As an outward,voltage-dependent potassium channel,M type channel is crucial in the regulation of neuronal excitability;it is modulated by a variety of factors in vivo and its dysfunction often results in neuronal system diseases.Great efforts have been made to elucidate the mechanism underlying M channel modulation since its discovery decades ago.It is generally accepted that the Phospholipase C(PLC) signaling pathway plays a significant role in the M channel modulation.This review highlights the relationship between PLC signaling pathway and M channel modulation,as well as some recent progresses in the research of this field.

Receptor tyrosine kinase(RTK),a membrane receptor superfamily with intrinsic protein tyrosine kinase activity,has many members and complicated signal transduction pathways.Activation of RTKs can trigger a series of signal transduction pathways and play essential roles in modulating cell growth,proliferation,differentiation and metabolism through influencing gene transcription and expression.Activation of RTK can also rapidly modulate some cellular functions including the modulation of ion channels.Potassium channels play a critical role in stabilization of membrane potential and regulation of cellular excitability.This review highlights the rapid modulation of potassium channels by RTKs and reviews the recent progress in related research.

AIM To evaluate bioavailability, biocompa- tibility and biodegradability of an injectable microsphere sustained release preparation of naltrexone(NTX) in 4 dogs. METHODS Pharmacokinetic data of NTX and remained NTX in microspheres in injection site were studied using high performance liquid chromatography(HPLC)-electrochemical detection with naloxone(NLX) as internal standard. Biocompatibility of the microspheres was assayed by histological examination. RESULTSPharmacokinetics of NTX after an intramuscular dose of 0.5 or 1.0 mg*kg-1 NTX indicated a plasma clearance range of 0.66 to 0.73 L*min-1 and a t1/2β range of 60.0 to 67.2 min. After a 1-week washout period without medication, NTX microspheres injection period about 4 weeks followed. After injection of 1.0 g of microspheres containing (296.5±2.1)mg of NTX, mean blood concentrations of NTX exceeded 1 μg*L-1 for 26-28 d, and cmax per dose (mg*kg-1) was only 1% of that after NTX dosing. It was estimated that approximately (93.0±4.1)% of the administered dose was absorbed after microspheres injection in 4 dogs. There were no serious adverse effects other than light tissue irritation. CONCLUSIONThis NTX microspheres preparation provides a safe, complete and sustained release of the drug for about one month.

Objective To establish normal reference indexes of aorta during gestation and cut-points for detection of fetuses with coarctation of aorta.Methods From long-axis views of the aortic arch,the internal diameter of the aortic root,ascending aorta,transverse aortic arch,aortic isthmus,descending aorta,anonyma,left common carotid artery,left subclavian artery were measured in 234 normal fetuses at different time ranging from 14 to 41 weeks during gestation.Reference values of each aortic segment were constructed by linear regression analysis.The ratio of each aortic segment to the ascending aorta were calculated.ResultsThe internal diameter in each aortic segments increased as pregnancy progressed (P<0.01).In the prenatal diagnosis of fetus with coarctation of the aorta,the ratio of the aortic isthmus to the ascending aorta and descending aorta to the ascending aorta were significantly lower than the normal fetuses(all P<0.01).Conclusions The ratio of the aortic isthmus to the ascending aorta and ratio of descending aorta to the ascending aorta detected by echocardiography may be helpful in the prenatal diagnosis of coarctation of aorta.

Pancreatic cancer is one malignancy with high aggressive and extremely poor prognosis,its incidence and mortality rates are increasing gradually in our country.Although surgical techniques and adjuvant drug therapy are improving,survival of patients with pancreatic cancer still has not been significantly improved.Long non-coding RNA are a class of non-coding transcripts longer than 200 nucleotides.Recent studies show long non-coding RNA is closely related to pancreatic cancer cells,apoptosis,metastasis and drug resistance.LncRNA plays an important role in the diagnosis,treatment and prognosis of pancreatic cancer.In this article we reviewed the role of long noncoding RNA and their significance in pancreatic carcinoma.

Induced pluripotent stem cell (iPS cell) opened a new way to stem cell research,iPS cells can differentiate into hepatocytes in vitro gradually,this breakthrough makes the iPS cells have become a promising clinical application source.During the process of iPS cells to hepatocytes,a variety of cytokines regulate gene expression by coordinating various liver cell growth signal to promote iPS cells into hepatocytes differentiation and maturation.This article summarizes the relevant cytokines and their role in iPS cells in hepatocytes differentiation.

BACKGROUND: A skull defect is inevitable after decompression treatment for traumatic brain injury. Titanium mesh as the most recognized skull repair material has good biocompatibility and has been widely used in clinical practice. However, the timing for skull repair after brain injury is still in dispute.OBJECTIVE: To compare the changes of brain perfusion and the recovery of neurological function in patients with skull defects before and after early and late-stage titanium mesh repair based on CT perfusion technique.METHODS: This was a single-center, prospective, observational clinical trial that was completed at the Taihe Hospital,Hubei University of Medicine in Hubei Province, China. Eighty-six patients with craniocerebral injury who had undergone decompression with removal of bone flap from January 2013 to January 2016 were recruited and subjected to skull repair using titanium mesh. All the patients were randomized into two groups: test group (n=40) with early skull repair within 1-3 months after decompression and control group (n=46) with late-stage skull repair within 6-12 months after decompression. CT perfusion technology was used to observe changes of brain perfusion at 3 days operatively and at 10 days postoperatively. The Barthel index was evaluated at 30 days postoperatively. The trial was registered with ClinicalTrial.gov (identifier: NCT03222297) on July 12th, 2017. The study protocol was approved by the Ethics Committee of Taihe Hospital with the approval No. 2012 (08), and performed in accordance with the Declaration of Helsinki,formulated by the World Health Organization and the hospital's ethical requirements for human research. All the patients and their families were voluntary to participate in the trial, were fully informed of the trial process, and then signed the informed consent prior to the initialization of the trial.RESULTS AND CONCLUSION: The postoperative cerebral blood volume and cerebral blood flow at the parietal cortex on the side of skull defect and at the cortex in the defect region were significantly higher in the two group than the baseline (P < 0.05), while the time to peak was lower than the baseline (P < 0.05). Compared with the control group,significantly higher cerebral blood volume and cerebral blood flow as well as shorter time to peak were observed in the test group (P < 0.05). The Barthel index of the test group was also significantly higher than that of the control group at 30 days postoepratively (P < 0.05). Overall, early skull repair with titanium mesh is helpful to improve the cerebral blood perfusion at the affected side and the recovery of neurological function. In addition, CT perfusion technology is a safe and effective method to monitor hemodynamic changes in the brain.

