Expression changes of NaV channel subunits correlate with developmental maturation of electrophysiological characteristics of rat cerebellar Purkinje neurons / 南方医科大学学报

OBJECTIVE@#To investigate the variations in the expression of voltage-gated sodium (Nav) channel subunits during development of rat cerebellar Purkinje neurons and their correlation with maturation of electrophysiological characteristics of the neurons.@*METHODS@#We observed the changes in the expression levels of NaV1.1, 1.2, 1.3 and 1.6 during the development of Purkinje neurons using immunohistochemistry in neonatal (5-7 days after birth), juvenile (12-14 days), adolescent (21-24 days), and adult (42-60 days) SD rats. Using whole-cell patch-clamp technique, we recorded the spontaneous electrical activity of the neurons in ex vivo brain slices of rats of different ages to analyze the changes of electrophysiological characteristics of these neurons during development.@*RESULTS@#The expression of NaV subunits in rat cerebellar Purkinje neurons showed significant variations during development. NaV1.1 subunit was highly expressed throughout the developmental stages and increased progressively with age (P < 0.05). NaV1.2 expression was not detected in the neurons in any of the developmental stages (P > 0.05). The expression level of NaV1.3 decreased with development and became undetectable after adolescence (P < 0.05). NaV1.6 expression was not detected during infancy, but increased with further development (P < 0.05). NaV1.1 and NaV1.3 were mainly expressed in the early stages of development. With the maturation of the rats, NaV1.3 expression disappeared and NaV1.6 expression increased in the neurons. NaV1.1 and NaV1.6 were mainly expressed after adolescence. The total NaV protein level increased gradually with development (P < 0.05) and tended to stabilize after adolescence. The spontaneous frequency and excitability of the Purkinje neurons increased gradually with development and reached the mature levels in adolescence. The developmental expression of NaV subunits was positively correlated with discharge frequency (r=0.9942, P < 0.05) and negatively correlated with the excitatory threshold of the neurons (r=0.9891, P < 0.05).@*CONCLUSION@#The changes in the expression levels of NaV subunits are correlated with the maturation of high frequency electrophysiological properties of the neurons, suggesting thatmature NaV subunit expressions is the basis of maturation of electrophysiological characteristics of the neurons.

Prediction of plasma protein binding rate based on machine learning / 中国药科大学学报

@#Predicting the protein binding rate of drugs in plasma is helpful to us in understanding the pharmacokinetic characteristics of drugs, with much value of reference for early research on drug discovery. In this study, plasma protein binding rate information of 2 452 clinical drugs were collected.Two pieces of software, Molecular Operating Environment (MOE) and Mordred, were used to calculate molecular descriptors, which were used as input features of the model.Extreme gradient boosting (XGBoost) algorithm and random forest (RF) algorithm were then used to build a machine learning model.The results showed that, compared with MOE, the prediction performance of the constructed model was better using the molecular descriptor calculated by Mordred as the input of the model.The prediction performance results of the model constructed using the XGBoost algorithm and the RF algorithm were similar, and the R2 of the optimal model were both 0.715.According to the research results, it can be concluded that the drug plasma protein binding rate is closely related to some physical and chemical properties of the drug molecule, such as water solubility, octanol/water partition coefficient and conjugated double bonds.Using these parameters to predict the plasma protein binding rate of drugs has the advantages of convenience and efficiency, which can provide reference for related pharmacokinetic studies.

Expression and functional assessment of solute carrier 26A transporter family in HEK-293 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To express solute carrier 26A proteins in HEK-293 cells and explore their functions.</p><p><b>METHODS</b>SLC26A-eGFP plasmids were transiently transfected into HEK-293 cells, and the nonlinear capacitance of the cells expressing SLC26A proteins was measured by whole-cell patch recording.</p><p><b>RESULTS</b>All the SLC26A transporters were expressed on the membrane of HEK-293 cells. Each member of the SLC26A transporter family showed robust nonlinear capacitance, which represented their binding capability with anions.</p><p><b>CONCLUSION</b>The SLC26A transporters expressed on HEK cells show similar functions as expected in tissue environment. The plasmids we constructed facilitate structural and functional study of SLC26A transporters.</p>

Curative effect of Milrinone combined with Esmolol in treatment of severe hand-foot-and-mouth disease / 中华实用儿科临床杂志

