Objective:To evaluate the interaction between remimazolam and propofol for sedation during hysteroscopy.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 20-45 yr, with body mass index of 18-28 kg/m 2, scheduled for elective hysteroscopy, were included. The test was conducted in two steps. Up-and-down sequential allocation was used to determine the median effective dose (ED 50) of remimazolam (group A) and propofol (group B). The ED 50 obtained in A and B groups were then used as the standard to determine the combination regimen in group C (0.25×ED 50 of remimazolam+ 0.75×ED 50 of propofol as the initial dose), in group D (0.5×ED 50 of remimazolam+ 0.5×ED 50 of propofol as the initial dose), and in group E (0.75×ED 50 of remimazolam+ 0.25×ED 50 of propofol as the initial dose). Up-and-down sequential allocation was used to determine the ED 50 of propofol when propofol and remimazolam were combined in C, D and E groups. The interaction between the sedative effects of two drugs was analyzed using the isobolographic analysis method, and the interaction coefficient and synergistic dose ratio of two drugs were calculated. Results:The ED 50 of remimazolam was 0.180 mg/kg in group A, and the ED 50 of propofol was 1.167 mg/kg in group B. The results of isobolographic analysis showed that remimazolam and propofol had a synergistic effect. When remimazolam 0.045, 0.090 and 0.135 mg/kg were combined with propofol 0.546, 0.288 and 0.160 mg/kg, the interaction coefficients were 1.393, 1.339 and 1.127 respectively. The synergistic dosage ratio of remimazolam and propofol was 1.0∶(3.2 to 12.0). Conclusions:Remimazolam and propofol have a synergistic effect on sedation when used for hysteroscopy, and the dose ratio is 1.0∶(3.2-12.0).

Objective:To evaluate the efficacy of esketamine combined with different doses of remimazolam for induction of general anesthesia in pediatric patients.Methods:One hundred and sixty pediatric patients of either sex, aged 3-6 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with body mass index of 13-20 kg/m 2, undergoing elective general anesthesia under a laryngeal mask, were divided into 4 groups ( n=40 each) by the random number table method: esketamine combined with propofol group (KP group) and esketamine combined with different doses of remimazolam group (0.2, 0.3, 0.4 mg/kg) groups (KR1 group, KR2 group, KR3 group). Esketamine 0.8 mg/kg was intravenously injected in the preanesthesia room. After entering the operating room, propofol 2.5 mg/kg was intravenously injected in KP group, and remimazolam 0.2, 0.3 and 0.4 mg/kg were intravenously injected in KR1, KR2 and KR3 groups, respectively. When the child lost consciousness and the Modified Observer′s Assessment of Alertness/Sedation Scale score<1, sufentanil and mevacurium were intravenously injected. When the Modified Observer′s Assessment of Alertness/Sedation Scale score≥1, rescue sedation was performed, and 3 min later the laryngeal mask airway was inserted. The onset time of sedation, response to laryngeal mask airway placement, rescue sedation, hypotension, tachycardia, bradycardia, bucking, hiccup, injection pain and apnea were recorded, and the increase rate of perfusion index (PI) was calculated. Results:No response to laryngeal mask implantation occurred in the four groups. Compared with KP group, the onset time of sedation was significantly prolonged, the incidence of hypotension, bradycardia, injection pain and apnea was decreased, the incidence of tachycardia was increased, and the increase rate of PI was decreased in KR1, KR2 and KR3 groups, and the rate of rescue sedation and incidence of bucking were increased in KR1 and KR2 groups ( P<0.05). Compared with KR1 group, the onset time of sedation was significantly shortened in KR2 group and KR3 group, and the rate of rescue sedation and incidence of bucking were decreased in KR3 group ( P<0.05). Compared with KR2 group, the onset time of sedation was significantly shortened, and the rate of rescue sedation was decreased in KR3 group ( P<0.05). There was no significant difference in the increase rate of PI, hypotension, bradycardia, tachycardia, injection pain and apnea among KR1, KR2 and KR3 groups ( P>0.05). There was no significant difference in the incidence of hiccup among the four groups ( P>0.05). Conclusions:Esketamine 0.8 mg/kg combined with remimazolam 0.4 mg/kg can be safely and effectively used for anesthesia induction and has milder inhibition of respiration and circulation as compared with esketamine combined with propofol in pediatric patients.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

