Objective To investigate the role of acid-sensing ion channel 1a(ASIC1a) in global cerebral ischemia-reperfusion injury in rats.Methods Forty male SD rats weighing 250-300 g were randomly divided into 4 groups (n =10 each): sham operation group (group S),cerebral ischemia-reperfusion group (group I/R),solvent control group (group SC) and group PcTX1 (a ASIC1 a blocker,group P).Global cerebral ischemia-reperfusion was induced by four-vessel occlusion.PcTX1(500 ng/ml)6 μl or solvent 6 μl was injected into the crerbral ventricular at the begining of reperfusion in groups P and SC respectively.The rats were sacrificed at 24 h of reperfusion,and then the hippocampi were removed for determination of Caspase-3,Bcl-2 and Bax protein expression and microscopic examination.Results Compared with group S,the expression of Caspase-3,Bcl-2 and Bax protein was up-regulated in groups I/R,SC and P (P ＜ 0.05).Compared with group I/R,the expression of Caspase-3 and Bax was down-regulated,and the expression of Bcl-2 was up-regulated in group P ( P ＜ 0.05).There was no significant difference in Caspase-3,Bcl-2 and Bax protein expression between groups I/R and SC (P ＞ 0.05).The histopathologic damage was ameliorated in group P as compared with group I/R.Conclusion ASIC1a can induce global cerebral ischemia-reperfusion injury in rats by up-regulating Caspase-3 and Bax expression,and down-regulating Bcl-2 expression and inducing apoptosis.

ObjectiveTo explore the effects of different doses of PcTx1,a specific blocker of acid-sensing ion channel 1a,on global cerebral ischemia/repedfusion (I/R) injury in rats,MethodsSixty adult male Sprague Dawley rats (weighing 250-300 g) were randomly divided into 6 grups ( n =10 each):sham operation group (group S),I/R group,different doses of PcTx1 ( 10 ng/ml,group P1 ; 25 ng/ml,group P2 ; 50 ng/ml,group P3 ;and 500 ng/ml,group P4 ) groups.Global cerebral ischemia was induced by the modified procedure of Pulsinelli 4-vessel occlusion.In groups P1,P2,P3 and P4,different doses of PcTx1 ( 10,25,50 and 500 ng/ml),6 μl each,were respectively injected into the lateral cerebral ventricle at the initiation of reperfusion,while equal volume of double distilled water was injected instead in group I/R.Six rats in each group were sacrificed at 24 h of reperfusion,and the brains were immediately removed,Thereafter,the contents of malondialdehyde (MDA),reduced glutathione (GSH) and ritric oxide (NO),the activities of constitutive NO synthase (eNOS) snd inducible NO synthase (iNOS) were detected in hippocampus.Four rats in each group were sacrificed at 72 h of reperfusion,and hematoxylin and eosin staining was used to observe the pathomorphological changes of the hippocampal neurons.ResultsCompared with group S,the other groups showed decreases in the contents of GSH,while increases in the contents of MDA and NO and the activities of cNOS and iNOS ( P ＜ 0.05 or 0.01 ).The contents of GSH increased,while the contents of MDA and NO and the activities of cNOS and iNOS decreased in groups P2,P3 and P4 compared with group I/R ( P ＜ 0.05 or 0.01).Compared with group P1,the contents of GSH increased,the contents of MDA and the activities of cNOS decreased in groups P2,P3 and P4,and the contents of NO and the activities of iNOS decreased in groups P3 and P4 ( P ＜ 0.05 or 0.01 ).Compared with group P2,the activities of iNOS decreased in groups P3 and P4(P ＜ 0.05 or 0.01).The damage to neurons in hippocampal CAI was severe in groups I/R and P1,but it was attenuated in groups P3 and P4.ConclusionPcTx1 25,50 and 500 ng/ml (6 μl)injected into lateral cerebral ventricle can attenuate global cerebral I/R injury in rats,and the dose 50 ng/ml (6 μl) is more suitable.

Objective To investigate the effects of gabapentin on high-voltage-activated calcium currents in dorsal root ganglion (DRG) neurons in mice with oxaliplatin-induced neuropathic pain (NP). Methods Pathogen-free male Kunming mice aged 6 weeks weighing 20-25 g were used in this study. NP was induced by injection of intraperitoneal oxaliplatin 3 mg/kg. Successful induction of NP was defined as the mechanical paw withdrawal threshold (MWT) measured at 3 d after oxaliplatin administration decreased to 40% of the baseline ( before administration of oxaliplatin). Forty-one mice in which NP was successfully induced were randomly divided into 2 groups: NP group ( n = 20) and gabapentin group (group G, n = 21 ). Another 10 normal mice served as control group (group C). At 3 days after oxaliplatin administration, gabapentin 100 mg/kg was injected intraperitoneally once a day for 3 consecutive days in group G, while C and NP groups received the equal volume of normal saline.MWT to von Fray filament stimulation was measured immediately before and 1-3 days after gabapentin administration (T1-4). After the last measurement of MWT, bilateral L4.5 DRG was collected and neurons were isolated. The high-voltage-activated calcium currents were recorded using whole-cell patch-clamp technique. The peak current density and the voltage where half of the current was activated ( Va1/2 ) or inactivated ( Vi 1/2 ) were calculated. Results Compared with group C, MWT at T1-4 was decreased, the peak current density and Vi1/2 were significantly increased in group NP, and MWT at T1 was decreased in group G ( P ＜ 0.05). There was no significant difference in the peak current density, Vi1/2 and Va1/2 between C and G groups ( P ＞ 0.05). MWT at T2-4 was significantly increased, while the peak current density and Vi1/2 were significantly decreased in group G compared with group NP (P ＜ 0.05). Conclusion Gabapentin can reduce oxaliplatin-induced NP in mice through inhibiting high-voltage-activated calcium currents and promoting the inactivation of the channels in DRG neurons.

Objective To investigate the role of mitochondrial permeability transition pore (mPTP) of hippocampal neurons in process of hydrogen-rich saline attenuating global cerebral ischemia-reperfusion (I/R) injury in rats.Methods Seventy-two male Sprague Dawley rats,weighing 250-300 g,were randomly divided into six groups ( n =12 each):sham operation group (group S),cerebral ischemia-reperfusion group (group IR),normal saline group (group NS),hydrogen-rich saline group (group H),atractyloside group (group A) and hydrogen-rich saline + atractyloside group (group HA).Global cerebral I/R injury was produced by four-vessel occlusion method.Bilateral vertebral arteries were cauterized.Then bilateral common carotid arteries were occluded for 15min and followed by reperfusion.In groups H and HA,hydrogen-rich saline 5 ml/kg was injected intraperitoneally immediately after reperfusion,while equal volume of normal saline was injected in the other four groups.The rats in groups A and HA received intracerebroventricular injection of atractyloside 15 μl 10 min before reperfusion,while groups NS and H received intracerebroventricular injection of equal volume of normal saline.After the neurological behavior was evaluated at 24 h of reperfusion,8 rats in each group were sacrificed and the hippocampi were immediately isolated and homogenized followed by density gradient centrifugation.The opening degree of mPTP was assayed with spectrophotometry and the mitochondrial membrane potential (MMP) was detected with Rhodamine 123 method.Four rats in each group were killed at 72 h of reperfusion and the brains were removed for microscopic examination of the area CA1 of the hippocampus and determination of the number of normal pyramidal neurons.Results Compared with group S,the neurological behavior was compromised,MMP was decreased and mPTP opening degree was enhanced in the other five groups ( P ＜ 0.05).The neurological behavior was better,MMP was increased and mPTP opening degree was decreased in groups H and HA as compared with group IR ( P ＜ 0.05).Compared with group H,the neurological behavior was compromised,MMP was decreased and mPTP opening degree was enhanced in group HA ( P ＜ 0.05).Compared with group IR,the number of normal pyramidal neurons at 72 h of reperfusion in the CA1 region of the hippocampus was higher in group HA ( P ＜0.05).The injury of the CA1 region of the hippocampus at 72 h of reperfusion was attenuated in group H as compared with groups IR,NS,A and HA.Conclusion Hydrogen-rich saline can attenuate global cerebral I/R injury throngh inhibiting the mPTP opening and reducing the dissipation of MMP,thus maintaining the mitochondrial function.

Objective To compare effectiveness,performance,and complications between ultrasound-guided selective cervical nerve root block and interscalene brachial plexus block for patients undergoing arthroscopic surgery in perioperative period.Methods Seventy patients scheduled for arthroscopic surgery,25 males and 45 females,aged 18-75 years,were randomly divided into two groups.They were given either selective cervical nerve root block (group S,n =35) or interscalene brachial plexus block (group ISB,n=35).In group S,C5 and C6 nerve roots were given 0.5％ ropivacaine 5 ml respectively;In group ISB,patients were given 0.5％ ropivacaine 10 ml under ultrasound guidance.The primary outcome:VAS score and forearm modified Bromage scale (MBS) score were recorded at 4,12 and 24 hours after surgery;Secondary outcomes:cumulative tramadol consumption,the patients' satisfaction rate and adverse effects were recorded.Results The VAS scores in group S was significantly lower than that in group ISB at 12 hours after surgery (1.7±0.8 vs 3.6±0.7,P＜0.05).The forearm MBS scores in group S was significantly higher than that in group ISB 4 hours after surgery (P＜0.01).Compared with group ISB,the amount of tramadol consumption was lower at 24 hours after surgery [(37.5±35.9) mg vs (112.5±43.5) mg,P＜0.05)].The satisfaction rate of group S was higher than group ISB (88％ vs 56％,P＜0.05).There was no significant difference in side effects between the two groups.Conclusion In arthroscopic surgery,the selective cervical nerve root block is superior to the brachial plexus block.

To determine the efficacy and safety of selinexor combined with venetoclax (VEN) and azactitidine (AZA) for patients with relapsed and/or refractory acute myeloid leukemia (R/R AML) . Twelve patients with R/R AML treated with selinexor plus VEN and AZA in the Affiliated Cancer Hospital of Zhengzhou University from May 2022 to May 2023 were included. Their clinical data were retrospectively analyzed. Among the 12 R/R AML patients, 5 (41.7%) achieved complete remission (CR) , 1 (8.3%) achieved CR with incomplete hematological recovery, and 5 (41.7%) achieved partial remission. The median time to reach CR was 28 (16-59) days. The median PFS was 61 (15-300) days. The main adverse event of the regimen was hematological toxicity. No chemotherapy-related deaths were observed. The combination of selinexor plus VEN and AZA is an effective treatment for R/R AML patients.