In the clinical reports, the E1784K mutation in SCN5A is recognized as a phenotypic overlap between the long QT syndrome （LQT3） and the Brugada syndrome （BrS） in the characteristics of electrocardiograms （ECGs） ...In the clinical reports, the E1784K mutation in SCN5A is recognized as a phenotypic overlap between the long QT syndrome （LQT3） and the Brugada syndrome （BrS） in the characteristics of electrocardiograms （ECGs） since the mutation can influence sodium channel functions. However it is still unclear if the E1784K mutation-induced sodium ionic channel alterations account for the overlap at tissue level. Thsu, a detailed computational model is developed to underpin the functional impacts of the E1784K mutation on the action potential （AP）, the effective refractory period （ERP） and the abnormal ECG. Simulation results stlggest＇that the E1784K mutation-induced sodium channel alterations are insufficient to produce the phenotypic overlap between LQT3 and BrS, and the overlap may arise from the complicated effects of the E1784K mutation-induced changes in sodium channel currents with an increase of the transient outward current ITo or a decrease of the L-type calcium current ICaL .展开更多
Background Atrial fibrillation （AF） is the most common arrhythmia encountered in clinical practice and hy- pertension has been well established to be the most common medical condition associated with AF. The present...Background Atrial fibrillation （AF） is the most common arrhythmia encountered in clinical practice and hy- pertension has been well established to be the most common medical condition associated with AF. The present study aimed to explore the expression of ionic channels in atrial myocytes, the main mechanisms of atrial electrical remodeling, under ambient pressure stimulation. Methods A resealable device that could provide and maintain a certain pressure was designed and used. Subconfluent cells were maintained in a pressure culture device which placed in a carbon dioxide incubator for 24 h. The pressure gradient was set to 0 mmHg, 20 mmHg and 40 mmHg. The mRNA and protein levels of the calcium channel, potassium channel and sodium channel were assayed using real-time PCR, and Western blot respectively. Results We found that mRNA and protein expression of Cav1.2 and protein expression of Cav3.1, Kv11.1 and Kv4.3 are significantly decreased after pressure stimulation. Pressure stimulation up-regulated the mRNA and protein expression of Kv1.5 and Kir2.1 but could not regulate mRNA or protein expression of Nay1.5. Conclusions Our results represent a potential pathogenic mechanism of hypertension involved in atrial electrical remodeling and provide enlightening insights to the prevention and treatment of AF.展开更多
To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes Methods Membrane ionic channels were studied in enzymat...To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes Methods Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats (SHRs) left ventricular myocytes using the whole cell configuration of patch clamp technique, with normal Wistar rats ventricular myocytes as controls We observed depolarizing currents (sodium current, I Na ; L type calcium current, L I Ca ) and repolarizing currents (inward rectifier potassium current, I K1 ; delayed rectifier potassium current, I K; transient outward potassium current, I to ) and compared the differences between normal and hypertrophied myocytes Results The heart to body weight ratio of Wistar rats and SHRs was 3 70±0 29?mg/g and 5 66±0 46?mg/g, respectively ( P <0 001), and the mean cell membrane capacitances were 189 94±56 59?pF and 280 68±67 98?pF, respectively ( P <0 05) These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes The amplitude of L I ca of SHRs (1944±466 8?pA) was significantly greater than that of Wistar rats (1136±383 3?pA) ( P <0 001), and the current density was 6 93±1 71?pA/pF and 6 19±2 85?pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged (56 01±13 36?ms vs 43 63±17 89?ms, P <0 001) The amplitude of I Na of SHRs (6132 5±1162 9?pA) was significantly greater than that of Wistar rats (3613 9±794 44?pA) ( P <0 001), but there was no difference when normalized to cell capacitance (24 61±6 72?pA/pF vs 24 95±6 99?pA/pF) Channel activation and inactivation time constants were also the same The amplitude of I K of SHRs (3461 5±1967 10?pA) was greater than that of Wistar rats (2302 4±893 72?pA) ( P <0 05), but there was no difference when normalized to cell capacitance (12 38±5 46 ?pA/pF vs 11 86±3 59?pA/pF) The inward portion of I K1 of SHRs was significantly lower than that of Wistar rats (11 3±2 26?pA/pF vs 14 3±3 00?pA/pF, P <0 05), but there was no difference in the outward portion (2 360±0 86?pA/pF vs 2 957±1 27? pA/pF) The current density of I to of SHRs (8 21±6 64?pA/pF) was significantly lower than that of Wistar rats (19 16±6 17?pA/pF) ( P <0 001), but channel kinetics were similar, suggesting that the reduction of I to may result from the decrease in channel number Conclusions Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1 there was an increase of L I ca , I Na and I k, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2 I to was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of I to may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity Therefore, the reduction of I to in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling展开更多
