Rapid health technology assessment of four oral Chinese patent medicines in treatment of functional gastrointestinal disorders / 中国中药杂志

To provide proof of the evidence-based medicine and decision-making information for the clinical decision of functional gastrointestinal disorders(FGIDs), this study evaluated and compared the efficacy, safety, and economy of four oral Chinese patent medicines(CPMs) in the treatment of FGIDs using the method of rapid health technology assessment. The literature was systematically retrieved from CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library and ClinicalTrials.gov from the establishment of the databases to May 1, 2022. Two evaluators screened out the literature, extracted data, evaluated the quality of the literature, and descriptively analyzed the results according to the prepared standard. Eventually, 16 studies were included, all of which was rando-mized controlled trial(RCT). The results showed that Renshen Jianpi Tablets, Renshen Jianpi Pills, Shenling Baizhu Granules, and Buzhong Yiqi Granules all had certain effects on the treatment of FGIDs. Renshen Jianpi Tablets treated FGIDs and persistent diarrhea. Shenling Baizhu Granules treated diarrhea with irritable bowel syndrome and FGIDs. Buzhong Yiqi Granules treated diarrhea with irritable bowel syndrome, FGIDs, and chronic diarrhea in children. Renshen Jianpi Pills treated chronic diarrhea. The four oral CPMs all have certain effects on the treatment of FGIDs and have specific advantages for specific patients. Compared with other CPMs, Renshen Jianpi Tablets have higher clinical universality. However, there are problems such as insufficient clinical research evidence, generally low quality of evidence, lack of comparative analysis among medicines, and lack of academic evaluation. More high-quality clinical research and the economic research should be carried out in the future, so as to provide more evidence for the evaluation of the four CPMs.

PKCɛ mediates substance P inhibition of GABAA receptors-mediated current in rat dorsal root ganglion / 华中科技大学学报（医学）（英德文版）

The mechanism underlying the modulatory effect of substance P (SP) on GABA-activated response in rat dorsal root ganglion (DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA (1-1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons (89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA (1-1000 μmol/L) evoked a depolarizing response in 236 out of 257 (91.8%) DRG neurons examined with intracellular recordings. Application of SP (0.001-1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1 (NK1) receptors antagonist spantide but not by L659187 and SR142801 (1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C (PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca(2+)-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.

PKCɛ mediates substance P inhibition of GABAA receptors-mediated current in rat dorsal root ganglion / 华中科技大学学报（医学）（英德文版）

The mechanism underlying the modulatory effect of substance P (SP) on GABA-activated response in rat dorsal root ganglion (DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA (1-1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons (89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA (1-1000 μmol/L) evoked a depolarizing response in 236 out of 257 (91.8%) DRG neurons examined with intracellular recordings. Application of SP (0.001-1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1 (NK1) receptors antagonist spantide but not by L659187 and SR142801 (1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C (PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca²⁺-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.

The characteristics of resting membrane potential on smooth muscle cells and endothelial cells in guinea pigs cochlea spiral artery / 中国应用生理学杂志

<p><b>OBJECTIVE</b>A variety of inner ear disease is related to microcirculation disturbance of inner ear, but smooth muscle cells (SMC) and endothelial cells (EC) of the spiral modiolar artery (SMA), which is the main blood supply to the inner ear, physiological feature is not very clear.</p><p><b>METHODS</b>In this study, two-intracellular microelectrode recording technique and cell staining techniques to study the SMC and EC resting membrane potential characteristics and communication links between cells of SMA.</p><p><b>RESULTS</b>Study found that SMC and EC have high and low resting membrane potential state, two state of the resting membrane potential of cells to ACh and high K+ response is completely different. The different types of cells, EC-EC, SMC-SMC and SMC-EC, can simultaneously record by two-microelectrode, two cell resting membrane potential can also be a double-high RP, double-low RP and one high- and one low- RP. Experiment recorded in one high- and one low- RP are the SMC-EC types, and ECs initial membrane potential are high potential, SMCs membrane potential are low initial potential. The double-high and double-low RP can be SMC-SMC or EC-EC or SMC-EC types.</p><p><b>CONCLUSION</b>The results show that SMC and EC in the 0.3 - 0.5 mm range, similar type of cells have very good communication, can function together to maintain good and consistent, heterogeneous cell performance is more different.</p>

