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

[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.

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.

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 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 identify the variation in the Env region of SHIV-XJ02170 during passaging in Chinese origin Rhesus Macaques.Methods Fragments of the SHIV-XJ02170 gp160 and gp120 gene were amplified by PCR and RT-PCR separately from the blood samples of SHIV-XJ02170 infected animals at the peak viral load time point.Purified RT-PCR product was ligated into T easy vector and transformed into JM109 competent cells,18 clones were selected by PCR method and sequenced by ABI 3730DNA sequencers.The gene distances(divergence,diversity)were calculated using DISTANCE.Results In all,the SHTV-XJ02170 gp120 gene evolved forward along the virus passaging.It could be found that viral divergence from the founder strain serially enhanced during in vivo passaging,but in the early phase of each passage,SHIV-XJ02170 gp120 gene evolved toward ancestral state upon transmission to a new host.All of the SHIV-XJ02170 strains had V3 loop central motif(GPGQ)and were predicted to be using CCR5 on the basis of the critical amino acids within V3 loop.Conclusion There was significant increase in the genetic distance during serial passaging,and SHIV-XJ02170 gp120 gene evolved forward along passaging.This could partly explain why the virus infectivity was enhanced during in vivo passaging.

Objective To analyze the virologic and immunologic properties during SHIV-XJ02170passage in vivo and construct the clade C SHIV/Chinese origin Rhesus macaques AIDS model . Methods SHIV-XJ02170 cell-free virus tranfected in 293T was adapted by serial passage in nine Chinese-origin Rhesus macaques. CD4/CD8 ratio was detected by flow cytometry to analyze the changes in viral pathogenicity. Real-time RT-PCR and IFN-γsecreting ELISPOT methods were used to analyze changes in characteristics of virology and immunology. Results During in vivo passage, CD4/CD8 ratio did not deeply decline. However,the peak and setpoint viral load in the line 3 show a continuous upward trend. The strong humoral and cellular immune responses were induced after SHIV-XJ02170 infection. Meanwhile, there was significant positive correlation between the viral load and binding antibody titer. Conclusion There were no pathogenic viral strains, and upward trend in virulence of SHIV-XJ02170 was found during in vivo passaging. SHIVXJ02170/Chinese origin Rhesus macaques model will play an important role in effect evaluation of candidate AIDS vaccines in China.

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.