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.

[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.

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.

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 investigate the clinical value of double contrast-enhanced ultrasonography (DCUS) for the diagnosis of gastric cancer.Methods A retrospective analysis was performed to review the DCUS data of 26 patients which were diagnosed as gastric cancer by pathology in the third affiliated hospital of Kunming Medical University from October 2014 to July 2015.The analysis results were compared with postoperative pathology to get accuracy rates.Results The located accuracy,qualitative accuracy and accuracy at T phase of DUCS was 100％ (26/26),100％ (26/26) and 88.5％ (23/26),respectively.Compared with color doppler flow imaging (CDFI),the qualitative accuracy of DUCS was much higher (P ＜ 0.05).The accuracy of DUCS at T phase was higher than that of CDFI with no statistical significance (P ＞ 0.05) Conclusion DUCS has an important application value in the diagnosis of gastric cancer.

Objective To analyze the etiologies,clinical characteristics and prognostic factors of patients with acute renal failure(ARF)admitted to the hospital at high altitude.Method This retrospective study included clinical data of patients with acute renal failure in the General Hospital of Tibet Military Command from May 2001 to April,2006.Results There were 85 male patients and 63 female patients with mean age(42.4?18.1)years old.Among 148 patients with acquired ARF,52.7% was iatrogenic or nosoeomal origin, demonstrating a trend of increasing.The ARF included pre-renal(n=48,32.4%),renal parenchymal(n= 90,60.8%)and post-renal(n=10,6.8%)in origin.Acute high altitude sickness(n=20)was the major causes of pre-renal ARF.Renal parenchymal ARF could be classified into glomerular vascular lesions(n=24), acute tubular necrosis(n=53),acute interstitial nephritides(n=12),and contusion of unitesticle(n=1).of 90 cases of renal parenchymal ARF,39 patients(43.3%)were induced by medicines.Lithiasis was the major causes of post-renal ARF.The mortality of ARF in our study was 42.6%.The mortality of patients contracted ARF in hospital was much higher than that of patients community ARF in community(55.1 vs 23.6%;P=0.01). There was no significant differences of the mortality between the patients with and without dialysis treatment. Univariate analysis showed that prognosis was correlated with age,the presence of hematuria and oliguria or anuria Hb,and the number of organ system failures.The logistic regression showed that age,Hb and the number of organ system dysfunction were the predictors of mortality.Conlusions The major causes of ARF at high altitude were acute high altitude sickness and the use of medicines with nephrotoxicity.The morbility and mortality of nosocomisl ARF increased significantly.Prevention of MODS is a key management to decrease mortality in severe ARF.

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