ObjectiveTo investigate the association of BANK1 single nucleotide polymorphisms (SNPs) with rheumatoid arthritis(RA) in Chinese Han. MethodsTwo hundreds and twenty-one RA patients and 310 healthy controls who were Chinses Han population from Huashan Hopital and Changzheng Hospital in Shanghai,China were included.DNAs were extracted from peripheral whole blood for study.Samples were genotyped for three variants rs10516487,rs17266594 and rs3733197 in BANK1 by unlabelled probe high resolution melting (HRM) assay.The genotype frequencies of the detected polymorphisms were analyzed in relation to RA and the production of autoantibodies in RA patients.ResultsThe Tr genotype frequency was much higher in RA patients than in healthy controls(X2=6.241,P=0.044).The frequencies of rs10516487 G allele,rs17266594 T allele and rs3733197 G allele were increased among RA patients compared with healthy controls,although they didn't reach statistical significance.The rs10516487 and rs17266594 were found in strong linkage disequilibrium(D'=0.993,r2=0.985).And also the major TGG haplotype of 3-SNP was significantly associated with RA patients[P=0.037,OR =1.345,95％CI (1.018-1.776)].ConclusionBANK1 rs17266594 polymorphism is susceptible to RA,while rs10516487 and rs17266594 are linked in Chinese Han population.BANK1 SNPs TGG haplotype may contribute to RA susceptibility,too.

Effective doctor-patient communication not only affects the doctor-patient relationship,but also affects the normal medical practice.Johari window is referred to as theself consciousness discovery-feedback model or information exchange process management tool.This article introduces the relationship between self-exposure and experience feedback by doctors and patients.As a skill and theory about communication,Johari widow can help doctors to better understand their patients and to improve their ability of communication.

There is evidence that the myocytes produce dynorphin and dynorphin-like peptides, which are kappa opioid receptor (kappa-OR) agonists. Activation of kappa-OR, a dominant opioid receptor in the heart, alters the cardiac function in vivo and in vitro. The observations suggest that the endogenous kappa-opioid peptides may act as autocrines or paracrine in regulation of cardiac functions. Myocardial ischemia is a common cause of heart disorders, which is manifested in decreased myocardial performance, arrhythmia and infarct. When myocardial ischemia occurs, the sympathetic discharge increases, which in turn increases the work-load and oxygen consumption. This exacerbates the situation induced by ischemia. One of the mechanisms with which the body protects against ischemia-induced injury/arrhythmia is inhibition of stimulation of beta-adrenoceptor (beta-AR), the receptor mediating the actions of sympathetic stimulation. kappa-Opioids inhibit the beta-AR activation. The inhibition of the beta-AR activation is due to inhibition of Gs-protein and to a lesser extent the adenylyl cyclase of the signaling pathway mediating beta-AR stimulation by a pertussis sensitive G-protein that mediates kappa-OR activation. Another mechanism against ischemia-induced injury is preconditioning, which is defined as prior exposures to ischemia or other insults make the heart more tolerant to subsequent and more severe insults. Protection occurs immediately or 1-3 days after preconditioning. kappa-OR mediates protection of preconditioning with ischemia or metabolic inhibition, one of the consequences of ischemia, in the heart. Activation of kappa-OR by U50488H, a selective kappa-OR agonist (pharmacological preconditioning with U50488H, UP), activates protein kinase C (PKC), opens K(ATP) channels and increases the production of heat shock proteins. Blockade of PKC, or closing of the K(ATP) channels or inhibition of the synthesis of the heat shock protein abolishes the cardioprotection of UP. The findings indicate the important roles of PKC, the K(ATP) channels and the heat shock protein in cardioprotection of UP. In addition, UP also attenuates the Ca(2+) overload, a precipitating cause of cardiac injury, induced by ischemic insults, indicating that UP may confer cardioprotection via at least partly attenuating the Ca(2+) overload. Most interestingly, blockade of the K(ATP) channels with channel blockers, that abolishes the delayed cardioprotection of UP, also attenuates the inhibitory effect of UP on Ca(2+) overload, suggesting that the cardioprotective effect of opening of the K(ATP) channels may be due at least partly to the prevention/attenuation of Ca(2+) overload.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Calcium ; metabolism ; Cardiotonic Agents ; Humans ; Ischemic Preconditioning, Myocardial ; Myocardial Ischemia ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; prevention & control ; Receptors, Adrenergic, beta ; physiology ; Receptors, Opioid, kappa ; agonists ; physiology ; Signal Transduction