The concentration difference in the near-surface region of lithium metal is the main cause of lithium dendrite growth.Resolving this issue will be key to achieving high-performance lithium metal batteries(LMBs).Herein...The concentration difference in the near-surface region of lithium metal is the main cause of lithium dendrite growth.Resolving this issue will be key to achieving high-performance lithium metal batteries(LMBs).Herein,we construct a lithium nitrate(LiNO_(3))-implanted electroactiveβphase polyvinylidene fluoride-co-hexafluoropropylene(PVDF-HFP)crystalline polymorph layer(PHL).The electronegatively charged polymer chains attain lithium ions on the surface to form lithium-ion charged channels.These channels act as reservoirs to sustainably release Li ions to recompense the ionic flux of electrolytes,decreasing the growth of lithium dendrites.The stretched molecular channels can also accelerate the transport of Li ions.The combined effects enable a high Coulombic efficiency of 97.0%for 250 cycles in lithium(Li)||copper(Cu)cell and a stable symmetric plating/stripping behavior over 2000 h at 3 mA cm^(-2)with ultrahigh Li utilization of 50%.Furthermore,the full cell coupled with PHL-Cu@Li anode and Li Fe PO_(4) cathode exhibits long-term cycle stability with high-capacity retention of 95.9%after 900 cycles.Impressively,the full cell paired with LiNi_(0.87)Co_(0.1)Mn_(0.03)O_(2)maintains a discharge capacity of 170.0 mAh g^(-1)with a capacity retention of 84.3%after 100 cycles even under harsh condition of ultralow N/P ratio of 0.83.This facile strategy will widen the potential application of LiNO_(3)in ester-based electrolyte for practical high-voltage LMBs.展开更多
The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KC...The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.展开更多
Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction （ AMI）, so as to explore the ionic mechanism of...Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction （ AMI）, so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups： AMI group, simvastatin intervention group （ Statin group） and sham-operated control group （CON）. Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg^-1·d^-1 （Statin group） or placebo （AMI group） for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, including sodium current （INa）, L-type calcium current （Ica-L） and transient outward potassium current （Ito）. Results （1） There was not significant difference in serum cholesterol concentration among three groups. （2） The peak INa current density （at -30 mV） was significantly decreased in AMI group （ -25.26±5.28, n = 13 ）, comparing with CON （ - 42. 78± 5.48, n = 16）, P 〈 0. 05, while it was significantly increased in Statin group （ - 39.83 ±5.65 pA/pF, n = 12） comparing with AMI group, P 〈0. 01 ; The peak Ica-L current density （ at 0 mV） was significantly decreased in AMI group （ -3. 43 ±0. 92 pA/pF, n = 13） comparing with CON （ -4. 56 ±1.01 pA/pF, n = 15）, P 〈0. 05, while it was significantly increased in Statin group （ -4. 18±0. 96 pA/pF, n = 12） comparing with AMI group, P 〈0. 05; The Ito current density （ at ＋ 60 mV） was significantly decreased in AMI group （ 11.41 ± 1.94 pA/pF, n = 13 ） comparing with CON （17.41 ±3.13 pA/pF, n = 15）, P 〈0. 01, while it was significantly increased in Statin group （16. 11 ± 2. 43 pA/pF, n = 14） comparing with AMI group, P 〈 0. 01. Conclusions AMI induces significant down-regulation of INa, Ica-L and Ito. Pretreatment with simvastatin could attenuate this change without lowering the serum cholesterol level, suggesting that simvastatin could reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.展开更多
Objectives Previous studies demonstrated that angiotensin receptor antagonists had effects on some potassium channels in guinea pig myo- cytes and cloned channels that expressed in human car- diac myocytes. This study...Objectives Previous studies demonstrated that angiotensin receptor antagonists had effects on some potassium channels in guinea pig myo- cytes and cloned channels that expressed in human car- diac myocytes. This study determined the direct effects of Valsartan on IcaL, INa, IKur, IKl and Itol in isolated human atrial myocytes. Methods and Results Specimens of right atrial appendage tissue were ob- tained from 39 patients with coronary artery and valvu- lar heart diseases during cardiopuhnonary bypass proce- dure. Pre - operation cardiac rhythm was sinus (SR) in 19 patients and was atrial fibrillation (AF) in the others. Single atrial myocyte was isolated by enzymatic dissociation with the chunk method. The ionic currents were recorded using the whole cell configuration of the voltage clamp technique. ICaL and Itol densities in AF patients were significantly lower than those in SR pa- tients by 74% and 60% , respectively, while IK1 density was significantly higher by 34% at command potential of - 120 mV. With 10 μmol/L Valsartan, INa density was significantly decreased by 59% in SR patients and by 66% in AF patients. IKur and IK1 density were sig- nificantly decreased in only AF patients by 31% and 23% , respectively. Conclusions Conclusions De- creased ICaL and Itol and increased IK1 at hyperpolarizing potentials in AF patients' atrial myocytes may result from the electrophysiological remodeling by AF. Val- sartan significantly decreases INa, IK1 and IKur current densities in AF patients' myocyte, but decreases only INa in SR patients' myocyte, suggesting that Valsartanmay be beneficial to the recovering of remolded atria.展开更多
