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Objective:To investigate the incidence and influential factors of hyperuricemia in older adult patients who live in the sanatorium and to improve the prevention and treatment of hyperuricemia people.Methods:A total of 800 older adult patients living in Wuyunshan Sanatorium between June 2017 and December 2019 were recruited for this study. The prevalence of hyperuricemia was determined as per the diagnostic criteria of hyperuricemia. These patients were divided into control and hyperuricemia groups according to whether they had hyperuricemia. General data, health status, physical examination, and laboratory indices were compared between the two groups. The influential factors of hyperuricemia were analyzed using the logistic regression analysis method.Results:The incidence of hyperuricemia in older adult patients living in the sanatorium was 18% (144/800). There was significant difference in the prevalence of hyperuricemia between male and female older adults [22.17% (104/469) vs. (12.08%) (40/331), χ2 = 13.38, P < 0.001]. The incidence of hyperuricemia was significantly higher in male older adults aged 60-90 years than in female older adults at the same age brackets [18.50% (59/319) vs. 5.48% (12/219), χ2 = 19.20, P < 0.001]. The overall prevalence of hyperuricemia and the prevalences of hyperuricemia in male and female older adults significantly increased with aging ( Z = 30.47, 11.92, 24.81, P < 0.001). There were significant differences in age, sex, alcohol consumption, urinary protein-positive, exercise, the prevalences of hypertriglyceridemia, hypercholesterolemia, and renal insufficiency between the control and hyperuricemia groups ( χ2/ t = 2.36, 19.41, 41.18, 10.11, 50.42, 8.24, 6.43, 8.59, all P < 0.05). Age, alcohol consumption, hypercholesterolemia and renal insufficiency were independent risk factors of hyperuricemia in older adults living in sanatorium ( OR = 2.07, 2.54, 2.31, 2.76, 95% CI = 1.218-3.541, 1.740-3.729, 1.538-3.468, 1.920-3.974). Exercise was a protective factor of hyperuricemia ( OR = 0.49, 95% CI = 0.356-0.694). Conclusion:Older adults living in sanatorium have a high incidence of hyperuricemia. Prevention and treatment of hyperuricemia should be strengthened in older adults who have a high risk for hyperuricemia to reduce the incidence of hyperuricemia.
ABSTRACT
Streptococcus pyogenes Cas9 (SpCas9) has become a powerful genome editing tool, but has a limited range of recognizable protospacer adjacent motifs (PAMs) and shows off-target effects. To address these issues, we present a rational approach to optimize the xCas9 mutant derived from SpCas9 by directed evolution. Firstly, energy minimization with the Rosetta program was applied to optimize the three-dimensional structure of Cas9 to obtain the lowest energy conformation. Subsequently, combinatorial mutations were designed based on the mutations sites of xCas9 acquired during the directed evolution. Finally, optimal mutants were selected from the designed mutants by free energy ranking and subjected to experimental verification. A new mutant yCas9 (262A/324R/409N/480K/543D/694L/1219T) with multiple PAM recognition ability and low off-target effects was obtained and verified by DNA cleavage experiments. This mutant recognizes the NG, GAA and GAT PAMs and shows low off-target DNA cleavage activity guided by mismatched sgRNA, thus provides a gene editing tool with potential applications in biomedical field. Furthermore, we performed molecular dynamics simulations on the structures of SpCas9, xCas9 and yCas9 to reveal the mechanisms of their PAM recognition and off-target effects. These may provide theoretical guidance for further optimization and modification of CRISPR/Cas9 proteins.
Subject(s)
CRISPR-Associated Protein 9/metabolism , CRISPR-Cas Systems/genetics , Clustered Regularly Interspaced Short Palindromic Repeats , Gene Editing , /genetics , Streptococcus pyogenes/metabolismABSTRACT
Objective To investigate the clinical efficacy of nimesulide in the treatment of chronic periodontitis patients,and analyze the effect of IL-8 and TNF-αlevels in the gingival sulcus fluid.Methods 88 patients with chronic periodontitis in our hospital between June 2014 to December 2015 were divided into control group and observation group by the random number method, 44 cases in each group, the control group patients were given metronidazole treatment, observation group patients were given nimesulide treatment,two groups therapeutic effect and the incidence of adverse reactions were observed, compared two groups of patients before and after treatment in gingival sulcus fluid IL-8 and TNF-αlevel, compared sulcus bleeding index (SBI), plaque index (PLI) and clinical attachment level (CAL),before and after treatment two weeks and four weeks of probing depth (PD) of two groups.Results The total effective rate of observation group patients was 95.55%, significantly higher than the control group patients’total efficiency (81.82%) (χ2 =4.06, P=0.04), after treatment in the observation group gingival sulcus fluid IL-8 factor and TNF-αlevels were significantly lower than the control group (P<0.05), After 2 weeks and 4 weeks of treatment, PD, SBI and CAL indicators observation group were significantly lower than the control group ( P <0.05 ) , the incidence of adverse reactions of observation group patients was 4.55%, significantly lower than the incidence of adverse reactions in control group patients(22.73%)(χ2 =6.18, P=0.01).Conclusion Nimesulide in the treatment of chronic periodontitis with a highly efficient clinical efficacy, while reducing gastrointestinal side effects, etc., can effectively reduce the gingival sulcus fluid IL-8 and TNF-αlevels, ease clinical symptoms, is a highly effective treatment.
ABSTRACT
Objective To investigate the effects of glucagon-like peptide-1(GLP-1)on the expression of apoptosis-related molecules including programmed cell death 5(PDCD-5)gene in pancreatic ? cells induced by proinflammatory cytokines.Methods Mouse islet ?-cell line NIT-1 was incubated for 24 h with cytokine mixture(Mix)in the absence or presence of GLP-1.The apoptotic cells were assayed by flow cytometry after stained with annexin V-FITC and propidium iodide(PI).The expressions of PDCD5,Fas,and caspase 3 were detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blot.Results The number of both annexin V single positive cells and annexin V/PI double positive cells significantly increased in the cells treated with 30 U/mL interleukin-1?(IL-1?)+ 100 U/mL interferon-?(IFN-?)+ 100 U/mL tumor necrosis factor-?(TNF-?).The expressions of PDCD5,Fas,and caspase 3 at both mRNA and protein levels were upregulated in the cells exposed to the cytokines.The above-mentioned effects of the cytokines were reversed by 10 nmol/L of GLP-1.Conclusion These data show that the proinflammatory cytokines cause pancreatic ? cell apoptosis via activation of PDCD5 signal pathway and that GLP-1 inhibits the upregulation of PDCD5 expression and the subsequent event of apoptosis induced by the cytokines.