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

Eyelid reconstruction is complex and challenging since it is not only for structural and functional restoration, but also for an acceptable aesthetic result. In full thickness eyelid injuries, it will involve both anterior and posterior lamella. Therefore, when reconstructing the defect, it requires at least two layers; one will be a flap with blood supply, and the other can be a free graft. In this case, a rotational advancement cheek flap and composite graft were used to reconstruct the lower eyelid.

Objective To investigate the role of IL-6/STAT3 signaling in Th17/Tr imbalance of Kawasaki disease(KD). Methods Forty-eight children with KD and eighteen age-matched healthy children were consented to participate in this study. Protein concentration of IL-6 in plasma was measured by ELISA. Transcriptional levels of IL-17A, IL-17F, RORγt, Foxp3, SOCS1 and SOCS3 were assessed by real-time PCR. The proportion of CD4+CD25+Foxp3+ regulatory T(Tr) cells and mean fluorescence intensity(MFI) for phosphorylated-STAT3(pSTAT3) protein in CD4+ T cells was analyzed by flow cytometry. A quantitative methylation specific PCR based on SYBR Green was used to evaluate methylation status of CpG islands in SOCS1 exon2, three potential bind sites for STAT3 in 5'-untraslated region(5'-UTR) of SOCS3 in CD4+ T cells. Results (1)Compared with healthy volunteers, plasma IL-6 concentration and MFI for pSTAT3 in CD4+ T cells were elevated significantly during acute phase of KD[IL-6:(54.02±20.58) pg/ml vs (8.72±2.06) pg/ml, P<0.05;pSTAT3 MFI:(55.41±15.08) vs (9.35±3.76), P<0.05], and the two items in KD patients with coronary artery lesion (KD-CAL+) were found to be higher than those in KD patients without coronary artery lesion (KD-CAL-)[IL-6:(84.76±29.35) pg/ml vs (38.65±13.76) pg/ml, P<0.05;pSTAT3 MFI:(72.36±16.81) vs (46.93±13.57), P<0.05]. (2)Transcription levels of IL-17A, IL-17F and RORγt in patients with KD were significantly elevated (P<0.05) while the proportion of CD4+CD25+Foxp3+ Treg and expression levels of Foxp3 were detected to be lower than those in normal controls (P<0.05). The mRNA levels of IL-17A, IL-17F and RORγt in KD-CAL+ group were higher than those in KD-CAL- group(P<0.05), as well as expression level of Foxp3 were found to be lower in KD-CAL+ group(P<0.05). (3)The mRNA levels of SOCS1 and SOCS3 in CD4+ T cells increased significantly during acute phase of KD(P<0.05), while the two items in KD-CAL+ group were lower than those in KD-CAL- group(P<0.05). Furthermore, CpG islands in SOCS1 exon2 and the third potential bind site for STAT3 in SOCS3 5'-UTR were hypomethylated in acute KD, while those in healthy controls were fully demethylated(P<0.05). Demethylation levels of SOCS1 exon2 and the third potential bind site for STAT3 in SOCS3 5'-UTR in KD-CAL+ group were lower than those in KD-CAL- group(P<0.05). CpG islands in the other two bind sites for STAT3 in SOCS3 5'-UTR were fully demethylated among all the groups(P>0.05). ConclusionAberrant activation of IL-6/STAT3 signaling caused by hypomethylation of SOCS1 and SOCS3 might be one contributing factor to unbalance of Th17/Tr in KD.

Objective To evaluate a minimally invasive procedure for intertrochanteric fracture treatment in elderly patients. Methods Total 46 elderly patients with intertrochanteric fracture were treated with a minimally invasive procedure from September 2008 to February 2010. The fractures were fixed with multiple K-wires combined with skeletal traction through supracondyle of femur. All procedures were undertaken under local anesthesia. Results All the patients were followed up for 8.8-months in average, and 42 patients recovered with independent walking, and the good rates was 91.3%, without severe complications in this group. Conclusions Minimally invasive procedure including fixation with multiple K-wires combined with traction through femoral supracondyle, is a safe and effective treatment for intertrochanteric fracture in elderly patients, avoiding high risks of intra-and post-operative complications.

