Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.
Animals ; Channelopathies ; physiopathology ; Hippocampus ; drug effects ; Neurons ; drug effects ; Neurotoxins ; pharmacology ; Venoms ; chemistry ; Voltage-Gated Sodium Channel Blockers ; pharmacology

Objective To build a clinical key disciplines evaluation index system for county level hospitals in Chengdu city.Methods Literature meta analysis, focus group discussion, expert consultation method, boundary value method, brainstorming and hierarchy analysis method were comprehensively used.Results The clinical key disciplines evaluation index system for county level hospitals in Chengdu city comprises 5 level-1 indexes,1 6 level-2 indexes,47 level-3 indexes.Among the level-1 indexes,service capacity,medical quality,technical personnel,scientific research and education, and foundation of specialty was 0.474 6,0.202 7,0.148 2,0.097 7,0.076 8 respectively.Conclusion The clinical key disciplines evaluation index system for county level hospitals in Chengdu city is scientific, guiding and practical,which can be used to evaluate the status of the clinical key disciplines for county level hospitals in Chengdu city.

Objective To investigate the safety and short-term effectiveness of the hybrid operation for the treatment of intracranial complex ruptured aneurysms.Methods From December 2014 to March 2017,14 consecutive patients with complex ruptured aneurysm treated with hybrid operation at the Department of Neurosurgery,Nanfang Hospital,Southern Medical University were enrolled retrospectively,including 13 with acute spontaneous aneurismal subarachnoid hemorrhage and 1 with hemorrhage in the recurrent aneurysm embolization.Twelve aneurysms were treated with shape clipping.Digital subtraction angiography (DSA) was used to evaluate the clipping effect of aneurysms.Two patients with aneurysm were treated with extracranial-intracranial (EC-IC) bypass and aneurysm trapping.Endovascular balloon occlusion for trapping aneurysms was performed after DSA evaluation of the patency of bridge vessel.Results Of the 14 patients,11 were treated with emergency hybrid operation after angiography,2 were treated with elective surgery,and 1 with emergency surgery for rescue because of bleeding during embolization.DSA revealed that the aneurysm clips in 3 of 12 patients needed to be adjusted,including 2 parent artery stenosis and 1 with incomplete clipping.After adjustment,the clipping was satisfactory.In intracranial and extracranial bypass surgery,angiography revealed that the blood vessels were patent.Trapping of the aneurysms was performed in the one-stage operation.One patient discharged voluntarily after procedure because of serious vasospasm.Onepatient had perfusion pressure breakthrough after surgery and received hematoma evacuation and decompression.The Glasgow outcome scale (GOS) score was 3 at discharge.Other patients had no new neurological dysfunction after operation.Thirteen patients were followed up for 3-24 months after operation.There were no new neurological dysfunction,including GOS 5 in 8 cases and 4 in 5 cases.Six patients underwent DSA examination,in 4 of them the aneurysm clipping did not show aneurysm recurrence,and the parent arteries were patent.Two patients treated with vascular bypass.There were no recurrence of aneurysms,and the parent arteries and anastomotic vessels were patent.Conclusion After preliminary observation,using hybrid operation for the treatment of complicated intracranial ruptured aneurysms was safe and effective.

AIM To study the chemical constituents from Chloranthus japonicus Sieb..METHODS The ethyl acetate fraction of 95％ ethanol extract from C.japonicus was isolated and purified by silica,Sephadex LH-20,ODS and PHPLC column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Ten compounds were isolated and identified as p-hydroxyphenethyl (1),diisooctanephthalate (2),diisobutylphthalat (3),umbelliferone (4),ursolic acid (5),7α-hydroxysitosterol (6),chloranthalactone E (7),chloranthalactone B (8),apigenin (9),3-Sitosterol (10).CONCLUSION Compounds 1-3,6 are isolated from genus Chloranthus for the first time,compounds 4,5,9 are first isolated from this plant.

OBJECTIVETo sum up our experience in percutaneous dilatational tracheostomy (PDT) in ICU patient with severe brain injury.

METHODSBetween November 2011 and April 2014, PDTs were performed on 32 severe brain injury patients in ICU by a team of physicians and intensivists. The success rate, efficacy, safety, and complications including stomal infection and bleeding, paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, as well as clinically significant tracheal stenosis were carefully monitored and recorded respectively.