Objective To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes after acute myocardial infarction (AMI,so as to explore the ionic mechanism of statin treatment for antiarrhy...Objective To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes after acute myocardial infarction (AMI,so as to explore the ionic mechanism of statin treatment for antiarrhythmia.Methods Fourty-five New Zeland rabbits were randomly divided into three groups:AMI group,simvastatin intervention group （statin group） and sham-operated control group （CON）.Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg·kg<sup>-1</sup>·d<sup>-1</sup> （Statin group） or placebo （AMI group）for 3 days.Twenty-four hours later,single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region.Whole cell patch clamp technique was used to record membrane ionic currents,including sodium current (I<sub>Na</sub>),L-type calcium current (I<sub>Ca-L</sub>) and transient outward potassium current (I<sub>to</sub>).Results①There was no significant difference in serum cholesterol concentration among three groups.②The peak I<sub>Na</sub> current density （at-30 mV） was significantly decreased in AMI group （-23.26±5.18） compared with CON （-42.78±5.48,P【0.05）,while it was significantly increased in Statin group （-39.23±5.45） compared with AMI group （P【0.01）;The peak I<sub>Ca-L</sub> current density （at 0 mV） was significantly decreased in AMI group （-3.23±0.91） compared with CON （-4.56±1.01,P【0.05）,while it was significantly increased in Statin group （- 4.18±0.95） compared with AMI group （P【0.05）;The I<sub>to</sub> current density（at +60 mV） was significantly decreased in AMI group（10.41±1.93）compared with CON （17.41±3.13,P【0.01）,while it was significantly increased in Statin group（16.21±2.42）compared with AMI group （P【0.01）.Conclusions AMI induces significant down-regulation of I<sub>Na</sub>,I<sub>Ca-L</sub> and I<sub>to</sub>.Pretreatment with simvastatin could attenuate this change without lowering the serum cholesterol level,suggesting that simvastatin reverse this electrical remodeling,thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.展开更多
The practical application of the Li metal anode has long been hindered by the uncontrolled growth of Li dendrites,heterogeneous and fragile solid electrolyte interface(SEI)layer,and large volume swelling.Herein,a robu...The practical application of the Li metal anode has long been hindered by the uncontrolled growth of Li dendrites,heterogeneous and fragile solid electrolyte interface(SEI)layer,and large volume swelling.Herein,a robust artificial SEI layer,polyaryoxadiazole lithium sulfonate(PODLi),was successfully fabricated to stabilize the interface between the Li metal and electrolyte.The lithiophilic PODLi film afforded fast ionic transport channels to form a dendrite-free,lithium fluoride-rich anode.The Li@Cu-PODLi symmetric cell achieved excellent cycling performance at a high current density of 10 mA cm^(−2) with an areal capacity of 10 mAh cm^(−2) for more than 770 h.A full cell with the LiFPO_(4) cathode exhibited ultralong-term stable operation over 500 cycles at a high current density of 3.45 mA cm^(−2) with a low-capacity decay rate of 0.038%per cycle.This work demonstrates a cost-effective and scalable strategy for high-energy-density Li metal batteries.展开更多
基金Supported by the National Natural Science Foundation of China(61001167,61172149)~~
文摘In the clinical reports, the E1784K mutation in SCN5A is recognized as a phenotypic overlap between the long QT syndrome （LQT3） and the Brugada syndrome （BrS） in the characteristics of electrocardiograms （ECGs） since the mutation can influence sodium channel functions. However it is still unclear if the E1784K mutation-induced sodium ionic channel alterations account for the overlap at tissue level. Thsu, a detailed computational model is developed to underpin the functional impacts of the E1784K mutation on the action potential （AP）, the effective refractory period （ERP） and the abnormal ECG. Simulation results stlggest＇that the E1784K mutation-induced sodium channel alterations are insufficient to produce the phenotypic overlap between LQT3 and BrS, and the overlap may arise from the complicated effects of the E1784K mutation-induced changes in sodium channel currents with an increase of the transient outward current ITo or a decrease of the L-type calcium current ICaL .
基金supported by National Natural Science Foundation of China(No.81370295,81470440)Guangdong Natural Science Foundation(No.2015A030313657)Medical Science Foundation of Guangdong(No.A2015542)
文摘Background Atrial fibrillation （AF） is the most common arrhythmia encountered in clinical practice and hy- pertension has been well established to be the most common medical condition associated with AF. The present study aimed to explore the expression of ionic channels in atrial myocytes, the main mechanisms of atrial electrical remodeling, under ambient pressure stimulation. Methods A resealable device that could provide and maintain a certain pressure was designed and used. Subconfluent cells were maintained in a pressure culture device which placed in a carbon dioxide incubator for 24 h. The pressure gradient was set to 0 mmHg, 20 mmHg and 40 mmHg. The mRNA and protein levels of the calcium channel, potassium channel and sodium channel were assayed using real-time PCR, and Western blot respectively. Results We found that mRNA and protein expression of Cav1.2 and protein expression of Cav3.1, Kv11.1 and Kv4.3 are significantly decreased after pressure stimulation. Pressure stimulation up-regulated the mRNA and protein expression of Kv1.5 and Kir2.1 but could not regulate mRNA or protein expression of Nay1.5. Conclusions Our results represent a potential pathogenic mechanism of hypertension involved in atrial electrical remodeling and provide enlightening insights to the prevention and treatment of AF.
文摘To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes Methods Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats (SHRs) left ventricular myocytes using the whole cell configuration of patch clamp technique, with normal Wistar rats ventricular myocytes as controls We observed depolarizing currents (sodium current, I Na ; L type calcium current, L I Ca ) and repolarizing currents (inward rectifier potassium current, I K1 ; delayed rectifier potassium current, I K; transient outward potassium current, I to ) and compared the differences between normal and hypertrophied myocytes Results The heart to body weight ratio of Wistar rats and SHRs was 3 70±0 29?mg/g and 5 66±0 46?mg/g, respectively ( P <0 001), and the mean cell membrane capacitances were 189 94±56 59?pF and 280 68±67 98?pF, respectively ( P <0 05) These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes The amplitude of L I ca of SHRs (1944±466 8?pA) was significantly greater than that of Wistar rats (1136±383 3?pA) ( P <0 001), and the current density was 6 93±1 71?pA/pF and 6 19±2 85?pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged (56 01±13 36?ms vs 43 63±17 89?ms, P <0 001) The amplitude of I Na of SHRs (6132 5±1162 9?pA) was significantly greater than that of Wistar rats (3613 9±794 44?pA) ( P <0 001), but there was no difference when normalized to cell capacitance (24 61±6 72?pA/pF vs 24 95±6 99?pA/pF) Channel activation and inactivation time constants were also the same The amplitude of I K of SHRs (3461 5±1967 10?pA) was greater than that of Wistar rats (2302 4±893 72?pA) ( P <0 05), but there was no difference when normalized to cell capacitance (12 38±5 46 ?pA/pF vs 11 86±3 59?pA/pF) The inward portion of I K1 of SHRs was significantly lower than that of Wistar rats (11 3±2 26?pA/pF vs 14 3±3 00?pA/pF, P <0 05), but there was no difference in the outward portion (2 360±0 86?pA/pF vs 2 957±1 27? pA/pF) The current density of I to of SHRs (8 21±6 64?pA/pF) was significantly lower than that of Wistar rats (19 16±6 17?pA/pF) ( P <0 001), but channel kinetics were similar, suggesting that the reduction of I to may result from the decrease in channel number Conclusions Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1 there was an increase of L I ca , I Na and I k, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2 I to was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of I to may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity Therefore, the reduction of I to in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling
基金the financial support from the National Natural Science Foundation of China(Nos.22205191 and 52002346)the Science and Technology Innovation Program of Hunan Province(No.2021RC3109)+1 种基金the Natural Science Foundation of Hunan Province,China(No.2022JJ40446)Guangxi Key Laboratory of Low Carbon Energy Material(No.2020GXKLLCEM01)。
文摘The concentration difference in the near-surface region of lithium metal is the main cause of lithium dendrite growth.Resolving this issue will be key to achieving high-performance lithium metal batteries(LMBs).Herein,we construct a lithium nitrate(LiNO_(3))-implanted electroactiveβphase polyvinylidene fluoride-co-hexafluoropropylene(PVDF-HFP)crystalline polymorph layer(PHL).The electronegatively charged polymer chains attain lithium ions on the surface to form lithium-ion charged channels.These channels act as reservoirs to sustainably release Li ions to recompense the ionic flux of electrolytes,decreasing the growth of lithium dendrites.The stretched molecular channels can also accelerate the transport of Li ions.The combined effects enable a high Coulombic efficiency of 97.0%for 250 cycles in lithium(Li)||copper(Cu)cell and a stable symmetric plating/stripping behavior over 2000 h at 3 mA cm^(-2)with ultrahigh Li utilization of 50%.Furthermore,the full cell coupled with PHL-Cu@Li anode and Li Fe PO_(4) cathode exhibits long-term cycle stability with high-capacity retention of 95.9%after 900 cycles.Impressively,the full cell paired with LiNi_(0.87)Co_(0.1)Mn_(0.03)O_(2)maintains a discharge capacity of 170.0 mAh g^(-1)with a capacity retention of 84.3%after 100 cycles even under harsh condition of ultralow N/P ratio of 0.83.This facile strategy will widen the potential application of LiNO_(3)in ester-based electrolyte for practical high-voltage LMBs.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273458 to Jinfei Chen)the Start-up Fund for the Recruited Talents of the First Affiliated Hospital of Wenzhou Medical University(Grant No.2021QD025 to Jinfei Chen)。
文摘The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.
文摘Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction （ AMI）, so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups： AMI group, simvastatin intervention group （ Statin group） and sham-operated control group （CON）. Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg^-1·d^-1 （Statin group） or placebo （AMI group） for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, including sodium current （INa）, L-type calcium current （Ica-L） and transient outward potassium current （Ito）. Results （1） There was not significant difference in serum cholesterol concentration among three groups. （2） The peak INa current density （at -30 mV） was significantly decreased in AMI group （ -25.26±5.28, n = 13 ）, comparing with CON （ - 42. 78± 5.48, n = 16）, P 〈 0. 05, while it was significantly increased in Statin group （ - 39.83 ±5.65 pA/pF, n = 12） comparing with AMI group, P 〈0. 01 ; The peak Ica-L current density （ at 0 mV） was significantly decreased in AMI group （ -3. 43 ±0. 92 pA/pF, n = 13） comparing with CON （ -4. 56 ±1.01 pA/pF, n = 15）, P 〈0. 05, while it was significantly increased in Statin group （ -4. 18±0. 96 pA/pF, n = 12） comparing with AMI group, P 〈0. 05; The Ito current density （ at ＋ 60 mV） was significantly decreased in AMI group （ 11.41 ± 1.94 pA/pF, n = 13 ） comparing with CON （17.41 ±3.13 pA/pF, n = 15）, P 〈0. 01, while it was significantly increased in Statin group （16. 11 ± 2. 43 pA/pF, n = 14） comparing with AMI group, P 〈 0. 01. Conclusions AMI induces significant down-regulation of INa, Ica-L and Ito. Pretreatment with simvastatin could attenuate this change without lowering the serum cholesterol level, suggesting that simvastatin could reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.