Objective To evaluate hepatectomy for liver metastasis in patients of gastric carcinoma.Methods Clinical data of 32 gastric cancer cases undergoing hepatectomy for hepatic metastatic tumor were reviewed retrospectively from 2006 to 2012.16 cases underwent radical gastrectomy and synchronous hepatectomy for liver metastasis,the remaining 16 cases underwent radical resection of gastric cancer and liver resection heterochronously.The relationship between prognosis and clinicopathology was analyzed.Results The overall survival rates were 84％,50％ and 37％ in 1 year,3 years and 5 years.The median survival time was 32 months.Gastric cancer invasion depth,intravascular tumor thrombi,lymphatic metastasis and intraoperative blood transfusion was related to poor prognosis by single factor analysis,while gastric serosal invasion,tumor thrombus and liver metastasis tumor ＞ 5 cm related to poor prognosis by multiple factors analysis.Conclusions Gastric cancer patients with liver metastasis who underwent hepatic resection can achieve good prognosis if hepatic metastatic tumor ＜ 5cm or the primary gastric cancer does not invade the serosa and without tumor thrombus.

Objective To explore the effectiveness of early enteral nutrition (EN) support and growth hormone (GH) treatment in critically ill patients.Methods Seventy critically ill patients were randomly divided into early EN support group and early EN support plus GH treatment group.The nutrition intakes were isonitrogenic and isocalorie in these two groups.Body weight,blood biochemistry,nutritional statues,and lactulose/mannitol levels were measured or analyzed before and after nutrition support.Immunologic functions were analyzed after ten days.Nitrogen balance was measured daily.Results The changes of body weight,albumin level,and transferrin level were more obvious in the EN + GH group than those in the EN group without significant difference (P ＞0.05).The changes of prealbumin and fibronectin in the EN + GH group were significantly higher than those in the EN group (P ＜ 0.05).The level of IgA in the EN + GH group was significantly lower than that in the EN group,while the levels of CD4 and NK in the EN + GH group was significandy higher than those in the EN group (P ＜0.05).The gut barrier function in the EN + GH group was superior to that in the EN group during nutrition support (P ＜0.05).Nitrogen balance was positive in the EN + GH group and negative in the EN group (P ＜ 0.05).Conclusions Early EN can improve the nutritional status and reduce complications in critically ill patients.GH treatment may strengthen the immune function and remarkably decrease the disability and mortality in critically ill patients.

Objective To evaluate the effectiveness of several methods in eliminating Mycoplasma contamination in cell culture of human hepatoma-derived cell line C3A. Methods PCR was performed to detect the Mycoplasmas contamination in cell cultures. The contaminated samples were treated by ciprofloxa-cin, heating, Plasmocure or co-culturing with macrophages. Transmission electron microscope ( TEM) and Q-PCR were used to comparatively analyze the cell morphology and gene expression before and after Plas-mocure treatment. Results Plasmocure succeeded in eliminating Mycoplasma contamination, while cipro-floxacin showed temporary efficacy. Heating and co-culturing with macrophages failed to eliminate Mycoplas-ma contamination. No Mycoplasma contamination in the Plasmocure-treated group was observed under TEM and the expression of ALB, TF and CYP3A4 genes were higher than the genes expressed in the contaminated group (P<0. 01). Conclusion Plasmocure treatment was effective in eliminating Mycoplasma contamina-tion in cell culture. Moreover, the cell morphology and gene expression in Plasmocure-treated group were re-stored to normal.

Objective To describe a technique of closed reduction and percutaneous internal fixation for the treatment of displaced patellar fractures and evaluate the clinical results. Methods Fifteen cases (nine males and six females with mean age of 35.5 years, ranging from 24 to 65 years) with displaced patellar fractures were treated with closed reduction (or an arthroscopic-assisted reduction) and percutaneous cannulated screw fixation (or Kirschner wire tension band wiring technique) under guidance of fluoroscopy or C-arm X-ray tomography. Controlled passive range of motion exercises started on the first postoperative day. The mean follow-up was 28 months (24-35 months). Results All cases healed successfully with healing time of (1.2?2.2) months and mean Lysholm II score of 86.8 (79-96), except for one patient regained full knee range of motion. Compared with the contralateral side, a mean quadriceps atrophy of 0.8 cm was seen in unilateral cases based on Tandogan measurement. There was no implant failure or postoperative infection. Conclusions The technique of closed reduction and percutaneous internal fixation is appropriate for displaced, transverse, longitudinal or oblique patellar fractures and can facilitate early postoperative range of motion exercises and accelerate rehabilitation of the affected knee with few complications and minor incision without disturbing blood supply of the patella. But, this method is not suitable for severely comminuted fractures.

Objective To determine the advantages of laparoscopic cholecystectomy (LC) by establishing pneumoperitoneum under direct vision. Methods A 1cm incision was made just below the umbilicus; lifting and cutting out of the peritoneum at the line alba abdominis with direct vision; then a 10mm trocar was inserted into the pneumoperitoneum cavity.Results There were 107 patients underwent LC.Of them, 93 patients suffered from chronic cholecystitis with gallstone, 6 from acute cholecystitis with gallstone, and 8 from cystopolyps. Among them, 16 patients had previous abdominal operations. Two patients with atrophic cholecystitis converted to open cholecystectomy(OC) owing to the unclear bile duct anatomy. The average operation time was 45min. Postoperative complications included pulmonary infection in 3 patients, bile leakage in 1( due to the titanic clip falling off),but no bile duct injury or other severe complications occurred;and no mortality in this series. Conclusions Establishing pneumoperitoneum under direct vision has following advantages:rapid and safe,and favorable to avoid the severe trocar-related complications.

Objective To investigate the organ protective effects and the timing of continuous blood purification (CBP) in the treatment of severe sepsis. Methods A double-blind randomized controlled trial was conducted. Seventy-four patients with severe sepsis aged between 35 years and 80 years with acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) scores over 20 admitted to Department of Critical Care Medicine of the First Hospital of Wuhan from January 2013 to January 2015 were enrolled. They were divided into control group (n = 37) and treatment group (n = 37) by random number table method. All patients in these two groups received conventional therapy following the guidelines for management of severe sepsis in 2012. In addition the patients in treatment group received continuous veno-venous hemofiltration (CVVH). The critical score, liver and kidney function indexes, etc., levels of pro-inflammatory cytokines in plasma and ultra filtrate before and 24, 48, and 72 hours after treatment, and the clinical picture 2 weeks after treatment in two groups were observed. Results APACHE Ⅱ scores, multiple organ dysfunction syndrome (MODS) scores, Murray scores of acute lung injury, and systemic inflammatory response syndrome (SIRS) scores of the patients of the above two groups were gradually declined after the treatment. The levels of white blood cell count (WBC), procalcitonin (PCT), lactate (Lac), tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-8), and endotoxin gradually lowered. Levels of blood urea nitrogen (BUN), serum creatinine (SCr), alanine transaminase (ALT) and the oxygenation index (PaO2/FiO2) showed a tendency of lowering. There were statistically significant differences in scores of critical illness, WBC, PCT, Lac, pro-inflammatory cytokine, liver and kidney function indexes, etc. between treatment group and control group 48 hours after treatment (APACHE Ⅱ score: 15.5±4.7 vs. 20.3±5.3, MODS score: 4.6±1.4 vs. 7.3±2.2, Murray score: 1.4±0.5 vs. 1.7±0.6, SIRS score: 2.9±0.8 vs. 3.7±1.0, WBC (×109/L): 1.1±0.5 vs. 1.6±0.5, PCT (μg/L): 26.7±12.0 vs. 32.4±14.1, Lac (mmol/L): 7.6±2.2 vs. 9.3±2.8, TNF-α (μg/L): 96.3±17.4 vs. 153.4±24.2, IL-6 (μg/L): 146.8±20.6 vs. 213.8±29.2, IL-8 (μg/L): 287.1±43.6 vs. 354.5±56.2, endotoxin (kEU/L): 1.4±0.5 vs. 2.6±0.8, BUN (mmol/L): 8.7±3.6 vs. 18.5±6.4, SCr (μmol/L): 143±39 vs. 197±42, ALT (U/L): 141±27 vs. 183±34, PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 150.3±45.4 vs. 124.7±32.1, all P < 0.05], and the difference was significant up to 72 hours. In the treatment group, TNF-α, IL-6, IL-8, and endotoxin could be decreased in the filtrate 24 hours and 48 hours after treatment and they correlated with the lowering tendency of their plasma levels. Compared with the control group, CVVH based on conventional treatment of severe sepsis could significantly reduce the incidence of MODS (10.8% vs. 29.7%, χ2 = 4.423, P = 0.038) and mortality (5.4% vs. 13.5%, χ2 = 4.674, P = 0.032), and remarkably shortened the duration of mechanical ventilation (days: 3.1±0.6 vs. 5.3±1.7, t = 2.103, P = 0.045), and the length of intensive care unit (ICU) stay (days: 8.5±1.7 vs. 13.2±2.4, t = 2.245, P = 0.042). Conclusion Early CBP can decrease the level of pro-inflammatory cytokines, prevent MODS, and remarkably improve the prognosis of patients with severe sepsis.