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

[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.

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.

Objective To investigate the diagnostic value of the immediate early antigen(IE) mRNA by nucleic acid sequence-based amplification(NASBA) in peripheral blood cytomegalovirus (CMV) infection,and to establish and promote the diagnosis method for CMV.Methods Five to seven ml blood was taken from 32 patients at 3 week and 7 week after renal transplantation to detect serum cytomegalovirus antigen and antibody expression by NASBA,Real time-PCR and enzyme-linked immunosorbent assay (ELISA) sensitivity and specificity were compared.Results The results of CMV detection in 32 renal transplanted patients respectively showed that the positive rate of peripheral blood IE-mRNA by NASBA was 45.8％ (15/32) ;The positive rate of HCMV-DNA in blood by Real time-PCR was 45.8％ (15/32).Using ELISA,the positive rate of HCMV-(IgG +IgM) was 37.5％ (14/32).IE-mRNA and HCMV-DNA had higher sensitivity and specificity and lower false positive rate than HCMV-(IgG +IgM).The positive rates of IE-mRNA by NASBA,Real time-PCR and ELISA were 92.8％,71.5％ and 42.8％ respectively in the 14 cases.Conclusion The nucleic acid amplification method (NASBA based sequence) and Real time-PCR are sensitive,rapid diagnosis methods of HCMV infection,with higher sensitivity and specificity and lower false positive rate than traditional ELISA.And NASBA detection of IE-mRNA has good value for auxiliary clinical diagnosis.

Objective To investigate the potential role of miR-34a on breast cancer recurrence and prognosis.Methods In this study,88 breast cancer patients underwent mastectomy with detailed clinical follow-up information.Extracting RNA from the formalin-fixed paraffin embedded samples,miR-34a levels were quantified by quantitative real-time polymerase chain reaction (qRT-PCR).miR-34a levels among clinico-pathological variables were accessed by Mann Whitney-U test.RFS and OS survival curves were derived from Kaplan-Meier estimates and the curves were compared by Log-rank tests.All statistical tests were two-sided.Results Significantly lower miR-34a level was found in tumor tissue compared to paired normal tissue (P =0.000).A potential relationship between miR-34a levels and existing clinico-pathological parameters of breast cancer,such as menstrual status,tumor size,nodal involvement,stage of disease,hormone receptor status,HER2 status,or tumor subtype was investigated.No statistically significant difference were identified for these features (P ＞ 0.05).miR-34a level was significant lower among G3 group than G1 + 2 group (P =0.024).Down-regulated miR-34a level was observed in breast cancer with later relapse compared to patients without relapse (P =0.008).When considering 2-△Ct =0.117 (median level)as cut-off value,patients with miR-34a up-regulation showed a positive association towards a longer survival,either RFS(P=0.026,Log-rank test) or OS(P =0.019,Log-rank test).Conclusions miR-34a,as a tumor suppressor,promotes differentiation and contributes to relapse when down-regulated.miR-34a has the potential as prognostic factor for breast cancer.

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.

Objective To study the diagnosis and treatment of synchronous gastric cancer and gastric stromal tumor in 18 cases. Methods Clinical data of 18 cases of synchronous occurrence of gastric cancer and gastric stromal tumor from January 1996 to December 2009 were analyzed retrospectively.Results Clinical features of all cases were atypical. There was 1 case diagnosed preoperatively, 3 cases diagnosed intraoperatively and 14 cases diagnosed postoperatively. The mean size of gastric cancer and gastric stromal tumor was (3.3±2.3) cm and (0.9 ±0.5) cm respectively. There were 16 cases of gastric stromal tumor in low risk of malignance and 2 cases in moderate risk of malignance. All cases were operated without complications and the 1-year, 3-year and 5-year overall survival rate was 88.2%, 63.2% and 36. 1% respectively. Conclusions Clinical features of synchronous occurrence of gastric cancer and gastric stromal tumor are atypical, in this series most gastric stromal tumors are in early stage and of low risk of malignance. The prognosis of patients with synchronous occurrence of gastric cancer and gastric stromal tumor mainly depends on gastric cancer.

Objective To improve the understanding of the characteristics of obstructive sleep apnea-hypopnea syndrome (OSAHS) in the elderly patients, and to improve the diagnosis and treatment level. Methods Monitoring results of polysomnography (PSG) from 110 elderly OSAHS patients were analyzed retrospectively. The general conditions, sleep architecture, apnea and hypopnea events, oxygen reduction as well as possible correlations between various indicators were analyzed using SPSS18.0 statistical software. Results The median rapid eye movement (REM) and non-REM (NREM) sleep time of elderly patients with OSAHS accounted for 2. 17% and 76.73%,respectively. The median arousal index was 45.6 times/h. The longest time of sleep apnea was (51.94±22.06) s, the median of average sleep apnea time was 22.50 s, the longest time of hypopnea was (47.06±12.52) s and the average hypopnca time was (21.50±4.63) s. The median respiratory disturbance index (RDI) of all patients was 21.50, the patients with RDI between 5 and 20 accounted for 46.40%, with RDI between 20 and 40 accounted for 31.80% and with RDI over 40 accounted for 21.8%. The average oxygen saturation accounted for (93.45% ± 2.81%), the lowest oxygen saturation accounted for (76.3%± 10. 5%) and the median oxygen desaturation index was 31.6;times/h. BMI was negatively correlated with lowest oxygen saturation (r=-0. 378, P＜0.01) and average oxygen saturation ( r = - 0. 355, P ＜ 0. 01 ), while was positively correlated with oxygen desaturation index (r=0. 338, P＜0. 01 ). The lowest oxygen saturation was negatively correlated with the longest time of obstructive apnea (r= -0. 47, P＜0. 01 ), the average time of obstructive apnea (r=-0.316, P＜0.01), the longest time of hypopnea (r=-0.293, P＜0.01) and the average time of hypopnea (r=-0. 277, P＜0.01). The median time intervals of oxygen desaturation during supine, left side and right side position were 2.36 min, 11.54 min and 12.45 min,respectively. The median time intervals of oxygen desaturation during left side and right side position were both longer than that of supine position (Z= -6.12 and -7. 10 respectively, both P＜0.01).Conclusions Elderly patients with OSAHS manifest obvious disorder of sleep structural and sleep fragmentation. According to RDI, the majority of the patients are classified as mild to moderate in severity. However, elderly patients with OSAHS are severe regarding to hypoxia relatively. The severity of hypoxia is related with BMI and the lasting time of sleep-disordered breathing events, and hypoxia are less severe when sleeping on left side or on right side.