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

In this paper, Asarum polysaccharides(AP) were extracted, and its composition was analyzed to study the activity against H1 N1 influenza virus in vitro and its intervention effect on mice with kidney Yang deficiency syndrome. AP was prepared by the strategy of water extraction and alcohol precipitation, the content was determined, and its monosaccharide composition was analyzed. The cell Real-time monitoring system and Reed-Muench model were adopted to evaluate the antiviral activity of AP in vitro. And the mouse model of kidney Yang deficiency syndrome was established in vivo to compare the efficacy of Mahuang Xixin Fuzi Decoction(MXF) and AP. MXF group and AP group were treated with clinical equivalent doses of 1.8 g·kg~(-1)·d~(-1) and 0.077 g·kg~(-1)·d~(-1) respectively, once a day for 6 consecutive days. Real-time PCR was used to detect the relative expression of M gene of H1 N1 influenza virus and cytokines in lung tissue. The content of AP in Asarum was 25.22%, and the protein content was 0.8%. And the monosaccharide composition was identified as L-rhamnose, D-arabinose, D-xylose, D-glucose, D-galactose and D-mannose. TI values of Tamiflu, MXF and AP were 30.00, 8.06 and 10.33, respectively. Three different doses of AP could significantly reduce the concentration of virus in supernatant. Compared with the model mice, lung indexes of MXF group and AP group decreased significantly(P<0.05), and the relative expression of M gene decreased significantly(P<0.05). The relative expressions of IL-10 and IFN-γ were up-regulated to varying degrees, while the relative gene expressions of IL-1β, IL-6 and MCP-1 were down-regulated to different degrees. In addition, AP could significantly enhance the expression of TNF-α(P<0.01). AP had a good anti-influenza virus activity in vitro, and could protect mice with kidney Yang deficiency syndrome by reducing the viral load in lung tissue, decreasing inflammation damage in lung tissue, and regulating the expression of inflammatory cytokines. Compared with the prescription of MXF, AP had a better antiviral activity.
Animals ; Antiviral Agents/therapeutic use* ; Asarum ; Cytokines/genetics* ; Drugs, Chinese Herbal ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/genetics* ; Lung ; Mice ; Polysaccharides

OBJECTIVE: To investigate the effect of Bmi-1 expression on the chemosensitivity of THP-1 cells and its relative mechanism. METHODS: The pGenesil-2-Bmi-1 1 siRNA, p-MSCV-Bmi-1 plasmid was transfected into THP-1 cells to reduce or increase the expression of Bmi-1. The expression of Bmi-1 mRNA and protein was verified by PCR and Western blot. The effect of camptothecin (CPT) on the proliferation and chemosensitivity of THP-1 cells affected by Bmi-1 gene were detected by MTT assay. The expression of DNA double-strand breaks marker-γ-H2AX was detected by immunofluorescence assay. Mitochondrial membrane potential and apoptosis were observed by flow cytometry. The expression of Cytochrome C, Caspase 3, Bax and BCL-2 was detected by Western blot. RESULTS: Silencing Bmi-1 could inhibit proliferation and enhance the sensitivity of THP-1 cells to CPT, while overexpressed Bmi-1 could promote the cell proliferation and attenucate sensitivity of THP-1 cells to CPT. Silencing Bmi-1 could enhance CPT-induced DNA double-strand breaks, decrease mitochondrial membrane potential and promote CPT-induced apoptosis. While increasing Bmi-1 gene expression could attenuate CPT-induced DNA double-strand breaks, enhamce mitochondrial membrane potential and significantly reduce CPT-induced apoptosis of cells. CONCLUSION Bmi-1 expression could influence the sensitivity of THP-1 cells to CPT, and its relative mechanism may relate to DNA double-strand breaks and endogenous apoptotic pathways.
Apoptosis ; Camptothecin/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; THP-1 Cells

Bronchoalveolar Lavage Fluid/virology* ; COVID-19/virology* ; Feces/virology* ; Genome, Viral ; Humans ; Mouth Mucosa/virology* ; Multiplex Polymerase Chain Reaction ; Nasal Mucosa/virology* ; SARS-CoV-2/genetics* ; Sputum/virology* ; Whole Genome Sequencing

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.

Water-soluble polysaccharides from traditional Chinese medicine have properties of complex structure and high molecular, resulting in hardly complete their structural characterization.However, a "bottom-up" approach could solve this problem.Glehniae Radix extract was extracted with hot water and then precipitated by 40% ethanol to obtain Glehniae Radix polysaccharides (RGP). Subsequently, a partial acid hydrolysis method was carried out and the effects of acid concentration, time and temperature on hydrolysis were investigated. Under the optimum hydrolysis condition (1.5 mol•L⁻¹ trifluoroacetic acid, 4 h, and 80 ℃), RGP were hydrolyzed to characteristic oligosaccharide fragments. Futher, a hydrophilic liquid chromatography- mass spectrometry method was used for the separation and structural characterization of the polysaccharide hydrolysates. According to MS and MS/MS analysis of several standard disaccharides, a method for determining the type of polysaccharide glycosidic linkage by mass spectrometry was established. The results showed that the polysaccharide hydrolysates were linear glucan containing 1, 4-glycosidic bonds. And gluco-oligosaccharides with the degrees of polymerization (DP) of 4-11 were obtained after partial acid hydrolysis.