RESULTSThe operations took 4-15 minutes (mean 9.1 minutes ± 4.2 minutes). Totally 4 cases suffered from complications in the operations: 3 cases of stomal bleeding, and 1 case of intratracheal bloody secretion, but none required intervention. Paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, or clinically significant tracheal stenosis were not found in PDT patients. There was no procedure-related death occurring during or after PDT.

CONCLUSIONOur study demonstrats that PDT is a safe, highly effective, and minimally invasive procedure. The appropriate sedation and airway management perioperatively help to reduce complication rates. PDT should be performed or supervised by a team of physicians with extensive experience in this procedure, and also an intensivist with experience in difficult airway management.

Brain Injuries ; therapy ; Critical Care ; Humans ; Operative Time ; Postoperative Complications ; Tracheostomy ; methods ; Treatment Outcome

Objectives To evaluate the expression profile of myoD microRNA-29 (miR-29) family in L6 myoblast differentiated to myotube or L6 myotube treated by glucose and insulin, and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.
Methods The expression of myoD and miR-29 family was detected by using real-time PCR and Western blot analysis. The potential promoter and transcription factors binding sites of miR-29 clusters were predicted by Promoter scan and transcriptional factor search. The promoter sequence of miR-29b1-a and miR-29b2-c cluster was cloned into a luciferase reporter plasmid and the regulatory effect of myoD was analyzed by using dual luciferase reporter assay. Electrophoretic mobility shift assay was further conducted to indicate the binding of myoD on specific sequence. Moreover, overexpression of myoD was achieved by a recombinant adenovirus system (Ad-myoD). L6 cells were infected with Ad-myoD and real-time PCR was conducted to analyze the expression of miR-29b and miR-29c.
Results The expression levels of myoD, miR-29a, miR-29b, and miR-29c were increased in L6 myoblast differentiated to myotube. The expression of myoD, miR-29b, and miR-29c was up-regulated in L6 myotube treated with glucose and insulin, but miR-29a depicted no significant change. Dual luciferase reporter gene assay showed that myoD functioned as a positive regulator of miR-29b2-c expression and myoD could bind to the specific sequence located at the promoter region of miR-29b2-c cluster. Enforced expression of myoD led to a marked increase of miR-29b and miR-29c levels in L6 cells.
Conclusion MyoD might act as a crucial regulator of myogenesis and glucose metabolism in muscle through regulating the expression of miR-29b2-c.

In our previous study, normal and fertile mice were successful produced from oocytes following intracytoplasmic sperm injection (ICSI). In the present study, the possibility of producing transgenic embryos and offspring with this procedure was evaluated. After freezing-thawed once using HEPES-CZB medium without cryoprotectants, the cauda sperm from KM fertile male were exposed to the circular or linear pEGFP-N1 DNA for 1 min and then co-injected into metaphase II oocytes of B6D2F1 strain. When the zygotes with two pronuclei were cultured in CZB medium to day 3.5, 39.1% (9/23) of them, derived from oocytes co-injected with sperm head and pEGFP-N1 plasmid DNA, were expressed GFP protein. After transfer of the ICSI embryos with two pronuclei from co-injection of sperm head and foreign DNA, seven recipients delivered 30 pups (23.8%, 30/126). Southern blot results revealed that three of sixteen offspring integrated with GFP and neomycin genes together (18.8 %). Interestingly, all of them were produced from oocytes co-injected sperm head and linear DNA (33.3%, 3/9), while none of seven ICSI offspring integrated either GFP or neomycin gene in the group of co-injection of sperm head and circular plasmid DNA. These results indicated that the high efficiency of transgenic mouse could be produced by ICSI. It may be shown that linear DNA is more easily to integrate into host genome than circular DNA when ICSI was used to produce transgenic animals.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; genetics ; Sperm Injections, Intracytoplasmic ; methods