Aim To study the characteristics of KCNQ2/3 potassium channel expressed in CHO cells and its modulation by M_1 receptor.Methods KCNQ2 and KCNQ3 potassium channels and M_1 receptor were co-expressed in CHO cells.Whole cell patch-clamp techniques was used to observe the characteristics of KCNQ2/3 current,its modulation by the M_1 receptor,and the effects of the common potassium channel blockers.Results KCNQ2/3 current recorded in CHO cells was a slow-activation low-threshold non-inactivating,voltage-dependent outward potassium current.KCNQ2/3 current was elicited at about-60 mV,V_(1/2)(-26.8?1.2) mV and the deactivation current fitted two exponential function,with ?_(fast) of 101ms and ?_(slow) of 309 ms.The channel was not sensitive to common pharmacological blockers such as 4-AP,Ba~(2+) and TEA,but was inhibited significantly by linopirdine,with a IC_(50) of(6.5?0.83) ?mol?L~(-1).Acetylcholine suppressed the KCNQ2/3 current reversibly via M_1 receptor,with a IC_(50) of(0.7?0.05) ?mol?L~(-1).Conclusion KCNQ2 and KCNQ3 channels are the molecular basis of M-current observed in neuronal cells.KCNQ2/Q3 current expressed in CHO cells has similar characteristics as that seen in neuronal M-current.Linopirdine is a powerful blocker of KCNQ2/3 channel and acetylcholine inhibits the current by muscarinic M_1 receptor.This experiment has laid a solid basis for further study of M-current and KCNQ2/3 current,and is important for the study of neurological diseases relating to alteration of M-current,such as convulsion,epilepsy and Alzheimers disease.

ObjectiveTo investigate the efficacy and safety of laparoscope combined with choledochoscopic lithotomy for cholangiolithiasis.MethodsClinical data of 172 patients with cholangiolithiasis treated in the Central People's Hospital of Zhanjiang, Guangdong Province between January 2009 and June 2014 were retrospectively studied. Among the 172 patients, 65 were males and 107 were females with the average age of (44±7) years old. The informed consents of all patients were obtained and the local ethical committee approval had been received. According to the different surgical procedures, the patients were divided into the laparoscope combined with choledochoscopic lithotomy group (minimally invasive group,n=85) and the traditional open lithotomy group (traditional group,n=87). The patients in the minimally invasive group underwent laparoscopic common bile duct exploration + choledochoscopic lithotomy, while the patients in the traditional group underwent open common bileduct exploration + T-tube drainage. The perioperative conditions, postoperative complications and surgical curative effect of the two groups were compared. The data of the two groups were compared usingt test , Chi-square test or Fisher's exact probability test.Results The intraoperative blood loss of the minimally invasive group was (76±20) ml, which was significantly lower than (206±87) ml of the traditional group (t=-13.42,P<0.05). The postoperative evacuation time, defecation time and time of recovery to semi-liquid diet were respectively (2.4±1.0), (4.2±2.1) and (4.5±1.0) d, which were signiifcantly shorter than (3.5±1.5), (5.3±1.4) and (4.9±1.5) d of the traditional group (t=-5.645,-4.051,-2.053;P<0.05). The postoperative length of hospital stay of the minimally invasive group was (7.3±2.5) d, which was signiifcantly shorter than (9.5±2.7) d of the traditional group (t=-5.542,P<0.05). The incidence of incision fat liquefaction or poor healing of the minimally invasive group was 1% (1/85), which was significantly lower than 8% (7/87) of the traditional group (χ2=4.575,P<0.05). The cure rate of the minimally invasive group and the traditional group was both 91% and no signiifcant difference was observed (χ2=0.002,P>0.05). ConclusionsLaparoscope combined with choledochoscopic lithotomy for cholangiolithiasis has the same efifcacy with open lithotomy and has the advantages of high safety, quick postoperative recovery and short length of hospital stay.

Objective To observe the effect of quercetin on mechanical allodynia,astrocyte activation,and upregulation of pain-related transient receptor potential vanilloid 1(TRPV1)and P2X purinoceptor 3(P2X3)in mice with paclitaxel-induced peripheral neuropathy.Methods Twenty-four C57BL/6 mice were divided randomly into control,model,and model+quercetin groups(n=8 mice per group).Paclitaxel(total dose 8 mg/kg)was injected intraperitoneally into mice in the model and model+quercetin groups to establish the model.Mice in the control group were injected intraperitoneally with the same volume of vehicle.On day 8 after the first injection,mice in the model+quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle.Mechanical pain was measured by the von Frey test.Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence.Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot.Results(1)Compared with model group,the mechanical pain of mice in model+quercetin group were relieved.(2)Compared with model group,the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of model+quercetin group were alleviated(P＜0.05).Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy.This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.