Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system X_c^-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.
Breast Neoplasms/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Female ; Ferroptosis ; Glutathione/metabolism* ; Humans ; Iron/metabolism*

OBJECTIVE: To investigate the mechanistic basis for the attenuation of bone degeneration by edible bird's nest (EBN) in ovariectomized rats. METHODS: Forty-two female Sprage-Dawley rats were randomized into 7 groups (6 in each group). The ovariectomized (OVX) and OVX + 6%, 3%, and 1.5% EBN and OVX +estrogen groups were given standard rat chow alone, standard rat chow +6%, 3%, and 1.5% EBN, or standard rat chow +estrogen therapy (0.2mg/kg per day), respectively. The sham-operation group was surgically opened without removing the ovaries. The control group did not have any surgical intervention. After 12 weeks of intervention, blood samples were taken for serum estrogen, osteocalcin, and osteoprotegerin, as well as the measurement of magnesium, calcium abd zinc concentrations. While femurs were removed from the surrounding muscles to measure bone mass density using the X-ray edge detection technique, then collected for histology and estrogen receptor (ER) immunohistochemistry. RESULTS: Ovariectomy altered serum estrogen levels resulting in increased food intake and weight gain, while estrogen and EBN supplementation attenuated these changes. Ovariectomy also reduced bone ER expression and density, and the production of osteopcalcin and osteorotegerin, which are important pro-osteoplastic hormones that promote bone mineraliztion and density. Conversely, estrogen and EBN increased serum estrogen levels leading to increased bone ER expression, pro-osteoplastic hormone production and bone density (all P<0.05). CONCLUSION EBN could be used as a safe alternative to hormone replacement therapys for managing menopausal complications like bone degeneration.

Whether in the West or the East, the connection between the ear and the rest of the body has been explored for a long time. Especially in the past century or more, the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy, and finally the concept of transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed. The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear. In the past two decades, taVNS has been a topic of basic, clinical, and transformation research. It has been applied as an alternative to drug treatment for a variety of diseases. Based on the rapid understanding of the application of taVNS to human health and disease, some limitations in the development of this field have also been gradually exposed. Here, we comprehensively review the origin and research status of the field.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Objective: To summarize the clinical features and treatment status for elderly in-hospital patients with mitral regurgitation (MR). Methods: A single center retrospective study was conducted in 1 741 patients admitted in our hospital from 2014-05-01 to 2015-04-30 with echocardiography confirmed moderate to severe MR. The patients were divided into 2 groups: Elderly group, n=680(39.06%)patients≥60 years of age and Non-elderly group,n=1 061(60.94%)patients<60 years.Clinical features and treatment status were studied and compared between 2 groups. Results: The mean age in Elderly group was (66.98±5.94) years and the most common type was degenerative MR (41.18%). Compared with Non-elderly group, Elderly group had more patients combining coronary artery disease (37.79% vs 17.43% ), more risk factors of atherosclerosis such as hypertension (45.44% vs 25.17%), diabetes (19.56% vs 8.48%) and hyperglycemia (35.29% vs 19.51%) all P<0.05; Elderly group had the higher EuroSCORE Ⅱ score (5.54±2.42) vs (3.15±1.66), greater left ventricular end diastolic diameter (57.72±12.37) mm vs (57.33±10.19) mm and less patients combining multiple valve disease (35.59% vs 40.81%), less patients received surgical treatment (54.71% vs 63.9%), all P<0.05. The surgery procedures (mitral valve replacement or mitral-plasty) were similar between 2 groups; compared with Non-elderly group, Elderly group had the higher application rate of bio-prosthetic valve (53.88% vs 18.67%), P<0.001. Conclusion: About 40% in-hospital moderate to severe MR patients were the elderly crowd, the most common pathogenesis was degenerative changes which leaded the higher incidences of cardiac complications, worse cardiac function and the higher risk scores for surgical treatment, there were less patients received surgery.

Objective: To evaluate the efficiency and safety of low intensity conditional regimen for children with Fanconi anemia (FA) receiving allogenic hematopoietic stem cells transplantation (allo-HSCT). Methods: Four patients diagnosed as Fanconi anemia were enrolled in this study. One patient received HLA-identical sibling donor hematopoietic stem cell transplantation, two patients underwent unrelated donor matched (UD) HSCT, and one patient received unrelated cord blood transplantation. The conditional regimen consisted of Busulfan with low dose of cyclophosphamide. Results: All 4 cases succeeded in allo-HSCT. The median time for neutrophils engraftment was 11(9-15) day, median time to platelets (PLT) engraftment was 12 (8-28) day. One case occurred with grade I of aGVHD, 1 case with hemorrhagic cystitis. No patient happened with hepatic veno-occlusive disease (VOD). Conclusion: Low intensity of conditional regimen is efficient and safe which should be recommended for FA patients with HSCT.
Busulfan ; Fanconi Anemia ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning

Aneurysm, False ; etiology ; surgery ; Blood Loss, Surgical ; Carcinoma ; Carotid Arteries ; Carotid Artery Diseases ; etiology ; surgery ; Humans ; Nasopharyngeal Neoplasms ; radiotherapy ; Rupture

Objective To investigate the association between arsenic(+3 oxidation state) methyltransferase (AS3MT) genetic polymorphism and susceptibility to endemic arsenism.Methods Polymerase chain reactionrestriction fragment length polymorphism-single strand conformation polymorphism(PCR-RFLP-SSCP) technology was performed to detect mutations of AS3MT gene intron 8 and exon 9 in genome DNA of the 79 cases and 110 controls.PCR products with abnormal band forms were further sequenced to find the types and sites of mutation.Chi-square test and multivariate Logistic analyses were conducted.Results The incidence of the 9149 base mutation(A→C) in AS3MT gene intron 8(AS3MT-9149) in case group(19.0％,15/79) was lower than that in control group (23.6％,26/110).The incidence of the codon 287 mutation(ATG→AT/CG) in AS3MT gene exon 9(AS3MT-287)in case group(10.1％,8/79) was lower than that in control group (11.8％,13/110).However,statistical analysis indicated no significant difference in both mutations between two groups[AS3MT-9149:odds ratio(OR) =0.59,95％ confidence interval(CI):0.26-1.31,P =0.195; AS3MT-287:OR =0.85,95％ CI:0.32-230,P =0.751].Conclusions There are no significant association between the genetic polymorphisms of AS3MT-9149,AS3MT-287 and the susceptibility to endemic arsenism.Similarly,due to small sample amount,we can not exclude the possibility that these gene polymorphisms are related to susceptibility to endemic arsenism.

BACKGROUNDWhile intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection.

METHODSAn injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package.

RESULTSIn the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P < 0.05). In further paired comparisons of the CSSSI group vs. modeling control/sodium hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P < 0.05), whereas sodium hyaluronate vs. sinomenine hydrochloride comparison failed to reach significance (P > 0.05).

CONCLUSIONSCSSSI has a sustained-release effect on sinomenine hydrochloride. Intra-articular injection of CSSSI was significantly better than the sole sodium hyaluronate or sinomenine hydrochloride for the treatment of osteoarthritis in a rabbit model.

Animals ; Hyaluronic Acid ; administration & dosage ; therapeutic use ; Injections, Intra-Articular ; Male ; Morphinans ; administration & dosage ; therapeutic use ; Osteoarthritis ; drug therapy ; Rabbits ; Random Allocation