The Relationship of Anatomical Localizations of Hiatal Clamp and Oesophagogastric Junction with Body Mass Index / Relación entre las Localizaciones Anatómicas de la Pinza Hiatal y la Unión Esofagogástrica con el Índice de Masa Corporal

SUMMARY: In our study, we aimed to reveal the relationship between the anatomical localizations measured and the Body Mass Index (BMI) in patients scheduled for upper gastrointestinal endoscopy. In this study, anatomical localizations of the hiatal clamp and oesophagogastric junction in 189 female and 137 male patients who applied to the hospital with different gastrointestinal system complaints and underwent esophagogastroduodenoscopy (EGD) were investigated depending on BMI. In addition, the data were compared with the patients' complaints before EGD and the diagnoses they received after EGD. SPSS Statistics 22 (IBM Corp. Turkey) program was used for statistical analysis and p0.05). On the other hand, it was determined that the hiatal clamp distance and the distance of the oesophagogastric junction increased as the height and weight increased (p38. As a result of the study, it can be said that BMI values, hiatal clamp distance and oesophagogastric junction localizations may change in relation to height and weight.

En este estudio, buscamos revelar la relación entre las localizaciones anatómicas y el Índice de Masa Corporal (IMC) en pacientes programados para endoscopía digestiva alta. Se investigaron las localizaciones anatómicas de la pinza hiatal y la unión esofagogástrica en 189 mujeres y 137 hombres que acudieron al hospital con diferentes problemas del sistema gastrointestinal los cuales fueron sometetidos a una esofagogastro- duodenoscopia (EGD) dependiendo del IMC. Además, los datos se compararon con las quejas de los pacientes antes de la EGD y los diagnósticos que recibieron después de la EGD. Se utilizó el programa SPSS Statistics 22 (IBM Corp. Turquía) para el análisis estadístico y el valor de p0,05). Por otro lado, se determinó que la distancia de la pinza hiatal y la unión esofagogástrica aumentaba con la altura y el peso corporal (p38. Como resultado del estudio, se puede decir que los valores de IMC, la distancia de pinzamiento hiatal y las localizaciones de la unión esofagogástrica pueden cambiar en relación con la altura y el peso.

Effect of microparticles derived from bone marrow mesenchymal stem cells on cardiomyocyte hypertrophy and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of microparticles(MPs)derived from bone marrow mesenchymal stem cells(BMSCs) on myocardial hypertrophy and its mechanism.Methods The osteogenic differentiation and adipogenic differentiation of mesenchymal stem cells(MSCs) were induced. After isolation and purification,the morphological characteristics were observed by transmission electron microscope,and the MPs surface antigen was identified by flow cytometry. Myocardial hypertrophy model was induced by using isoprenaline(ISO)in rats,which were measured for the cardiac structure and function by echocardiography,and then detected for various indexes of the heart and isolated left ventricle. Single ventricular myocytes of rats were acutely isolated and divided into control group(Control group),cardiomyocyte hypertrophy group(ISO group),MPs group(MPs group),and MPs supernatant group(Supernatant group). The mRNA expressions of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)were detected by qRTPCR. The expression levels of calmodulin-dependent protein kinaseⅡ（CaMKⅡ）and phosphorylated calmodulin-dependent protein kinaseⅡ（p-CaMKⅡ）were detected by ELISA. The L-type calcium current(LCa-L)in single ventricular myocyte of various groups was recorded by whole-cell patch clamp.Results The bone nodules of MSCs osteogenic differentiation turned red after alizarin red staining,and lipid droplets of adipogenic differentiation turned red after oil red O staining;Under transmission electron microscope,MPs membrane had a complete structure,a clear outline and a diameter of about200 nm;The positive rates of CD29 and CD90 on the surface of MPs were(98. 24 ± 0. 82)% and(97. 69 ± 1. 83)%,respectively. Compared with Control group,the left ventricular end diastolic dimension(LVEDD)reduced signifi-cantly(t =5. 065,P < 0. 05),while the interventricular septum end-diastolic dimension(IVSd),left ventricular posterior wall dimension(LVPWd),heart weight to body weight ratio(HW/BW),and heart weight to tibial length ratio(HW/Tibia)significantly increased in ISO group(t = 4. 013,2. 368,4. 392,5. 043 and 6. 120,respectively,each P < 0. 05),indicating that the hypertrophic model was successfully established. The expression levels of ANP and BNP mRNA in hypertrophic cardiomyocytes of rats in ISO group were significantly higher than those in Control group(t = 25. 120 and18. 261,respectively,each P < 0. 01);While the expression levels of ANP and BNP mRNA in MPs group significantly reduced after incubation with 48 μg/mL MPs for 48 h compared with ISO group(t = 12. 110 and 3. 526,respectively,each P < 0. 05);The expression levels of CaMK Ⅱand p-CaMKⅡ in ISO group were significantly higher than those in Control group(t = 3. 278 and 4. 181,respectively,each P < 0. 05),while the expression of p-CaMK Ⅱ in MPs group decreased significantly(t = 5. 420,P < 0. 05);The calcium current density in ISO group was significantly higher than that in Control group(t = 15. 261,P < 0. 01),while that in MPs group was significantly lower than that in ISO group(t =6. 216,P < 0. 05).Conclusion MSC-MPs can significantly inhibit ISO-induced cardiomyocyte hypertrophy in rats,which is related to its down-regulation of cardiomyocyte CaMKⅡ and inhibition of L-type calcium channel.

Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes / 药学学报

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

The threshold value for identifying insulin resistance (HOMA-IR) in an admixed adolescent population: A hyperglycemic clamp validated study

ABSTRACT Objectives: To validate the homeostasis model assessment (HOMA) of insulin resistance (IR) as a surrogate to the hyperglycemic clamp to measure IR in both pubertal and postpubertal adolescents, and determine the HOMA-IR cutoff values for detecting IR in both pubertal stages. Subjects and methods: The study sample comprised 80 adolescents of both sexes (aged 10-18 years; 37 pubertal), in which IR was assessed with the HOMA-IR and the hyperglycemic clamp. Results: In the multivariable linear regression analysis, adjusted for sex, age, and waist circumference, the HOMA-IR was independently and negatively associated with the clamp-derived insulin sensitivity index in both pubertal (unstandardized coefficient - B = −0.087, 95% confidence interval [CI] = −0.135 to −0.040) and postpubertal (B = −0.101, 95% CI, −0.145 to −0.058) adolescents. Bland-Altman plots showed agreement between the predicted insulin sensitivity index and measured clamp-derived insulin sensitivity index in both pubertal stages (mean = −0.00 for pubertal and postpubertal); all P > 0.05. The HOMA-IR showed a good discriminatory power for detecting IR with an area under the receiver operator characteristic curve of 0.870 (95% CI, 0.718-0.957) in pubertal and 0.861 (95% CI, 0.721-0.947) in postpubertal adolescents; all P < 0.001. The optimal cutoff values of the HOMA-IR for detecting IR were > 3.22 (sensitivity, 85.7; 95% CI, 57.2-98.2; specificity, 82.6; 95% CI, 61.2-95.0) for pubertal and > 2.91 (sensitivity, 63.6; 95% CI, 30.8-89.1, specificity, 93.7; 95%CI, 79.2-99.2) for postpubertal adolescents. Conclusion: The threshold value of the HOMA-IR for identifying insulin resistance was > 3.22 for pubertal and > 2.91 for postpubertal adolescents.

Preliminary application of transesophageal echocardiography in transapical mitral valve repair with Memoclip / 中华超声影像学杂志

Objective:To explore the value of transapical catheter of mitral valve repair (MVR) with Memoclip device in the management of moderate to severe and severe mitral regurgitation (MR) guided by transesophageal echocardiography (TEE).Methods:Fifteen patients with moderate to severe and severe MR in Hefei High-tech Cardiovascular Hospital from December 2021 to October 2022 were prospectively selected. Mitral valve morphology and length, regurgitation severity, left ventricular ejection fraction and pulmonary venous Doppler spectra were carefully evaluated before MVR by TEE.Intraprocedural TEE was performed to guide the MVR including transseptal catheterization, alignment of the clip delivery system, assessment of leaflet capture, clip deployment, post-clip deployment assessment, and withdrawal of the clip delivery system. The position and coaptation length of the clips, the mitral orifice morphology, residual mitral valve regurgitation and pressure gradient were evaluated after MVR.Meanwhile, the complications were monitored throughout the procedure.Results:Among the 15 patients, 12 were implanted with 1 clip and 3 were implanted with 2 clips, respectively. No complications occurred. There were 13 patients with mild regurgitation and 2 showed to moderate mitral regurgitation 1 month later after MVR, and 13 remained mild and 2 maintained moderate regurgitation 3 months later. Significant differences were found in maximal MR area (MRA-max), maximal and mean mitral valve pressure gradient (MVPG-max, MVPG-mean) and mitral valve area (MVA) among the 5 observation time points (all P<0.05). MRA-max, MVA and MVPG-mean were significantly decreased immediately and 3 months after the procedure ( P<0.001). No significant stenosis was found in mitral valve after MVR. Conclusions:MVR with Memoclip is safe, effective, easy to operate in treating patients with moderate to severe and severe MR. TEE plays a key role in perioperative MVR with Memoclip through apical catheterization.