Objective To investigate the constituents of water and ethanol extracts from the stems and leaves ofAucklandia lappa and their effect on gastric emptying and intestinal propulsion of gastrointestinal normal,hyperthyroidism and inhibited mice.Methods The water,ethanol and aether petrolei extracts from stems and leaves of A.lappa were prepared,and the chemical constituents of the stems and leaves were identified by chemical reaction.The hyperthyroidism state was induced by neostigmine and inhibiting state was induced by atropine.Mice were ig administered with water and ethanol extracts (0.5 g/kg),with the improved phenol red method to determine gastric emptying and intestinal propulsion in gastrointestinal normal,hyperthyroidism and inhibited mice.Results Both water and ethanol extracts significantly improved intestinal propulsion in normal mice (P ＜ 0.05 and 0.01),while significantly decreased the intestinal propulsion in hyperthyroidism mice (P ＜ 0.05) and ethanol extract showed a stronger decreasing effect than that of water extract.The inhibitory effect of atropine on intestinal propulsion was intensified by these two extracts (P ＜ 0.05).The restrained gastric emptying of normal,hyperthyroidism and inhibited mice was also observed.Chemical composition analysis indicated that many kinds of chemical components including protein,sugar,essential oil,flavonoids,lactones,alkaloids,saponins and tannins existed in the leaves and stems of A.lappa.Conclusion The leaves and stems of A.lappa could promote the intestinal propulsion of normal mice and restrain the intestinal propulsion of hyperthyroidism and inhibited mice while inhibit the gastric emptying in any condition tested,and its promoting effect on the gut may be related to the M cholinergic receptor.

OBJECTIVE:To evaluate the efficacy and safety of cerebrolysin in adjuvant treatmenut of acute cerebral infarction systematically,and to provide evidence-based reference in clinic.METHODS:Retrieved from SCI,Cochrane Library,EMBase,PubMed,CJFD,VIP and Wanfang Database,RCTs about cerebrolysin combined with routine plan (trial group) vs.routine plan alone or combined with placebo (control group) in adjuvant treatment of acute cerebral infarction were collected.After data extraction and quality evaluation by using Cochrane systematic review manual 5.1.0,Meta-analysis was conducted by using Rev Man 5.2 statistical software.RESULTS:A total of 20 RCTs were included,involving 3 313 patients.Meta-analysis showed that NIHSS score [MD=-1.77,95％CI(-2.33,-1.21),P＜0.001],response rate [OR=2.85,95％CI(1.75,4.63),P＜0.001] and Barthel index (BI) score [MD =7.30,95 ％ CI (3.48,11.13),P＜ 0.001] in trial group were significantly higher than control group,with statistical significance.There was no statistical significance in disability rate [OR=0.46,95％ CI(0.20,1.03),P=0.06],mortality [OR=0.79,95％ CI (0.52,1.19),P=0.25],the incidence of ADR [OR=1.04,95％ CI (0.85,1.27),P=0.72] or the incidence of severe ADR [OR=0.01,95％CI(-0.02,0.04),P=0.51] between 2 groups.CONCLUSIONS:Cerebrolysin is good for adjanctive therapy of acute cerebral infarction,can significantly improve neurologic impairment and life quality and dosen't increase the incidence of ADR.

OBJECTIVETo investigate the inhibitory effect of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5) on xenografted human prostatic cancer in nude mice and its action mechanism.

METHODSWe established a model of xenografted prostatic cancer by inoculating PC-3 cells subcutaneously into nude mice, and 3 weeks later injected CMTM5 adenovirus locally into the tumor followed by daily observation of the tumor volume and body weight of the experimental animals. All the rats were killed 2 weeks after CMTM5 injection and the tumor tissue harvested for detection of the inhibitory effect of CMTM5 on the expressions of VEGF and NF-kappaB proteins by immunohistochemistry.

RESULTSThe tumor volume was significantly smaller and body weight of the CMTM5-treated mice were (573.39 +/- 175.24) mm3 and (0.55 +/- 0.11) g, respectively, significantly decreased as compared with those of the controls ([1482.50 +/- 327.86] mm3 and [1.31 +/- 0.29] g) (P = 0.03 and P = 0.027). Immunohistochemistry showed that the expressions of VEGF and NF-kappaB were obviously down-regulated in the CMTM5 group in comparison with the control group.

CONCLUSIONCMTM5 suppresses the growth of prostate cancer by down-regulating the expressions of VEGF and NF-kappaB.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Chemokines ; genetics ; pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; MARVEL Domain-Containing Proteins ; genetics ; pharmacology ; Male ; Mice ; Mice, Nude ; NF-kappa B ; metabolism ; Prostatic Neoplasms ; metabolism ; Tumor Suppressor Proteins ; genetics ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays