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BACKGROUND: Antiapoptosis is a major factor in the resistance of tumor cells to chemotherapy and radiotherapy. Thus, activation of cell pyroptosis may be an effective option to deal with antiapoptotic cancers such as esophageal adenocarcinoma (EAC). METHODS: Differential expression of ubiquitin-like versus PHD and ring finger structural domain 1 (UHRF1) in EAC and near normal tissues was analyzed, as well as the prognostic impact on survival in EAC. Also, the same study was done for globular adiponectin (gAD). Simultaneously, the mRNA expression of UHRF1 was observed in different EAC cell lines. Real time cellular analysis (RTCA) was used to detect cell proliferation, and flow cytometry and inverted fluorescence microscopy were used to detect pyroptosis. Biocredit analysis was conducted to observe the correlation between UHRF1 and key pyroptosis proteins. OD values and CCK8 assay were used to determine the effect of miR-378a-3p on EAC cells. Quantitative real-time polymerase chain reaction and Western blot were used to detect the correlation between UHRF1, gAD, and miR-378a-3p in EAC cells. Moreover, in vivo and in vitro experiments were performed to detect the relevant effects on tumor migration and invasion after inhibiting UHRF1 expression. RESULTS: UHRF1 was negatively correlated with the survival of patients with EAC, while miR-378a-3p showed the opposite effect. Additionally, gAD promoted EAC cell pyroptosis, upregulated miR-378a-3p, and significantly inhibited the proliferation of EAC cells. gAD directly reduced UHRF1 expression in EAC cells by upregulating miR-378a-3p. In cell migration and invasion assays, inhibition of UHRF1 expression significantly suppressed EAC cell metastasis. In animal experiments, we again demonstrated that gAD induced pyroptosis in EAC cells by inhibiting the expression of UHRF1. CONCLUSION: gAD-induced upregulation of miR-378a-3p significantly inhibited the proliferation of EAC by targeting UHRF1. Therefore, gAD may serve as an alternative therapy for chemotherapy- and radiation-refractory EAC or other cancers with the same mechanism of pyroptosis action.
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【Objective】 To evaluate the clinical value of capsule endoscope in the diagnosis of unexplained abdominal pain. 【Methods】 We made a retrospective analysis of 191 patients with unexplained abdominal pain who sought medical help in our hospital and 25 normal controls. Capsule endoscopy was performed in both groups, small bowel lesions were detected, and clinical data were collected for further analysis. 【Results】 The total small bowel lesion detection rate was 52.87% (101/191) in abdominal pain (AP) patients and 20% (5/25) in the control group, respectively. The detection rate of significant findings (ulcers, erosions, polyps, diverticula, parasites, and neoplastic organisms) was only 16.23% (31/191) in AP patients. In the non-significant findings, no statistical difference in the detection rates for vascular malformation, capillary dilation, and lymphoid follicular hyperplasia were found between the two groups, while the detection rate of intestinal lymphangiectasia was significantly higher in the AP patients (23.56% vs. 4%, P<0.05, OR=7.089). 【Conclusion】 Capsule endoscopy can be an optional choice for diagnosis of unexplained abdominal pain, while the relationship between positive findings and abdominal pain should be further investigated.
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Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide. However, unlike that in female infertility, the role of CT infection in male infertility remains controversial. The objective of this retrospective study was to explore the impacts of CT infection in the genital tract on sperm quality, sperm acrosin activity, antisperm antibody levels, and inflammation in a large cohort of infertile males in China. A total of 7154 semen samples were collected from infertile male subjects, 416 of whom were CT positive (CT+ group) and 6738 of whom were CT negative (CT- group), in our hospital between January 2016 and December 2018. Routine semen parameters (semen volume, pH, sperm concentration, viability, motility, morphology, etc.), granulocyte elastase levels, antisperm antibody levels, and sperm acrosin activity were compared between the CT+ and CT- groups. Our results showed that CT infection was significantly correlated with an abnormally low semen volume, as well as an increased white blood cell count and granulocyte elastase level (all P < 0.05) in the semen of infertile males; other routine semen parameters were not negatively impacted. The antisperm antibody level and sperm acrosin activity were not affected by CT infection. These findings suggested that CT infection might contribute to inflammation and hypospermia but does not impair sperm viability, motility morphology, and acrosin activity or generate antisperm antibodies in the infertile males of China.