Inhibitory effects of a TRPM4 inhibitor 9-phenanthrol on electrical activity of INS-1 pancreatic β-cells / 药学学报

The Ca2+-activated monovalent cation selective transient receptor potential melastatin 4 (TRPM4) channel expressed in pancreatic β-cells is implicated in the β-cell function and insulin secretion, but how pharmacological function of TRPM4 channel affects membrane excitability of β-cells remains largely unknown. Here, we report that pharmacological inhibition of TRPM4 by specific inhibitor 9-phenanthrol attenuates electrical activities of pancreatic β-cells. In whole-cell current clamp recordings, 9-phenanthrol results in inhibition of action potential frequency induced by tolbutamide of the INS-1 pancreatic β-cells in a dose-dependent manner with an IC50 value of 14.99 ± 7.93 μmol·L-1. Similarly, 9-phenanthrol also inhibited action potential firing in INS-1 cells stimulated by current injection. Further recordings of β-cells demonstrate the significant inhibitory effects on action potential peak and action potential amplitude by 9-phenanthrol. Taken together, our results show the involvement of TRPM4 channel function in pancreatic β-cells depolarization and action potential, it provides pharmacological experimental methods and theoretical support for the study of TRPM4 channel in pancreatic β-cells.

Effects of propofol on glutamatergic neuronal activity in paraventricular thalamus / 药学学报

This study explored the effects of propofol on the activity of glutamatergic neurons in the paraventricular thalamus (PVT) and the underlying mechanisms at the molecular level using whole-cell patch-clamp techniques. Acute brain slices containing the PVT were obtained from 8 weeks old C57BL/6J mice. The electrophysiological characteristics of PVT neurons were recorded in current-clamp mode, then single-cell sequencing was used to identify neuronal types. The firing frequencies before, during, and after propofol or intralipid application were recorded as FB, FD and FW; and the membrane potentials were recorded as MPB and MPD. Picrotoxin (PTX) was used to block inhibitory gamma-aminobutyric acid type A (GABAA) receptors during the application of propofol at 10 μmol·L-1. Then, GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) were recorded, and the effects of 10 μmol·L-1 propofol were investigated. The animal experiments were approved by the Medical Animal Administrative Committee of Shanghai Medical College Fudan University. The results showed that there were no significant differences in FB, FD and FW during intralipid and 2 μmol·L-1 propofol application. With propofol at 5, 10 and 20 μmol·L-1, FD decreased significantly when compared with FB, and FW increased significantly as compared with FD (P < 0.01). The inhibition degree of the three concentration groups was significantly different (P < 0.01). In addition, with propofol at 20 μmol·L-1, MPD hyperpolarized significantly (P < 0.01). In the presence of PTX, 10 μmol·L-1 propofol could not suppress the firing frequency of PVT glutamatergic neurons. Propofol at 10 μmol·L-1 prolonged the decay time of sIPSCs (P < 0.01) and mIPSCs (P < 0.05), and increased the amplitude (P < 0.01) of mIPSCs of PVT glutamatergic neurons. Together, these results indicate that propofol can inhibit the activity of PVT glutamatergic neurons in a concentration-dependent and reversible manner, and the effect is likely to be mediated by postsynaptic GABAA receptors.

Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity

Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.

Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation / 中西医结合学报

OBJECTIVE@#To investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca2+ channels, and insulin secretion.@*METHODS@#We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca2+ channels and insulin secretion, respectively.@*RESULTS@#Ferulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca2+ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca2+ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca2+-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca2+ influx through L-type Ca2+ channel. Our data also suggest that this may be a direct, nongenomic action.@*CONCLUSION@#This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca2+ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.

Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment / 神经科学通报·英文版

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.

Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2 in vivo and in vitro / 中国结合医学杂志

OBJECTIVE@#To investigate whether Suxiao Jiuxin Pills (SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation (VF) agent.@*METHODS@#VF was induced by isoproterenolol (ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current (CaV1.2), voltage-dependent sodium channel current (INa), rapid and slow delayed rectifier potassium channel current (IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential (AP) and pseudo-electrocardiography (pseudo-ECG) models.@*RESULTS@#SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration (IC50) value of 16.9 mg/L (SJP-30 mg/L, -32.8 ± 6.1 pA; Verapamil, -16.2 ±1.8 pA; vs. control, -234.5 ±16.7 pA, P<0.01, respectively). The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly (SJP vs. control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration, transiting VF into sinus rhythm in pseudo-ECG.@*CONCLUSION@#SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.

George W. Crile (1864-1943); excepcional cirurgião americano / George W. Crile (1864-1943); excepcional cirujano estadounidense / George W. Crile (1864-1943); exceptional American surgeon

George W. Crile (1864-1943); excepcional cirurgião americano, que serviu no Corpo Médico do Exército durante a Guerra Hispano-Americana. Durante a Primeira Guerra Mundial, foi diretor cirúrgico do American Ambulance Hospital em Neuilly, na França. Ajudou fundar o American College of Surgeons em 1913, foi membro e diretor não apenas dessa organização, mas também da American Medical Association, da American Surgical Association, da Royal Academy of Surgeons e da Royal Academy of Medicine (Reino Unido). Em 1921, foi cofundador da Cleveland Clinic em Cleveland, Ohio, EUA. Foi um importante médico cujas pesquisas e escritos incluíam choque cirúrgico, função glandular, pressão arterial e transfusões, neurose de guerra e os efeitos da cirurgia em tempos de guerra. Ele também foi um cirurgião extraordinário e prolífico que introduziu inovações no tratamento cirúrgico de muitas patologias. Embora sua pesquisa tenha sido publicada há muito tempo, suas contribuições para a medicina continuam sendo fundamentais para a prática clínica nas salas de cirurgia e unidades de terapia intensiva atuais.

George W. Crile (1864-1943) fue un excepcional cirujano estadounidense que sirvió en el Cuerpo Médico del Ejército durante la Guerra Hispanoamericana. Durante la Primera Guerra Mundial fue director quirúrgico del American Ambulance Hospital de Neuilly (Francia). Ayudó a fundar el Colegio Americano de Cirujanos en 1913 y fue miembro y director no sólo de esta organización, sino también de la Asociación Médica Americana, la Asociación Quirúrgica Americana, la Real Academia de Cirujanos y la Real Academia de Medicina (Reino Unido). En 1921 fue cofundador de la Cleveland Clinic de Cleveland (Ohio, EE.UU.). Fue un importante médico cuyas investigaciones y escritos abarcaron el shock quirúrgico, la función glandular, la presión arterial y las transfusiones, la neurosis de guerra y los efectos de la cirugía en tiempos de guerra. También fue un cirujano extraordinario y prolífico que introdujo innovaciones en el tratamiento quirúrgico de muchas patologías. Aunque sus investigaciones se publicaron hace mucho tiempo, sus aportaciones a la medicina siguen siendo fundamentales para la práctica clínica en los quirófanos y unidades de cuidados intensivos actuales.

George W. Crile (1864-1943) was an exceptional American surgeon who served in the Army Medical Corps during the Spanish-American War. During the First World War, he was surgical director of the American Ambulance Hospital in Neuilly, France. He helped found the American College of Surgeons in 1913 and was a member and director not only of this organization, but also of the American Medical Association, the American Surgical Association, the Royal Academy of Surgeons and the Royal Academy of Medicine (UK). In 1921, he co-founded the Cleveland Clinic in Cleveland, Ohio, USA. He was an important physician whose research and writings included surgical shock, glandular function, blood pressure and transfusions, war neurosis and the effects of wartime surgery. He was also an extraordinary and prolific surgeon who introduced innovations in the surgical treatment of many pathologies. Although his research was published long ago, his contributions to medicine remain fundamental to clinical practice in today's operating rooms and intensive care units.

