Objective To study the correlation between fractional excretion of uric acid (FEUA) and blood uric acid,body mass index (BMI),blood pressure,blood glucose,blood lipid and other metabolic factors in patients with primary gout.Methods Sixty-two patients with primary gout (gout group) and 32 healthy people (control group) were selected in this study.Gout group was divided into uric acid excretion decreasing group (FEUA ＜ 7％,29 cases),mixed group (7％ ≤FEUA ≤ 12％,25 cases) and uric acid production increasing group (FEUA ＞ 12％,8 cases) according to the level of FEUA.The fasting blood glucose (FPG),2-hour postprandial blood glucose (2 h PBG),blood lipid,serum creatinine,blood uric acid,glycosylated hemoglobin were tested.24 hours urine was collected and urinary uric acid and urinary creatinine was measured,FEUA was calculated and analyzed.Results BMI,mean arterial pressure,blood uric acid,glycosylated hemoglobin,total cholesterol,2 h PBG in gout group was higher than that in control group,and high density lipoprotein cholesterol,FEUA was lower than that in control group,and there was significant difference (P ＜ 0.05).There was no significant difference in age,FPG,low density lipoprotein cholesterol,triacylglycerol between two groups (P＞ 0.05).There was no significant difference in age,blood uric acid,FPG,2 h PBG,glycosylated hemoglobin,total cholesterol,low density lipoprotein cholesterol,high density hpoprotein cholesterol among uric acid excretion decreasing group,mixed group and uric acid production increasing group (P ＞ 0.05),and there was significant difference in BMI,mean arterial pressure,triacylglycerol,FEUA among three groups(P＜ 0.05).FEUA was negatively correlated with blood uric acid in control group and gout group (r =-3.900,-0.476,P ＜0.05).FEUA was positively correlated with 24 h urinary uric acid in gout group (r =0.465,P =0.001),and nagatively correlated with triacylglycerol (r =-0.304,P ＜ 0.05).Pearson analysis showed that FEUA was negatively correlated with blood uric acid in uric acid excretion decreasing group (FEUA ＜ 7％) (r =-0.392,P ＜ 0.05),FEUA was positively correlated with blood uric acid in non uric acid excretion decreasing group (FEUA ≥7％)(r =0.437,P ＜ 0.05),but 24 h urinary uric acid was not correlated with blood uric acid(P ＞ 0.05).Multi-stepwise regression analysis showed that blood uric acid,glycosylated hemoglobin,FEUA was significantly correlated with the onset of the gout (P ＜ 0.05).Conclusions Besides blood uric acid level,there are significant changes in primary gout in blood pressure,serum glucose and lipid levels.FEUA could be used to estimate the ability of renal excrete the uric acid.Mean arterial pressure,glycosylated hemoglobin and FEUA are the risk factors for gout.

AIM: To establish a quantitative measurement method of ECV-304 cell migration in a scratch wound model in vitro. METHODS: The method of ECV-304 cell scratch wound model was improved. The ECV-304 cell migration was measured quantitatively using a computer-assisted video microscopic method with image-analysis system. The effects of heparin and thrombospondin-1 on ECV-304 cell migration were observed in the scratch wound model in vitro. RESULTS: The average width and length of cell scratch wound was (0.95?0.08) mm and (51.20?3.40) mm respectively in 120 experiments. The peak of cell migration reached about 24 h after culture. The stimulated effect of heparin and inhibited effect of thrombospondin-1(TSP-1) on cell migration were observed. CONCLUSION: A quantitative measurement method of ECV-304 cell migration in vitro is established. The stimulated and inhibited effects on ECV-304 cell migration were proven respectively using this method.

Objective To study the effects on tissue CT number caused by scan protocols.Methods The phantom was repeatedly scanned in different protocols by changing only one of parameters,such as X-ray tube voltage,mAs and recon kernel,while other parameters were ketp unchanged.The CT number of different materials in phantom were measured and analyzed.Results The CT numbers of tissues changed remarkably with the tube voltage and had different relativity for different tissues.The CT numbers had positive correlation with kV for such maierials as polyethyle,lexan,perspex,but for teflon the correlation was negative.The mAs and recon kernel had no effects on CT number.Conclusions The CT number of tissue changes with scanning X-ray tube voltage,so the setting of scan parameters should be taken into account in image diagnosis and radiotherapy.