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Feminino , Humanos , Masculino , Chlamydia trachomatis , Genitália , Infertilidade Masculina/epidemiologia , Inflamação/epidemiologia , Estudos Retrospectivos , Sêmen , EspermatozoidesRESUMO
【Objective】 To study the diagnostic value of balloon expulsion test, anorectal manometry, and colonic transit test for detecting constipation with defecation disorders. 【Methods】 Outpatients with functional constipation were retrospectively analyzed and classified into dyssynergic defecation constipation and non-dyssynergic defecation constipation according to the Rome Ⅳ diagnostic criteria. We studied the differences in symptomatological characteristics and results of the three testing methods between the two groups of patients. 【Results】 Among the 48 patients with functional constipation included, there were 13 males (27.1%) and 35 females (72.9%) with an age of (44.8±12.3) years, including 32 patients (66.7%) with defecation disorder and 16 patients (33.3%) with non-defecation disorder. The percentage of anal distension was significantly higher in patients with dyssynergic defecation constipation than in those with non-dyssynergic defecation constipation (34.4% vs. 0.0%, P=0.021). All the three tests had diagnostic value for dyssynergic defecation constipation, but with low diagnostic agreement between the results of each test. The diagnostic sensitivity of anorectal manometry was 100%, but the specificity (56.3%) was low, and both the positive predictive value (82.1%) and the negative predictive value (100%) were higher; the diagnostic sensitivity (75.0%) and specificity (81.3%) of the balloon expulsion test were both higher. The Youden index of colonic transit test was the smallest. The anal resting pressure and maximum systolic pressure of dyssynergic defecation constipation were lower than those of non-dyssynergic defecation constipation (75.2 mmHg vs. 97.1 mmHg, 168.7 mmHg vs. 251.6 mmHg). The two types of constipation did not significantly differ in anorectal pressure gradients during simulated defecation or rectal sensory function. 【Conclusion】 The balloon expulsion test can be used as a primary screening test for constipation with defecation disorders, and anorectal manometry has the highest comprehensive diagnostic value, but there is a certain false positive rate, and the colonic transit test has the lowest diagnostic efficacy. Thus a comprehensive analysis of the patient’s symptoms and the results of different tests is needed in clinical practice.
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Objective To investigate the effect and mechanism of high concentration glucose on cholesterol absorption of human colon cancer epithelial Caco-2 cells.Methods The experimental study was used.(1) CCK-8 detected cell proliferation:the proliferation rate changes of Caco-2 cells were detected by CCK-8 when different concentrations (12.5,100.0,300.0,700.0,1 000.0,1 388.0 mmol/L) of glucose solution effects on Caco-2 cells in order to ensure the half hindering concentration of glucose concentration on Caco-2 cells.(2)Cholesterol absorption of Caco-2 cells was detected:Caco-2 cells were divided into the cholesterol group,cholesterol plus ezetimibe (cholesterol inhibitor) group and blank control group.Cholesterol group:100 μmol/L cholesterol solution and different concentrations (5.0,25.0,50.0 mmol/L) of glucose solution were added.Cholesterol plus ezetimibe group:100 μmol/L ezetimibe,100 μmol/L cholesterol solution and different concentrations (5.0,25.0,50.0 mmol/L) of glucose solution were added.Blank control group:DMEM culture medium and corresponding concentrations of DMSO were added.The cholesterol absorption amounts of Caco-2 cells were measured.(3) The relative expressions of ATP binding cassette G8 (ABCG8),ATP binding cassette G5 (ABCG5),Nickman-Pick CI Like 1 (NPC1L1) and scavenger receptor class B type Ⅰ (SR-B Ⅰ) were examined by Western blot in the different groups.Caco cells were divided into the glucose group,glucose plus ezetimibe group and control group.The different concentrations (5.0,25.0,50.0 mmol/L) of glucose solution were added into the glucose group,different concentrations (5.0,25.0,50.0 mmol/L) of glucose solution and 100 μmol/L ezetimibe were added into the glucose plus ezetimibe group,and 100 μmol/L ezetimibe were added into the control group.The relative expressions of ABCG8,ABCG5,NPC1L1 and SR-B Ⅰ were detected by Western blot.Measurement data were presented as (x) ±s,repeated measure variance analysis was used to perform variation trend test,and t test was utilized to conduct comparisons among groups.Results (1) CCK-8 results showed:proliferation rates of Caco-2 cells with the glucose solution concentration of 12.5,100.0,300.0,700.0,1 000.0 and 1 388.0 mmol/L were 1.380 ±0.043,1.238 ±0.072,0.736 ±0.035,0.336 ±0.021,0.316 ±0.020 and 0.288 ±0.010,respectively,with a statistically significant difference in the proliferation rates (F =11.019,P ＜ 0.05).The half hindering concentration of glucose solution on Caco-2 cells was 283.54 mmol/L.(2)Cholesterol absorption of Caco-2 cells:① the cholesterol absorption amounts of Caco-2 cells with the glucose solution concentration of 5.0,25.0 and 50.0 mmol/L were 0.282 ± 0.042,0.380 ± 0.063,0.390 ± 0.060 in the cholesterol group and 0.042 ± 0.012,0.197 ± 0.015,0.277 ± 0.029 in the cholesterol plus ezetimibe group,respectively,showing a statistically significant difference between the 2 groups (F =55.566,P ＜ 0.05).