Effects of early sleep deprivation on depressive-like behavior and hippocampus synaptic plasticity in adult depression model mice / 中华行为医学与脑科学杂志

Objective:To investigate the effects of early sleep deprivation(SD) on depressive-like behavior and hippocampus synaptic plasticity in adult mice with chronic unpredictable mild stress(CUMS) model.Methods:Thirty 2-week-old clean grade male mice were randomly divided into control group (CON group), CUMS group and SD + CUMS group according to the random number table, with 10 mice in each group. The mice in SD + CUMS group were subjected with sleep deprivation for 4 hours once a day during puberty (3 ~ 6 weeks old), and then were stimulated by CUMS after adulthood (9 weeks old). The mice in CUMS group were subjected with CUMS at the age of 9 weeks. And the mice in CON group were not given any intervention.The depressive-like behavior was evaluated by body weight, sugar water preference, tail suspension test and forced swimming test.The density of dendritic spines of basal and apical neurons in hippocampal CA1 was measured by Golgi staining, the frequency and amplitude of miniature excitatory postsynaptic current(mEPSC) of pyramidal neurons in the hippocampal CA1 region of mice were measured by electro-physiological patch clamp technique.Graphpad prism 7.0 software was used for statistical analysis and mapping. One-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparison.Results:(1) After stress modeling, there were significant differences in body weight, sugar water preference percentage, forced swimming immobility time and tail suspension time among the three groups ( F=71.63, 39.82, 44.13, 43.07, all P<0.01). Compared with CON group, the mice in CUMS group and SD+ CUMS group had lower body weight ((25.51±0.37) g, (22.92±0.31) g, (20.12±0.27) g, both P<0.01), lower sugar water percentage preference ((87.40±1.65) %, (63.42±3.33) %, (49.68±3.70)%, both P<0.01), longer immobile time of forced swimming ((34.30±5.32) s, (119.20±12.03) s, (153.80±9.17) s, both P<0.01) and longer immobile time of tail suspension test((115.20±8.19)s, (156.80±4.35) s, (192.00±4.12) s, both P<0.01). Compared with CUMS group, SD+ CUMS group had lower body weight ( P<0.01), lower sugar water preference percentage ( P<0.05), longer immobile time in forced swimming test( P<0.05) and longer immobile time in tail suspension test( P<0.01). (2) Golgi staining results showed that the densities of dendritic spines of apical neurons and basal neurons in hippocampal CA1 area of the three groups were significantly different ( F=38.41, 41.34, both P<0.01). The densities of dendritic spines of basal and apical hippocampal neurons in CUMS group and SD+ CUMS group were lower than those in CON group ((7.74±0.22)/10 μm, (6.58±0.27)/10 μm, (5.00±0.13)/10 μm, both P<0.01), ((8.90±0.23)/10 μm, (7.63±0.30)/10 μm, (6.01±0.14)/10 μm, both P<0.01). Compared with CUMS group, the mice in SD+ CUMS group had lower densities of dendritic spines of basal and apical hippocampal neurons(both P<0.01). (3) Electrophysiological results showed that there were significant differences in the frequency and amplitude of mEPSC in hippocampal pyramidal neurons of the three groups ( F=38.90, 63.37, both P<0.01). Compared with CON group, the frequency and amplitude of mEPSC in pyramidal neurons of CA1 in CUMS group and SD+ CUMS group were significantly lower ((0.39±0.03)Hz, (0.20±0.02)Hz, (0.07±0.02)Hz, both P<0.01; (9.98±0.31)pA, (7.74±0.21)pA, 6.36±0.13)pA, both P<0.01). Compared with CUMS group, the frequency and amplitude of mEPSC in SD+ CUMS group were lower (both P<0.01). Conclusion:Adolescent sleep deprivation aggravates depressive behavior and hippocampus synaptic plasticity impairment in adult CUMS model mice.

Study of electrophysiological mechanism of dopamine inhibiting insulin secretion by Kv channels / 中国药理学通报

Aim To study the electrophysiological mechanism of dopamine inhibiting insulin secretion hv voltage-dependent potassium ( Kv) channels.Methods Islets and (3 cells were isolated from male SD rats.D,-like receptor agonist ( SKP38393), D2-like receptor agonist (Quinpirole) and antagonist (Epiclopride) were used according to the experiment.Insulin secretion was detected by insulin radioimmunoassay.Whole-cell j J patch-clamp technique was applied to detect Kv channel currents and action potential duration of p cells.Di- BAC4(3) staining was used to observe membrane potential.Results SKF38393 did not affect insulin secretion and the Kv channel currents.Quinpirole signifi cantly inhibited insulin secretion and increased Kv channel currents.Dopamine significantly inhibited insulin secretion, increased Kv channel currents and shortened action potential duration of p cells, which could be reversed by epiclopride.In addition, dopamine de-creased membrane potential of INS-1 cells.Conclusions Dopamine inhibits insulin secretion by acting on D2-like receptors, resulting in actived Kv channels, shortened action potential duration and decreased cell membrane potential.

