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.

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Effects of different types of bone cement augmentation of pedicle screws on prognosis of osteoporotic thoraco-lumbar fractures in elderly patients / 局解手术学杂志

Objective To compare the effects of different types of bone cement augmentation of pedicle screws on the prognosis of osteo -porotic thoracolumbar fractures in elderly patients.Methods From August 2013 to November 2016,184 elderly patients with osteoporotic thoracolumbar fractures in our hospital were selected as the research object,all the patients were randomly divided into observation group and control group,94 cases in each group.Two groups were treated with pedicle screw fixation,the control group received conventional pedicle screw combined with PMMA bone cement augmentation,and the observation group were treated by cannulated pedicle screws combined with PMMA bone cement augmentation,the prognosis of the two groups were recorded.Results All patients were successfully completed the oper-ation without serious complications occurred.There was no significant difference in operation time,intraoperative blood loss,the amount of sin-gle vertebral bone cement,hospitalization time between the two groups(P>0.05).The postoperative 1 month incidence rate of cerebrospinal fluid leakage,bone cement leakage,wound infection,loosening of internal fixation was 4.3% in the observation group,which was lower than 21.3%in the control group,the difference was significant(P<0.05).The postoperative 1 month of vertebral height in the observation group and the control group were respectively(4.53 ±1.11)mm and(5.09 ±1.42)mm that were lower than the preoperative(6.41 ±1.39)mm and(6.38 ±1.31)mm(P<0.05),meanwhile the vertebral height at postoperative 1 month of the observation group was lower than that of the control group,the differences were significant(P<0.05).There were 0 case of Frankle grade A,0 case of grade B,10 cases of grade C, 18 cases of grade D,66 cases of grade E in the observation group at postoperative 1 month,and there were 6 cases,14 cases,20 cases,20 ca-ses and 34 cases of corresponding Frankle grade in the control group,the observation group was significantly better than the control group,the differences were significant(P<0.05).Conclusion The application of cannulated pedicle screw combined with PMMA bone cement in the osteoporotic thoracolumbar fractures does not increase the difficulty of operation,and it can reduce the complications and reduce vertebral height,which is conducive to the recovery of nerve function.