②There was a statistically significant difference in cholesterol absorption amounts of Caco-2 cells with different glucose solution concentration in the cholesterol group (F =79.117,P ＜ 0.05).The cholesterol absorption amounts of Caco-2 cells with the glucose solution concentrations of 5.0 mmol/L was lower than that with the glucose solution concentrations of 25.0 mmol/L and 50.0 mmol/L,respectively (t =11.207,11.532,P ＜0.05).There was no statistically significant difference in the cholesterol absorption amounts of Caco-2 cells between the glucose solution concentrations of 25.0 mmol/L and 50.0 mmol/L (t =12.389,P ＞ 0.05).③There were statistically significant differences in cholesterol absorption amounts of Caco-2 cells with the glucose concentration of 5.0 mmol/L and 25.0 mmol/L between cholesterol group and cholesterol plus ezetimibe group (t =10.908,10.644,P ＜ 0.05).(3) The results of Western blot showed:① the relative expression of NPC1L1 protein in Caco-2 cells with the glucose solution concentrations of 5.0,25.0 and 50.0 mmol/L were respectively 0.277 ±0.019,0.558 ±0.015,0.576 ±0.003 in the glucose group and 0.057 ±0.002,0.054 ±0.005,0.077 ±0.005 in the glucose plus ezetimibe group,showing a statistically significant difference (F =482.207,P ＜0.05).② The relative expression of NPC1L1 protein of Caco-2 cells with the different concentration of glucose solution in the glucose group were compared,with a statistically significant difference (F =8.112,P ＜ 0.05).There was a statistically significant difference in the relative expression of NPC1L1 protein in Caco-2 cells with the different concentration of glucose solution in the glucose plus ezetimibe group (F =11.708,P ＜ 0.05).③ The relative expression of NPC1L1 protein in Caco-2 cells with the glucose solution concentrations of 5.0,25.0 and 50.0 mmol/L in the glucose group was statistically different from that in the glucose plus ezetimibe group (t =8.112,11.708,13.920,P ＜ 0.05).Conclusion High concentration glucose solution could promote the reabsorption of cholesterol through increasing NPC1L1 protein expression in Caco-2 cells,and increase the risk of suffering from cholelithiasis in diabetes patients.
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BACKGROUND:Some studies have shown that more copy number variations are present in early passage human induced pluripotent stem cells than later passage human human induced pluripotent stem cells, their parental somatic fibroblasts or human embryonic stem cells. OBJECTIVE:To investigate whether the reprogramming process itself compromises genomic stability and further explore the efficiency of induced pluripotent stem cellestablishment. METHODS:Using high-resolution Affymetrix CytoScan HD array, we compared copy number variations and loss of heterozygosity in early passage induced pluripotent stem cells with their fibroblast cellorigins from genetic epilepsy patients. RESULTS AND CONCLUSION:Compared with somatic fibroblasts from genetic epilepsy patient, there was no difference in the loss of heterozygosity between the two types of cells, but more copy number variations were present in early passage human induced pluripotent stem cells which were characterized as microduplication and involved oncogenic genes. Results demonstrate the dynamic nature of genomic abnormalities during reprogramming process and the necessity of frequent monitoring human induced pluripotent stem cells to assure their genomic stability and clinical safety.
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Objective:To observe the effect of pioglitazone on carotid artery intima-media thickness (IMT) and plaque-positive rate in patients with metabolic syndrome, and to ifnd a new way to improve arterial remodeling in patients with metabolic syndrome. Methods:Patients with metabolic syndrome were randomly divided into a control group (n=60) and a pioglitazone group (n=61). All subjects received basic therapeutic measures, i.e, appropriate medication to control blood pressure, blood sugar and cholesterol. Pioglitazone (15 mg/d) was given to patients in the pioglitazone group, and placebo (vitamin C) in the control group for 24 weeks. Color doppler ultrasound was used to measure carotid artery IMT and plaque-positive rate of patients in the 2 groups atfer the intervention. Japan’s Hitachi 7600-020 automatic biochemical analyzer was used to measure fasting serumal triglycerides, total cholesterol, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acids, fasting blood glucose, 2-hour postprandial glucose and liver and kidney function, etc. The differences between groups after the intervention were analyzed and compared in IMT, plaque-positive rate and all blood biochemical indicators. Results:Atfer the intervention, compared with the control group, carotid artery plaque-positive rate and the levels of triglyceride and free fatty acid decreased in the pioglitazone group (P0.05). Conclusion:Pioglitazone intervention can significantly improve pathologic artery remodeling, and it can more effectively inhibit the arterial plaque-formation than basic therapeutic measures in patients with metabolic syndrome.