文摘Objectives Previous studies demonstrated that angiotensin receptor antagonists had effects on some potassium channels in guinea pig myo- cytes and cloned channels that expressed in human car- diac myocytes. This study determined the direct effects of Valsartan on IcaL, INa, IKur, IKl and Itol in isolated human atrial myocytes. Methods and Results Specimens of right atrial appendage tissue were ob- tained from 39 patients with coronary artery and valvu- lar heart diseases during cardiopuhnonary bypass proce- dure. Pre - operation cardiac rhythm was sinus (SR) in 19 patients and was atrial fibrillation (AF) in the others. Single atrial myocyte was isolated by enzymatic dissociation with the chunk method. The ionic currents were recorded using the whole cell configuration of the voltage clamp technique. ICaL and Itol densities in AF patients were significantly lower than those in SR pa- tients by 74% and 60% , respectively, while IK1 density was significantly higher by 34% at command potential of - 120 mV. With 10 μmol/L Valsartan, INa density was significantly decreased by 59% in SR patients and by 66% in AF patients. IKur and IK1 density were sig- nificantly decreased in only AF patients by 31% and 23% , respectively. Conclusions Conclusions De- creased ICaL and Itol and increased IK1 at hyperpolarizing potentials in AF patients' atrial myocytes may result from the electrophysiological remodeling by AF. Val- sartan significantly decreases INa, IK1 and IKur current densities in AF patients' myocyte, but decreases only INa in SR patients' myocyte, suggesting that Valsartanmay be beneficial to the recovering of remolded atria.
文摘Objective To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes after acute myocardial infarction (AMI,so as to explore the ionic mechanism of statin treatment for antiarrhythmia.Methods Fourty-five New Zeland rabbits were randomly divided into three groups:AMI group,simvastatin intervention group （statin group） and sham-operated control group （CON）.Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg·kg<sup>-1</sup>·d<sup>-1</sup> （Statin group） or placebo （AMI group）for 3 days.Twenty-four hours later,single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region.Whole cell patch clamp technique was used to record membrane ionic currents,including sodium current (I<sub>Na</sub>),L-type calcium current (I<sub>Ca-L</sub>) and transient outward potassium current (I<sub>to</sub>).Results①There was no significant difference in serum cholesterol concentration among three groups.②The peak I<sub>Na</sub> current density （at-30 mV） was significantly decreased in AMI group （-23.26±5.18） compared with CON （-42.78±5.48,P【0.05）,while it was significantly increased in Statin group （-39.23±5.45） compared with AMI group （P【0.01）;The peak I<sub>Ca-L</sub> current density （at 0 mV） was significantly decreased in AMI group （-3.23±0.91） compared with CON （-4.56±1.01,P【0.05）,while it was significantly increased in Statin group （- 4.18±0.95） compared with AMI group （P【0.05）;The I<sub>to</sub> current density（at +60 mV） was significantly decreased in AMI group（10.41±1.93）compared with CON （17.41±3.13,P【0.01）,while it was significantly increased in Statin group（16.21±2.42）compared with AMI group （P【0.01）.Conclusions AMI induces significant down-regulation of I<sub>Na</sub>,I<sub>Ca-L</sub> and I<sub>to</sub>.Pretreatment with simvastatin could attenuate this change without lowering the serum cholesterol level,suggesting that simvastatin reverse this electrical remodeling,thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.
基金supported by the National Key Research and Development Program of China(project no.2022YFA1205201)the State Key Laboratory of Polymer Materials Engineering,China(grant no.sklpme2022-2-04).
文摘The practical application of the Li metal anode has long been hindered by the uncontrolled growth of Li dendrites,heterogeneous and fragile solid electrolyte interface(SEI)layer,and large volume swelling.Herein,a robust artificial SEI layer,polyaryoxadiazole lithium sulfonate(PODLi),was successfully fabricated to stabilize the interface between the Li metal and electrolyte.The lithiophilic PODLi film afforded fast ionic transport channels to form a dendrite-free,lithium fluoride-rich anode.The Li@Cu-PODLi symmetric cell achieved excellent cycling performance at a high current density of 10 mA cm^(−2) with an areal capacity of 10 mAh cm^(−2) for more than 770 h.A full cell with the LiFPO_(4) cathode exhibited ultralong-term stable operation over 500 cycles at a high current density of 3.45 mA cm^(−2) with a low-capacity decay rate of 0.038%per cycle.This work demonstrates a cost-effective and scalable strategy for high-energy-density Li metal batteries.
