature and postoperative nitrogen balance were monitored postoperatively, and the concentrations of plasma cortisol, epinephrine, tumour necrosis factor-alpha(TNF-alpha) and interleukin-6 (IL-6) were measured perioperatively. RESULTS: VAS at 24, 48, 72 h after operation were similar between the two groups (P>0.05). The changes in body temperature, nitrogen balance, TNF-alpha and IL-6 after operation were more obvious in group B than in group A, but significantly improved on postoperative day 3 (P<0.05) in the two groups. Flurbiprofen did not result in postoperative increase in cortisol and epinephrine. CONCLUSION: Postoperative analgesia with flurbiprofen axetil and sufentanyl or with sufentanyl alone produces similar postoperative analgesic effect in patients undergoing operation for intestinal carcinoma, but the former protocol offers better interventional effect on protein catabolism and promotes nitrogen balance.

[Analysis of factors leading to prescheduled analgesic withdrawal in patients with postoperative epidural analgesia].

OBJECTIVE: To analyze the factors leading to prescheduled analgesic withdrawal in patients with postoperative epidural analgesia. METHODS: A retrospective study of 4876 patients with postoperative epidural analgesia was conducted and the effect of analgesia and incidence of prescheduled analgesic withdrawal were recorded. The factors precipitating the occurrences of analgesic withdrawal and complications were analyzed. RESULTS: Early analgesic withdrawal occurred in 113 cases (2.3%), among which 74 (0.5%) were due to factors irrelevant to analgesic complications. Analgesia-related complications occurred in 578 patients, but only 39 (0.7%) of them needed discontinuation of the analgesics. CONCLUSION: Prescheduled analgesic withdrawal is predominantly due to technical inadequacies rather than complications arising from the analgesics, and improvement of the operation skills for postoperative analgesia may reduce early analgesia discontinuation and enhance the patients' satisfaction.

[Effects of Astragalus membranaceus injection on nitric oxide and endothelin concentration of intestinal mucosa after hemorrhage shock-reperfusion in rats].

OBJECTIVE: To observe the effects of Stragalus membranaceus injection on nitric oxide and endothelin levels of intestinal mucosa in reperfusion injury after hemorrhage shock. METHOD: 32 SD rats were randomly divided into four groups: normal group, model group, low dosage group, (treated with Astragalus membranaceus 10 g x kg(-1)); high dosage group (treated with Astragalus membranaceus 20 g x kg(-1)). Models of hemorrhagic shock for 60 minutes and reperfusion for 90 minutes were created. The animals were administrated 3 mL therapeutic solution before reperfusion. At the end of study, intestinal pathology was observed, and the concentration of lactic acid (LD), nitric oxide (NO), endothelin (ET) of intestinal mucosa were detected. RESULT: The intestinal pathology showed that intestinal mucosa epithelial cells damage in model group was severe, in low dosage group was medium, in high dosage group was slight, and no obvious damage was found in normal group. The concentration of LD and NO of small intestine mucous membrane in model group and low dosage group were significantly higher than those in high dosage group and normal group (P < 0.05), but there were no significant differences between high dosage group and normal group (P > 0.05). The concentration of ET of small intestine mucous membrane in model group was the highest of the four groups (P < 0.05). The concentration of ET in low dosage group was significantly higher than that in high dosage group and normal group (P < 0.05), but there were no significant differences between high dosage group and normal group (P > 0.05). CONCLUSION: Stragalus membranaceus injection can reduce small intestine mucous damage by protecting endothelium function in injury after hemorrhage shock-reperfusion.