Obgective To observe the effect of Milrinone combined with Esmolol in the treatment of severe hand-foot-and-mouth disease (HFMD) so as to improve the prognosis.Methods Eighty-two cases of children with critically severe HFMD,who were hospitalized in the Intensive Care Unit of Xuzhou Children's Hospital,were enrolled in the study from may of 2013 to June of 2014,and were randomly divided into a control group and an observation group.The control group was given intravenous Milrinone,and the observation group was given Milrinone combined with Esmolol.The heart rate (HR),systolic blood pressure (SBP),cardiac output (CO),left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP),norepinephrine (NE) were detected on admission and checked again 1 hour and 48 hours again after treatment.The changes in the above indicators were compared before and after therapy to evaluate the clinical curative effect.Results (1) There was no significant difference in the HR,SBP,CO,LVEF,BNP and NE between the 2 groups before treatment(all P ＞ 0.05).(2) The HR,SBP,CO and LVEF of 2 groups were significantly improved after 1 hour treatment compared with those before treatment (all P ＜ 0.05),and the BNP and NE of the control group were not obviously improved compared with those before therapy (all P ＞ 0.05),but the significant changes were seen in the observation group (all P ＜ 0.05).Forty-eight hours after the treatment,all the observed indicators in 2 groups were significantly improved compared with those before treatment(all P ＜ 0.01).(3)Compared with control group,the HR,SBP,CO,LVEF and BNP of the observation group were significantly improved after 1 hour treatment (t =2.08,2.12,-2.11,-2.37,2.07,all P ＜ 0.05),but the NE of the observation group had no obvious improvement (t =0.83,P ＞ 0.05).All the observed indicators of the observation group were significantly improved compared with the control group after 48 hours treatment(t =3.76,2.48,-2.70,-2.27,5.37,2.74,all P ＜ 0.05).Conclusions Milrinone combined with Esmolol can significantly improve the cardiac function and the vital signs of the children with critically severe HFMD,which can be recommended clinically.

Influential factors of healthy children′s heart rate turbulence / 实用医学杂志

Objective To analyze the influential factors of healthy children′s heart rate turbulence (HRT). Methods One hundred and six healthy children with ventricular premature beat (VPB) were selected in this study and the correlation among HTR parameters as turbulence onset (TO) and turbulence lope (TS) and age, gender, basic heart rate, the number of VPBs were analyzed. Results It was observed that among three age groups, TO decreased with the age, and the difference was statistically significant (P 0.05). TS increased with the age, and intergroup difference was statistically significant (P 0.05). TO and TS decreased with the decline of heart rate (r = 0.494, P < 0.00; r = -0.569,P < 0.00 respectively), and the correlation between TO and HR, TS and HR was found.The number of VPBs had no significant correlation with TO or TS (r = 0.104,P = 0.290; r = 0.122,P =0.212). Conclusions The results demonstrate that influenced by age and basic heart rate, healthy children′s HRT increases with the age and the decline of heart rate. Therefore, the reference index of children′s HRT should differ from that of adults, which requires further evaluation.

Functional refinement of bushy cells in the anterior ventral cochlear nucleus precedes hearing onset in neonatal rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the development of the electrophysiological property of bushy cells in the anterior ventral cochlear nucleus (AVCN) of neonatal Sprague Dawley (SD) rats.</p><p><b>METHODS</b>The development of action potential and spontaneous miniature excitatory postsynaptic currents (mEPSCs) in AVCN bushy cells were investigated by whole-cell patch-clamp technique in SD rats during the postnatal days 5-21 (P5-21). The half band width of the action potential (AP), 10%-90% risetime and decay tau of the mEPSCs were analyzed.</p><p><b>RESULTS</b>The AP of the bushy cells became faster with age from P5 to P21 and stopped changing around the period of hearing onset, as evidenced by the alteration of half band width of the AP. The time accuracy of mEPSCs of the bushy cells also increased with age and stabilized around hearing onset as shown by briefer 10%-90% rise time and decay tau of mEPSCs in P14/P21 than in P7.</p><p><b>CONCLUSION</b>The functional refinement of the bushy cells in the AVCN precedes hearing onset in neonatal rats.</p>

Effects of astragalus and its active ingredients on ischemia reperfusion injury in isolated guinea-pig heart / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the effects of astragalus (AST) , total flavone of astragalus (TFA), total saponins of astragalus (TSA) and astragalus polysaccharides (APS) on ischemia/reperfusion (40 min/60 min) injury in isolated guinea-pig heart.</p><p><b>METHODS</b>Isolated guinea-pig hearts underwent ischemia, then followed by K-H perfusion (I/R group), AST (60 mg/L),AST (60 mg/L), TFA (60 mg/L), TSA (60 mg/L) and APS (60 mg/L) perfusion (n = 6 each).Isolated hearts without ischemia serve as control group (n = 6). Activity of lactate dehydrogenas (LDH) and creatine kinase (CK) in effluent were measured.Infarct size, myocardial superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were also determined.</p><p><b>RESULTS</b>Compared to control hearts, heart rate, coronary flow and myocardial superoxide dismutase (SOD) activity were significantly reduced, while LDH and CK in effluent as well as myocardial MDA were significantly increased in the I/R hearts during reperfusion (all P < 0.05), these changes could be partly reversed by AST and TFA perfusion.Infarct size was also significantly reduced in AST (11.9 ± 2.03) % and TFA (13.31 ± 1.17) % treated hearts compared to that in I/R group (18.9 ± 2.27) % (all P < 0.01).</p><p><b>CONCLUSIONS</b>The findings indicate that AST and TFA could attenuate I/R injury in isolated guinea-pig heart possibly through enhancing the activity of SOD and reducing lipid peroxidation.</p>