Objective To understand the correlation of enterovirus 71 (EV71), P-selectin glycoprotein ligand-1 (PSG L-1), and scavenger receptor B2 (SCARB2) and to explore the possible pathway and mechanismof EV71 infection by observing the expression of EV71, PSG L-1 and SCARB2 in tissues of infants with brain stemencephalitis. Methods T he organs and tissues of infants with EV71-VP1 positivi-ty in their brain stems were chosen. Expression and distribution of EV71-VP1, PSG L-1, and SCARB2 were detected and compared by immunohistochemistry. Results Strong staining of EV71-VP1 was ob-served in the neuron, glial cells, the inflammatory cells of perivascular cuffing, parietal cells of the gas-tric fundus gland while alveolar macrophages, intestinal gland epitheliumcells, mucosa lymphoid nodule and lymphocyte of palatine tonsil showed moderate staining and weak staining were displayed in mesen-teric lymph nodes and lymphocyte of spleen. PSG L-1 expression was detected in parietal cells of the gastric fundus gland, tonsillar crypt squamous epithelium, alveolar macrophages and leukocytes in each tissue. SCARB2 expression was observed in all the above tissues except the intestines and spleen. Con-clusion T he distribution of EV71 correlates with SCARB2 expression. SCARB2 plays an important role in virus infection and replication. Stomach may be an important site for EV71 replication.

OBJECTIVETo investigate the presence of tight junction (TJ) changes of the intestinal mucosa, and elucidate the possible mechanism for changes in bowel evacuation in patients with irritable bowel syndrome (IBS).

METHODSIn 10 normal control subjects, 10 patients with constipation predominant IBS (C-IBS) and 10 with diarrhea predominant IBS (D-IBS), biopsies were taken from the terminal ileum and ascending colon. Lanthanum nitrate tracing electron microscope and cytochemical technique were employed to observe TJ changes in the intestinal mucosa.

RESULTSLike the control subjects, C-IBS patients had normal TJ structure in the intestinal mucosa, whereas D-IBS patients exhibited some abnormalities in TJ structure either in their terminal ileum (7 in 10) or ascending colon (8 in 10), revealed by TJ gap widening with lanthanum nitrate extravasation into the surrounding tissue. Such changes were also observed in 3 of the 4 patients with a history of acute infectious diarrhea.

CONCLUSIONThe changes in the intestinal mucosal TJ structure and function might contribute to altered bowel evacuation in patients with irritable bowel syndrome.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Intestinal Mucosa ; cytology ; pathology ; ultrastructure ; Irritable Bowel Syndrome ; pathology ; Male ; Microscopy, Electron ; Middle Aged ; Tight Junctions ; pathology ; ultrastructure ; Young Adult

Objective To identify the therapeutic effect and safety of anterograde flexibleureteroscopy on the treatment of upper -middle ureteral calculi.Methods The clinical data of 47 patients who underwent anterograde flexible ureteroscopy for the treatment of upper -middle ureteral calculi in our center were retrospectively reviewed. During the 47 patients,28 cases were men,19 cases were women.Age ranged from 20 to 68 years.The diameter of calculi ranged from 8 to 22mm(mean =14 mm).Results The flexible ureteroscopic lithotripsy procedure were successful in all the cases.The mean operative time was (65.3 ±8.5)min.The mean hospital stay was 8 days.The average blood loss was less than 50mL.The initial stone -free rate was 93.62%(44 /47).No severe complications occurred intraoperative and postoperative.Conclusion Anterograde flexible ureteroscope has good therapeutic effect in treating upper -middle ureteral calculi.It is safe and effective procedure,with less complication and a high calculus removing rate.The surgical methods is worthy of clinical application.

Background/Aims: Since the use of dexlansoprazole in Asian subjects with gastroesophageal reflux disease (GERD) has not been adequately characterized, this study was conducted to evaluate the efficacy and safety of dexlansoprazole modified-release in Asian subjects with non-erosive reflux disease (NERD) and erosive esophagitis (EE). Methods: In this phase 4, open-label, non-randomized, uncontrolled, multicenter, multi-country study sponsored by Takeda, subjects aged ≥ 20 years with persistent typical GERD symptoms for at least 6 months underwent endoscopy. Based on endoscopic findings, they were assigned to either dexlansoprazole modified-release 30 mg once-daily for 4 weeks (NERD group) or dexlansoprazole modified-release 60 mg once-daily for 8 weeks (EE group). The primary endpoint was the percentage of days that subjects did not experience any 24- hour heartburn or acid regurgitation. Results: Of the 445 subjects screened from Hong Kong, South Korea, and Taiwan, 208 were enrolled in the NERD group (mean age: 53.6 years, male: 34.6%) and 88 in the EE group (mean age: 51.7 years, male: 55.7%). Over the treatment period, the median percentage of days that subjects did not experience any 24-hour heartburn or acid regurgitation was 26.9% and 65.5% in the NERD and EE groups, respectively; for nighttime heartburn or acid regurgitation the proportions were 59.3% and 83.3%, respectively. The treatment was well tolerated with low incidence of treatment-related adverse events in NERD and EE groups (6.7% and 5.7%, respectively). Conclusion In Asian patients with GERD, treatment with dexlansoprazole modified-release indicates a favorable efficacy and safety profile in relieving heartburn and acid regurgitation symptoms.

In recent years, iron has been regarded as a common pathological feature of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Friedreich's ataxia (FRDA). A number of genes involved in iron transport, storage and regulation have been found associated with initiation and progression of neurodegeneration. However, whether iron abnormalities represent a primary or secondary event still remains unknown. Due to the limitation in transgenic rodent model construction and transfection systems, the progress in unraveling the pathogenic role of different iron-related proteins in neurodegenerative diseases has been slow. Drosophila melanogaster, a simple organism which has a shorter lifespan and smaller genome with many conserved genes, and captures many features of human nervous system and neurodegeneration, may help speed up the progress. The characteristics that spatial- and temporal-specific transgenic Drosophila can be easily constructed and raised in large quantity with phenotype easily determined turn Drosophila into an excellent in vivo genetic system for screening iron-related modifiers in different neurodegenerative conditions and hence provide a better picture about the pathogenic contribution of different iron-related protein abnormalities. It is believed that identification of important iron-related genes that can largely stop or even reverse degenerative process in Drosophila models may lead to development of novel therapeutic strategies against neurodegenerative diseases.
Alzheimer Disease ; physiopathology ; Animals ; Disease Models, Animal ; Drosophila melanogaster ; Friedreich Ataxia ; physiopathology ; Humans ; Iron ; Neurodegenerative Diseases ; physiopathology ; Parkinson Disease ; physiopathology

OBJECTIVETo investigate the changes of intestinal mucosal tight junction proteins claudin-1, -3, -4 in patients with irritable bowel syndrome (IBS), and elucidate its possible role in the bowel evacuation habit changes and formation in these patients.

METHODSWestern blotting was employed to determine tight junction protein claudin-1,-3,-4 levels in the intestinal mucosa of patients in the control group, diarrhea-predominant IBS (D-IBS) group and constipation-predominant IBS (C-IBS) group.

RESULTSCompared with the control group, D-IBS patients showed significantly decreased claudin-1 protein levels in both the small intestinal and colonic mucosae (P<0.05), whereas C-IBS patients had significantly elevated claudin-1 protein levels (P<0.05). No significant difference was found in claudin-3 protein expression in the both small intestinal and colonic mucosae between the D-IBS group and the control group (P>0.05), but claudin-3 protein level was shown to increase significantly in C-IBS patients (P<0.05). Claudin-4 protein followed the same pattern of alteration as claudin-1.

CONCLUSIONDown-regulated claudin-1 and -4 expressions can be associated with bowel evacuation habit changes and formation in patients with D-IBS, but up-regulated claudin-1, -3 and -4 expressions may relate to such bowel changes in patients with C-IBS.

Adolescent ; Adult ; Aged ; Animals ; Blotting, Western ; Case-Control Studies ; Claudin-1 ; Claudin-3 ; Claudin-4 ; Colon ; metabolism ; pathology ; Female ; Gene Expression Regulation ; Humans ; Intestinal Mucosa ; metabolism ; pathology ; Irritable Bowel Syndrome ; metabolism ; pathology ; Male ; Membrane Proteins ; metabolism ; Middle Aged ; Tight Junctions ; metabolism ; Young Adult

To investigate the effects of 2-(4-methoxycarbonyl-2-tetradecyloxyphenyl)carbamoylbenzoic acid (CX09040) on protecting pancreatic β cells, the β cell dysfunction model mice were induced by injection of alloxan into the caudal vein of ICR mice, and were treated with compound CX09040. Liraglutide was used as the positive control drug. The amount and the size of islets observed in pathological sections were calculated to evaluate the β cell mass; the glucose stimulated insulin secretion (GSIS) test was applied to estimate the β cell secretary function; the oral glucose tolerance test (OGTT) was taken to observe the glucose metabolism in mice; the expressions of protein in pancreas were detected by Western blotting. The effects on the target protein tyrosine phosphatase 1B (PTP1B) were assessed by the PTP1B activities of both recombinant protein and the intracellular enzyme, and by the PTP1B expression in the pancreas of mice, separately. As the results, with the treatment of CX09040 in alloxan-induced β cell dysfunction mice, the islet amount (P<0.05) and size (P<0.05) increased significantly, the changes of serum insulin in GSIS (P<0.01) and the values of acute insulin response (AIR, P<0.01) were enhanced, compared to those in model group; the impaired glucose tolerance was also ameliorated by CX09040 with the decrease of the values of area under curve (AUC, P<0.01). The activation of the signaling pathways related to β cell proliferation was enhanced by increasing the levels of p-Akt/Akt (P<0.01), p-FoxO1/FoxOl (P<0.001) and PDX-1 (P<0.01). The effects of CX09040 on PTP1B were observed by inhibiting the recombinant hPTP1B activity with IC50 value of 2.78x 10(-7) mol.L-1, reducing the intracellular PTP1B activity of 72.8% (P<0.001), suppressing the PTP1B expression (P<0.001) and up-regulating p-IRβ/IRβ (P<0.01) in pancreas of the β cell dysfunction mice, separately. In conclusion, compound CX09040 showed significant protection effects against the dysfunction of β cell of mice by enlarging the pancreatic β cell mass and increasing the glucose-induced insulin secretion; its major mechanism may be the inhibition on target PTP1B and the succedent up-regulation of β cell proliferation.
Alloxan ; Animals ; Benzoates ; pharmacology ; Biological Assay ; Disease Models, Animal ; Glucose ; metabolism ; Glucose Tolerance Test ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Liraglutide ; pharmacology ; Mice ; Mice, Inbred ICR ; Molecular Weight ; Pancreas ; drug effects ; enzymology ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; Signal Transduction