18β-glycyrrhetinic acid inhibits outward current of vascular smooth muscle cells of arterioles / 生理学报

The aim of the present study was to investigate the effect of 18β-glycyrrhetinic acid (18βGA) on the membrane current of vascular smooth muscle cells (VSMCs) in arteriole. Guinea pig anterior inferior cerebellar artery (AICA) and mesenteric artery (MA) were isolated, and single VSMCs were harvested using digestion with papain and collagenase IA. Outward currents of the VSMCs were recorded by whole-cell patch clamp technique. Results were shown as below: (1) 1 mmol/L 4-AP and 1 mmol/L TEA both could partially inhibit the whole-cell current of VSMCs in arterioles. (2) 18βGA inhibited the outward current of VSMCs in a concentration-dependent manner. The inhibitory rates of 10, 30 and 100 μmol/L 18βGA on the membrane current of VSMCs (+40 mV) were (25.3 ± 7.1)%, (43.1 ± 10.4)% and (68.4 ± 3.9)% respectively in AICA, and (13.2 ± 5.6)%, (34.2 ± 4.0)% and (59.3 ± 7.3)% respectively in MA. There was no significant difference between the inhibitory effects of 18βGA on AICA and MA. 18βGA also inhibited the outward current of VSMCs in a voltage-dependent manner. 18βGA induced a more pronounced inhibition of the outward current from 0 to +40 mV, especially at +40 mV. (3) With the pretreatment of 10 mmol/L TEA, the inhibitory effect of 18βGA on the membrane current of VSMCs was significantly abolished. These results suggest that the outward current of VSMCs in arterioles is mediated by voltage-dependent K(+) channels (K(v)) and big conductance calcium-activated K(+) channels (BK(Ca)), which can be inhibited by 18βGA in concentration- and voltage-dependent way.

The distribution and mechanism of coronary arteriole cell resting membrane potential in guinea pigs / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the distribution and mechanism of coronary arteriole (CA) cell resting membrane potential (RP) in guinea pigs.</p><p><b>METHODS</b>Cell RP was recorded by intracellular microelectrode in isolated guinea pig coronary arteriole (diameter < 100 microm).</p><p><b>RESULTS</b>(1) Experiments were carried out in 112 cells with a mean RP of (-65 +/- 4.2)mV, the distribution of coronary arteriole cell RP fitted by Gaussian function was bimodal, one peak was -43 mV termed high RP, the other was -74 mV termed low RP. 10 mmol/L K+ and 3 micromol/ L acetylcholine(ACh) induced hyperpolarization in high-RP cells with (-7.4 +/- 0.87) mV (n = 13) and (-15 +/- 1.24) mV (n = 16) respectively, and induced depolarization in low-RP cells with (9.6 +/- 1.2) mV (n = 23) and (8.7 +/- 0.69) mV (n = 15) respectively. (2) The inward rectifier K+ channel (K(ir)) blocker Ba2+ caused concentration-dependent depolarization in low-RP cells with an EC50 of 120 micromol/L 100 micromol/L Ba2+ or higher could shift low-RP cells to high-RP state, the response of these cells to high K+ and ACh became a hyperpolarization.</p><p><b>CONCLUSION</b>The distribution of coronary vascular cell RP is bimodal, high K+ and ACh induce different responses in low and high RP cells. The two RP states are exchangeable mainly due to all-or-none conductance changes of K(ir).</p>

Protective effect of taurine on myocardial ischemia and reperfusion injury in rats / 中国临床药理学与治疗学

Aim To research the protective effect and mechanisms of taurine on myocardial ischemia and reperfusion injury in rats. Methods Myocardial ischemia reperfusion models were established in SD rats. The effects of taurine on the size of myocardial infarction and the changes of activity of SOD , and the levels of MDA and NO in myocardium and plasma of rats with myocardial ischemia and reperfusion injury were observed. Results In rats with myocardial ischemia and reperfusion injury, the taurine could reduce the size of myocardial infarction (P