Objective To discuss the effect and mechanism of miR-34a on the proliferation, apoptosis and invasion of laryngeal carcinoma cells. Methods The laryngeal squamous carcinoma Hep2 cells were transiently transfected with miR-34a mimics and miR-34a NC. The MTT, colony-forming assay, Hoechst staining and AnnexinV-PI double staining flow cytometry were employed to detect the effect of miR-34a on the viability and apoptosis of laryngeal squamous carcinoma Hep2 cells; Transwell assay to defect the effect of miR-34a on the migration and invasion of laryngeal squamous carcinoma Hep2 cells; western blot and RT-PCR assay to defect the effect of miR-34a mimics on the expression of survivin and Ki-67 mRNA in laryngeal squamous carcinoma Hep2 cells. Results Compared with miR-34a NC group, the cell viability in miR-34 mimics group was significantly decreased (P < 0.01), the cell apoptosis rate was significantly increased (P < 0.01), the abilities of cell migration and invasion were significantly reduced (P < 0.01) and the expression of survivin and Ki-67 mRNA was significantly decreased (P < 0.01). Conclusions The increased expression of miR-34a can induce the apoptosis of Hep2 laryngeal carcinoma cells and inhibit the cell proliferation and invasion, which is related to the down-regulated expression of survivin and Ki-67.

OBJECTIVE: To establish the method to analyze γ-hydroxybutyric acid (GHB) and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) in urine through LC-MS/MS and provide evidence for related cases. METHODS: GHB-d6 and MOR-d3 were used as the internal standard. The urine sample was separated by LC after protein precipitation with methanol. The electrospray ion source was for ionization. Each compound was detected through multiple-reaction monitoring (MRM) mode. RESULTS: The limits of detection of GHB and its precursors 1,4-BD and GBL were 0.1, 0.1 and 2 μg/mL. The accuracy was 87.6%-98.1%. The intra-day and inter-day precisions were less than 15% and matrix effects were higher than 80%. CONCLUSION The method is high sensitive, simple, rapid, specific and with high reliability. This study has provided technical support and basic data for forensic cases involving GHB.
4-Butyrolactone/urine* ; Butylene Glycols/urine* ; Chromatography, Liquid ; Forensic Sciences ; Humans ; Hydroxybutyrates/urine* ; Mass Spectrometry ; Reproducibility of Results ; Tandem Mass Spectrometry

OBJECTIVE: To compare the efficacy and safety of bevacizumab plus FOLFIRI program or FOLFOX program for metastatic colorectal cancer.

OBJECTIVETo compare the performance of full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in the assessment of the lesions in dense breast, and to estimate the difference in diagnosis of breast disease by FFDM images alone and FFDM plus DBT images.

METHODSAccording to the breast imaging reporting and data system (BIRADS), 134 patients were selected. The morphology of the lesions shown on FFDM and DBT were evaluated and compared, and the maximum diameter of the lesions was measured. At first, doctors made the diagnosis of a patient by reading FFDM only. Then they made another diagnosis by combining with DBT images of the same patient. The two diagnoses were compared and analyzed according to the pathology results.

RESULTSOne hundred and thirty-four patients were included in this study, and all of them were confirmed by histology (65 benign cases, 69 malignant cases). DBT could show more details about the morphology of the lesions, including the border of the masses, spiculation and vessels. The numbers of those signs detected by DBT were 46, 30 and 3, respectively, while only 33 case with circumscribed masses and 14 cases with spiculation were detected by FFDM. Only the difference of spiculation in heterogeneously dense breast detected by DBT and FFDM was statistically significant (P < 0.05). Of the cases with calcifications, DBT images (reconstructed as a 1-mm-thick slice) showed calcifications superior to FFDM in 2 cases, equal to FFDM in 23 cases, and inferior to FFDM in 11 cases. The difference was statistically significant (P < 0.05). But when thickness was changed into 1 cm, the visibility of calcifications in those cases was equal between FFDM and DBT. The maximum diameter of lesions was 2.46 ± 1.64 cm in DBT image, and 2.58 ± 1.62 cm in FFDM image, with a significant difference (P < 0.05). Comparing with reading FFDM images only, the accuracy of FFDM combining with DBT was increased from 88.8% to 91.8%. For FFDM, the AUC of ROC was 0.887, while for DBT it was increased to 0.912, with a non-significant difference (P > 0.05).

CONCLUSIONSDBT is superior to FFDM in the morphological characterization and small calcification in the lesions in dense breast. Combining FFDM and DBT improves the accuracy of diagnosis, but the difference is not statistically significant.

Adolescent ; Adult ; Breast Diseases ; diagnostic imaging ; Breast Neoplasms ; diagnostic imaging ; Calcinosis ; diagnostic imaging ; Carcinoma in Situ ; diagnostic imaging ; Carcinoma, Ductal, Breast ; diagnostic imaging ; Female ; Fibroadenoma ; diagnostic imaging ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Mammography ; methods ; Middle Aged ; Radiographic Image Enhancement ; Tomography, X-Ray Computed ; Young Adult