The data of a patient with autosomal dominant optic atrophy (ADOA) and chronic renal insufficiency caused by SSBP1 gene mutation in the Children′s Hospital Affiliated to Zhengzhou University in July 2021 was analyzed retrospectively.Literature was reviewed.The patient was a 10-year-old girl, who visited the hospital due to " growth retardation for the past 3 years and elevated serum creatinine (Scr) for the past 2 years" . On admission, the patient′s height was 130 cm (<10 th percentile of the same sex of healthy age) and her weight was 22 kg (<3 rd precentile of the same sex of healthy age). Lab examination showed that the level of blood urea nitrogen (BUN) was 16.3 mmol/L, Scr was 115.4 μmol/L, and the estimated glomerular filtration rate was 41 mL/(min·1.73 m 2). The patient was complicated with metabolic acidosis and mild anemia.Imaging findings showed small volume of both kidneys, increased background parenchymal enhancement, scattered spot-like hyperechoes and unclear boundary between the cortex and medulla.Additionally, the patient had a history of optic atrophy.Both the father and mother of the patient had no related phenotypes.The genetic test of the patient showed that c. 320G>A (p.R107Q) was a heterozygous missense mutation, which was spontaneous.A total of 5 English papers were retrieved.There were 8 kinds of SSBP1 gene mutations reported, including 7 heterozygous missense mutations [c.320G>A (p.Arg107Gln), c.119G>T (p.Gly40Val), c.331G>C (p.Glu111Gln), c.184A>G (p.Asn62Asp), c.113G>A (p.Arg38Gln), c.422G>A (p.Ser141Asn), c.79G>A (p.Glu27Lys)] and 1 homozygous mutation [c.394A>G (p.Ile132Val)]. Studies have established that almost all patients carrying SSBP1 mutations have manifestations of eye involvement, and that some patients are complicated with progressive deterioration of renal function, sensorineural deafness, growth retardation, and hypothyroidism.It suggests that SSBP1 gene mutation can cause ADOA.For patients with optic atrophy, whether they are complicated with hearing loss and growth retardation, renal morphology and renal function evaluation are recommended.Early genetic examination is helpful for diagnosis and treatment.

Mammalian carboxylesterases (CEs) are key enzymes from the serine hydrolase superfamily. In the human body, two predominant carboxylesterases (CES1 and CES2) have been identified and extensively studied over the past decade. These two enzymes play crucial roles in the metabolism of a wide variety of endogenous esters, ester-containing drugs and environmental toxicants. The key roles of CES in both human health and xenobiotic metabolism arouse great interest in the discovery of potent CES modulators to regulate endobiotic metabolism or to improve the efficacy of ester drugs. This review covers the structural and catalytic features of CES, tissue distributions, biological functions, genetic polymorphisms, substrate specificities and inhibitor properties of CES1 and CES2, as well as the significance and recent progress on the discovery of CES modulators. The information presented here will help pharmacologists explore the relevance of CES to human diseases or to assign the contribution of certain CES in xenobiotic metabolism. It will also facilitate medicinal chemistry efforts to design prodrugs activated by a given CES isoform, or to develop potent and selective modulators of CES for potential biomedical applications.

Drug-metabolizing enzymes (DMEs), a diverse group of enzymes responsible for the metabolic elimination of drugs and other xenobiotics, have been recognized as the critical determinants to drug safety and efficacy. Deciphering and understanding the key roles of individual DMEs in drug metabolism and toxicity, as well as characterizing the interactions of central DMEs with xenobiotics require reliable, practical and highly specific tools for sensing the activities of these enzymes in biological systems. In the last few decades, the scientists have developed a variety of optical substrates for sensing human DMEs, parts of them have been successfully used for studying target enzyme(s) in tissue preparations and living systems. Herein, molecular design principals and recent advances in the development and applications of optical substrates for human DMEs have been reviewed systematically. Furthermore, the challenges and future perspectives in this field are also highlighted. The presented information offers a group of practical approaches and imaging tools for sensing DMEs activities in complex biological systems, which strongly facilitates high-throughput screening the modulators of target DMEs and studies on drug/herb‒drug interactions, as well as promotes the fundamental researches for exploring the relevance of DMEs to human diseases and drug treatment outcomes.

BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms