Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, distributing in a variety of tissues, especially in excitable cells such as heart cells and many kinds of neurons, have an important role in the modulation of heart rate and neuronal excitability. Different from typical voltage-gated sodium channels and potassium channels, HCN channels were evoked inward currents when the cell was hyperpolarized. More and more recent studies have disclosed that HCN channels play important roles in the nervous system, which were linked with its special electrophysiological features as well as its regulatory effect on the cellular membrane excitability. HCN channels could be modulated by many factors including both extracellular molecules and intracellular signaling cascades, which made its functions complicated in the different condition. Based on its role, HCN channels are presumed to be a promising target for chronic pain and brain disorders. In this paper, we will focus on the advancement of roles of HCN channels in the neural system as well as its complex modulator factors.
Cyclic Nucleotide-Gated Cation Channels ; physiology ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; physiology ; Membrane Potentials ; Neurons ; physiology ; Potassium Channels ; physiology

Adolescent ; Adult ; Cause of Death ; Child ; Female ; Hematologic Neoplasms ; mortality ; surgery ; Hematopoietic Stem Cell Transplantation ; mortality ; Humans ; Male ; Middle Aged ; Tissue Donors ; Young Adult

Objective To evaluate the clinical value of liquid-based thinprep cytology test (TCT) and human papillomavirus (HPV) in cervical lesions diagnosis.Methods 525 patients with TCT was inflammation and abnormalities had HPV testing and colposcopy with biopsy analysis.Results Histopathological diagnosis as CIN Ⅰ or CIN Ⅰ above cases percentage of TCT of ASCUS,LSIL,HSIL,and cancer cases were 55 ％ (160/290),88 ％ (99/113),92 ％ (24/26) and 100 ％ (4/4),Pathological diagnosis as inflammation and glandular phosphate in 441 cases of this TCT-positive patients were 148 patients,false positive 34 ％.TCT-negative patients,pathologically confirmed of CIN in 84 cases patients with moderate to severe cervical erosion or cervical polyps were 22 cases,26 ％ TCT false negative.They had statistically significance (x2 =815.4,P =0.000).74 ％ HPV positive patients diagnosed as CIN Ⅰ or CIN Ⅰ above (x2 =104.94,P =0.000).Diagnosed as CIN Ⅰ cases in less than 30 years old accounted for 62 ％ (61/98),CIN Ⅱ and above for only 38 ％ (37/98) and without cancer.But the CIN Ⅰ in above 30 age group was significantly reduced to only 37 ％ (81/217),CIN Ⅱ and above was significantly increased to 63 ％ (136/217),and cancer rate increased (x2 =63.71,P =0.012).Histopathological diagnosed as CIN Ⅰ case were 26 ％ (83/315) of cervical smooth,74 ％ (232/315) of cervical erosion; 14 cases of cancer occurred in patients with cervical erosion.It was statistically significant (x2 =39.9,P =0.014).Conclusion TCT and HPV for screening of cervical lesions play an important role in cervical lesions screening.

Objective To explore the roles of MircroRNA-217 ( Mir-217 ) , silent information regulator 1 (Sirt1), and hypoxia-inducible factor-1α(HIF-1α)in high glucose-induced inflammation and fibrosis in rat glomerular mesangial cells( RMCs) . Methods RMCs were pre-incubated with a Sirt1 activator resveratrol prior to high glucose treatment or transfected with Sirt1 small interfering RNA( siRNA) , HIF-1αsiRNA, and Mir-217 inhibitor. Real-time PCR was used to analyze the expressions of Mir-217, Sirt1 mRNA, and HIF-1α mRNA; Western blot was used to observe the protein expressions of Sirt1, HIF-1α, connective tissue growth factor(CTGF), endothelin-1(ET-1), and fibronectin( FN) . Enzyme-linked immunosorbent assay was applied to detect protein expression of transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF). Results High glucose increased Mir-217, HIF-1α, CTGF, ET-1, FN, TGF-β1, and VEGF expressions(all P<0. 01), while decreased Sirt1 expression. In addition, Mir-217 gene silencing or 25μmol/L resveratrol suppressed high glucose-stimulated expressions of HIF-1α, CTGF, endothelin-1, FN, TGF-β1, and VEGF(all P<0. 01). Conclusion Mir-217 mediates high glucose-induced inflammation and fibrosis in RMCs via Sirt1/HIF-1αsignal pathway. This study provides new evidence to clarify the protective mechanisms of Sirt1 in diabetic nephropathy.

[Summary] The aim of this study was to detect the levels of serum miR-130b expression in patients with type 2 diabetes mellitus and to analyze their correlation with diabetic renal damage. 243 patients with type 2 diabetes mellitus were divided into three groups according to urinary albumin/creatinine ratio ( UACR ): normoalbuminuria group (UACR<30 mg/g, n=103), microalbuminuria group (UACR 30-300 mg/g, n=86), and macroalbuminuria group(UACR>300 mg/g, n=54). The levels of serum miR-130b were validated by realtime polymerase chain reaction. Serum transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α(TNF-α) were determined by enzyme-linked immunosorbent assay ( ELISA) in all patients and 59 healthy volunteers. Compared with control group, the level of serum miR-130b in the type 2 diabetes mellitus group were significantly decreased, gradually with the increases of UACR. The level of serum miR-130b was inversely correlated with blood urea nitrogen ( r=-0. 295, P<0.05), serum creatinine(r=-0. 316, P<0. 05), UACR(r=-0. 463, P<0. 05), but positively related to the estimated glomerular filtration rate(r=0. 367, P<0. 01). The level of serum miR-130b was also negatively correlated to homeostasis model assessment for insulin resistance, triglyceride, low density lipoprotein-cholesterol, TNF-α, and TGF-β1 (r=-0. 257,-0. 345,-0. 242,-0. 562,-0. 622, all P<0. 01). The present study indicates that serum miR-130b might be a potential new biomarker for early diagnosis of diabetic nephropathy. Serum miR-130b might be involved in the pathogenesis of diabetic nephropathy.

Bronchi ; Child, Preschool ; Diagnostic Errors ; Foreign Bodies ; diagnosis ; Humans ; Lung Diseases ; congenital ; diagnosis ; Male

OBJECTIVETo study the expression of the receptor for advanced glycation end products (RAGE) and the inhibitory effect of advanced glycation end products (AGEs) on testosterone production in rat Leydig cells.

METHODSRat Leydig cells were primarily cultured and the expression of RAGE in the Leydig cells was detected by RT-PCR and immunofluorescence staining. The Leydig cells were treated with AGEs at the concentrations of 25, 50, 100 and 200 microg/ml, respectively, and the testosterone content was determined by ELISA.

RESULTSRT-PCR and immunofluorescence staining exhibited the expression of RAGE in the rat Leydig cells. AGEs remarkably suppressed hCG-induced testosterone production in the Leydig cells in a concentration-dependent manner in the 50, 100 and 200 microg/ml groups as compared with the control (P < 0.01).

CONCLUSIONRAGE exists in rat Leydig cells and AGEs can significantly inhibit the secretion of testosterone in primarily cultured rat Leydig cells.

Animals ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Glycation End Products, Advanced ; pharmacology ; Leydig Cells ; metabolism ; radiation effects ; Male ; Rats ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Testosterone ; biosynthesis

Objective To observe the effect of different intra-abdominal pressure and different time points on hemodynamics,ent-tidal CO_2(P_(ET)CO_2) and airway pressure(Paw) during the procedure of gynecological laparoscopic operations.Methods 60 cases undergoing gynecological laparoscopic operations were randomly divided into two groups:the intra-abdominal pressure was 1.3kPa in groupⅠ(30 cases) and 1.9kPa in groupⅡ(30 cases).ASAⅠgrade.In both groups,systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP), heart rates(HR).S-T.Paw and P_(ET)CO_2 were monitored and recorded before anesthesia(T_0),shortly after intubation (T_1),pre-pneumoperitoneum (T_2),5min after pneumoperitoneum (supine position) (T_3) and 5min (T_4),10min (T_5),20min(T_6),30min (T_7) after trendelenbury position (head down 200) and 5rain after deflation (T_8).Results In both groups SBP,DBP,MAP at time point T_3,T_4,T_5 were increased significantly compared with those of T_0 (P0.05),but there was significant difference in Paw and P_(ET)CO_2 in different time points within the same group and between the same time point in different groups after pneumoperitoneum(P

Objective To evaluate the effects of different doses of lidocaine on suppressing fentanyl-induced cough and determine a safe suppressing dose.Methods Two hundred patients undergoing general anesthesia were randomized to four groups evenly.The following medications were given within ten seconds:normal saline 10ml (groupⅠ,control group),lidocaine 1 mg/kg (groupⅡ),lidoeaine 1.5 mg/kg(groupⅢ),lidocaine 2mg/kg (groupⅣ).Toxic symptoms of lidocaine were recorded within lmin after the administration of lidocaine,then fentanyl 3?g/ kg was given intravenously within 5 seconds.Cough incidence and cough grade were recorded within 2rain after the administration of fentanyl.Systolic blood pressure (SBP),diastolic blood pressure (DBP),heart rates (HR),and satu- ration of pulse oximeter(SpO2) were recorded during different time points of induction,all recorded data were anal- ysed by the statistical software,P value

ObjectiveTo investigate the relation of the human cytomegalovirus pp67-mRNA with　the active infection in renal transplant recipients and the role in the direction for antiviral therapy.Methods　Total 128 samples were collected from peripheral blood treated with EDTA of 32 recipients at the 3rd week　or the 7th week after transplantation.IFA was used to detect CMV pp65 antigen,and NASBA was used to　detect pp67 mRNA assay.Compared with CMV-Ag,the recipients were followed up to observe the change of　pp67 in the cases of the active infection and the CMV disease.ResultsCompared with the proportion between two groups,44 samples out of 128 samples showed CMV-Ag pp65 positive,while pp67-mRNA were　positive in 21 samples.8 patients had been found positive CMV-Ag pp65 and pp67-mRNA; 12 recipients　were clinically diagnosed with HCMV disease.In the early stage of the HCMV infection,the sensitivity and　specificity of the CMV-Ag pp65 ( 91.7％,50.0％ ) was higher than that of pp67-mRNA ( 66.7％,95.0％ ).During the periods of symptoms appeared and the late stage of clinical treatment,the specificity　of pp67-mRNA was higher than that of CMV-Ag pp65,while the sensitivity sit on the contrary.And in the　antiviral therapy course,the indicator of antiviral therapy pp67 turned negative more quickly than the CMVAg,the therapy course could be reduced.ConclusionsBoth of CMV-Ag pp65 and of pp67-mRNA have　clinical significance.Testing for CMV-Ag pp65 is suitable for detecting HCMV active infection at the early　stage,which was important for in time anti-virus treatment in the clinical settings.The test for pp67-mRNA　is a quick method to accquire the accurate results; therefore,it can be used as the reference criteria for the　clinical anti-virus treatment.