Baicalin enhances middle cerebral artery smooth muscle cells BK channel-mediated outward currents in SD rats / 中国药理学通报

Aim To study the effeet of baicalin on middle cerebral arterv in SD rats.Methods The j changes of middle cerebral artery diameter were observed using a pressure myograph system.The whole- cell and inside-out patch-clamp recording were used to detected the electrophysiological features of single vascular smooth muscle cells.Results Baicalin dilated the middle cerebral artery segment of SD rats in a con- centration-dependent manner.IbTX blocked baicalin - mediated relaxation.Baicalin enhanced the outward current of middle cerebral artery smooth muscle cells in a concentration-dependent manner.IbTX blocked ba- icalin-mediated outward current.Baicalin increased BK channel open probabilities.Conclusions Baicalin enhances the outward current mediated by BK channel and relaxes the middle cerebral arterv in SD rats.

The insulinotropic effects and its relevant mechanism of telmisartan in rats / 中国药理学通报

Aim To investigate the insulinotropic effect of telmisartan anrl the underlying electrophysiological mechanism.Methods Islets and cells were isolated from Wistar rats.Islets were incubated with drugs un¬der different conditions, then supernatant liquid was collected for insulin secretion.Intracellular Ca" + ( Ca'+ j) levels of (3-cells were measured by calcium imaging technology.Patch-clamp technology was ap¬plied to detect effects on voltage-gated potassium chan¬nel ( Kv ) , and voltage-gated calcium channel ( VGCC ).Results Not affecting insulin secretion un¬der low glucose condition, telmisartan dose-dependent- ly stimulated insulin secretion under high glucose con¬ dition, and stimulation was enhanced with increasing glucose concentration.Acute increases of Ca' + concentration were elicited by telmisartan under high glucose condition.Telmisartan decreased current den¬sity of Kv channel, and increased VGCC current densi¬ty.Conclusions Telmisartan enhanced Ca~+ ; lev¬els of p-cells through its action on Kv channel and VGCC, thereby amplifying glucose-stimulated insulin secretion.

The effect of HMS-01 on stably expressed hERG channel currents in HEK293 cells detected with the manualpatch clamp method / 药学实践杂志

Objective To test the cardiac toxicity of new compound HMS-01 and evaluate the safety profile for clinical trials. Methods Manualpatch clamp method was used to measure human Ether-a-go-go-Related Gene (hERG) potassium channel currents with different concentrations of HMS-01. Cisapride was selected as the positive control drug. HMS-01 was diluted to the concentration of 0.3, 1, 3, 10 and 30 µmol/L and applied to the cells. The changes in electrical currents were recorded and the inhibition rate was calculated. Results At the highest concentration of 30µmol/L, the inhibitory rate of HMS-01 on hERG channel was less than 30%. There was no obvious inhibitory effect compared with cisapride. Conclusion Compared with the cisapride, HMS-01 has no obvious inhibitory effect on hERG channel and has no cardiotoxicity.

Isolation, identification and electrophysiological activity of BmK M2 from Buthus martensii Karsch venom / 中国药科大学学报

@#This study aimed to isolate and identify novel toxin peptides targeting voltage-gated sodium channels (VGSGs) from the venom of the Buthus martensii Karsch (BmK) scorpion. Using G50-gel filtration, HPLC, peptide fingerprinting and amino acid sequencing, a novel sodium channel modulator, BmK M2, was identified from BMK scorpion. BmK M2 is a relatively abundant long chain polypeptide toxin in BmK scorpion venom with a molecular weight of 7 235.59, consisting of 64 amino acids and 4 pairs of disulfide bonds.Sequence alignment showed that the amino acid sequence of BmK M2 had high sequence and structural similarity to that of the discovered sodium channel toxins of BmK M1, BmK M3 and BmK M9, etc.BmK M2 is a potential new sodium channel modulator.Electrophysiological results revealed that BmK M2 can significantly enhance the activation, delay the steady-state inactivation and closed-state inactivation of Nav1.7, but has no activity on Nav1.8.BmK M2 can be used as a novel peptide probe for the study of the structure and function of Nav1.7 and the development of drugs targeting Nav1.7.

Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation / 神经科学通报·英文版

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.