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Objective Toinvestigate the changes of liver and kidney function and morphology of the renal artery of the metabolic syndrome (MS) rats.Methods The rats were respectively fed with ordinary or high-fructose diet for 10 weeks,and then took the blood and anatomical observation,to explore the changes of liver and kidney function and morphology of the renal artery of the rats.Results The serum levels of ALT,AST,UA,BUN,CR in the control group and MS group were gradually increased with the feeding time.But those in MS rats were significantly increased than the control rats.MS rats showed dysfunction of liver and kidney,which similar to the clinical MS cases.Compared with the control group,the renal artery of MS rats had the same pathological changes as MS cases,presented with intima uneven thickening and structural disorder,medial smooth muscle cells hyperplasia to intimal,the internal elastic membrane with different degrees of damage and fracture,the film elastic fibers thickening and structural disorder,smooth muscle cell proliferation apparently,medial obvious thickening.Conclusion MS rats have mild dysfunction of liver and kidney and abnormal changes in intima and tunica media of renal artery.
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Objective To investigate the effects and mechanisms of rosiglitazone on the expressions of nuclear factor-κB and matrix metalloprotease (MMP-9) in peripheral blood monocyte-derived macrophages (MDMs) in patients with coronary heart disease. Method This was a clinical case-control study. Forty-eight actue coronary symdrome (ACS) patients (ACS group), and 20 patients with stable angina (SA) (control group) were collected. They were performed coronary arteriography in the Department of Cardiology of the Second Xiangya Hospital from March to April in 2007. Exclusion criteria included acute infection, trauma or surgery patients within four weeks, cerebral vascular accident, liver and kidney dysfunction, cancer, and so on. The peripheral blood mononuclear cells were isolated and transformed into MDMs with macrophage colony-stimulating factor treatment. The transformed MDMs were randomly assigned into subgrougs and incubated with 0 /μmol/L, 1 μmol/L, 10 μmol/L, 20 μmol/L of rosiglitazone respectively. The expressions of PPAR-γ mRNA, MMP-9 mRNA were determined by RT-PCR and nuclear factor-κB P65 (NF-KB P65) expression by immunohistochemistry. Multiple comparisons were examined for significant differences using analysis of variance (ANOVA). Results The basal expression of PPAR-y mRNA was lower, in contrast, the levels of NF-KB P65 and MMP-9 mRNA were higher in ACS group than control group. PPAR-γ mRNA expression were significantly upregulated in both ACS and control groups with rosiglitazone treatment. PPAR-γ mRNA expression was positive correlation, while the expressions of MMP-9 mRNA were negative correlation with the rosiglitazone concentration in the ACS group. Rosiglitazone inhibited the expression of NF-KB in a concentration-independent manner in ACS and control groups. Conclusions The expression of PPAR-y mRNA is inhibited, while the activity of NF-KB and expression of MMP-9 mRNA are enhanced in MDMs of ACS cases. Rosiglitazone intervention may inhibit NF-KB activity and MMP-9 expression by upregulation of PPAR-y expression in MDMS of patiens with ACS.
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Objective To investigate the role of Shenqihuang steady plaque caps (SQH) and simvastatin on stabilization of atherosclerosis plaque in rabbits whit atherosclerosis (AS). Methods Forty-five rabbits were randomly divided into five groups: normal food group (A), instability plaque group (B), SQH group (C), simvastatin group (D), SQH add simvastatin group. A group was fed with common feeds, and B, C, D, E groups were given high cholesterol feeds. An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented for 12 weeks in B, C, D, E groups. Then C, D, E groups received corresponding drugs. At the end of 24~(th) week, the drug were injected into the aortic segments rich in plaque. Two weeks later, the concentration in serum of lipids, vascular cellular adhesion molecule-1 (VCAM-1), intercellular cellular adhesion molecule-1 (ICAM-1) and high sensitivity C reaction protein (hs-CRP), and area of plaque, the thickness of endomembrane, ttmica media, fibrous cap were detected. Results Compared with B group, the concentration of VCAM-1, ICAM-1, hs-CRP and area of plaque, the thickness of endomembrane, tunica media in C, D and E groups were lower significantly, the thickness of fibrous cap was thicker significantly (P