The aim of this study was to investigate the preventive effect of pancreatic duct stent on acute pancreatitis after endoscopic retrograde cholangiopancreatography. A retrospective analysis of the case data of patients who first underwent endoscopic retrograde cholangiopancreatography for choledocholithiasis in the Beijing Friendship Hospital from January 2015 to December 2019 for 5 years. According to whether the pancreatic duct stent was indwelled during the operation, they were divided into pancreatic duct stent group (147 cases) and non-indwelling pancreatic duct stent group (192 cases). The incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography was compared between the two groups according to COTTON criteria. Independent sample t test, Pearson Chi-square test (χ 2) and Fisher′s exact test were used to compare groups′ differences. There were 2 cases of acute pancreatitis in the pancreatic duct stent group, all of which improved after 48 hours. There were 22 cases of acute pancreatitis in the non-indwelling pancreatic duct stent group, of which 20 cases improved within 48 hours, and the other 2 cases had severe pancreatitis, which improved and discharged after 30 days of treatment. There was significant difference in the incidence of acute pancreatitis between the pancreatic duct stenting group (1.4%) and the group without placement of pancreatic duct stents (11.5%) (χ2=12.905, P<0.001). In conclusion, Pancreatic duct stent may be an effective method to prevent PEP.

The aim of this study was to investigate the preventive effect of pancreatic duct stent on acute pancreatitis after endoscopic retrograde cholangiopancreatography. A retrospective analysis of the case data of patients who first underwent endoscopic retrograde cholangiopancreatography for choledocholithiasis in the Beijing Friendship Hospital from January 2015 to December 2019 for 5 years. According to whether the pancreatic duct stent was indwelled during the operation, they were divided into pancreatic duct stent group (147 cases) and non-indwelling pancreatic duct stent group (192 cases). The incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography was compared between the two groups according to COTTON criteria. Independent sample t test, Pearson Chi-square test (χ 2) and Fisher′s exact test were used to compare groups′ differences. There were 2 cases of acute pancreatitis in the pancreatic duct stent group, all of which improved after 48 hours. There were 22 cases of acute pancreatitis in the non-indwelling pancreatic duct stent group, of which 20 cases improved within 48 hours, and the other 2 cases had severe pancreatitis, which improved and discharged after 30 days of treatment. There was significant difference in the incidence of acute pancreatitis between the pancreatic duct stenting group (1.4%) and the group without placement of pancreatic duct stents (11.5%) (χ2=12.905, P<0.001). In conclusion, Pancreatic duct stent may be an effective method to prevent PEP.

Objective:To investigate the urodynamic characteristics in Parkinson's disease(PD)versus multiple system atrophy(MSA)patients with lower urinary tract symptoms(LUTS).Methods:We performed a retrospective study in PD and MSA patients admitted to the First Affiliated Hospital of Zhengzhou University and undergone urodynamic examinations from January 2016 to June 2019.A total of 178 patients, mean age(59.2±9.7)years were enrolled, with 64 PD patients, 74 MSA patients and 40 normal controls.Urodynamic parameters included maximum flow rate(Qmax), post-voided residual urine volume(PVR), bladder compliance(BC), overactive bladder(OAB), maximum cystometric capacity(MCC)and detrusor pressure at maximum flow rate(PdetQmax). Bladder function was assessed.Results:Frequent urination(68.8%)was the most common LUTS in PD patients, as opposed to urinary retention(91.9%)in MSA patients.The Qmax, PdetQmax and incidence of OAB were higher and the PVR were lower in PD patients than in MSA patients [free-flow(FF)-Qmax: (13.5±7.1)ml/s vs.(10.1±5.2)ml/s, U=26.98, P<0.01]; pressure-flow study(PFS)-Qmax: [(13.6±5.7)ml/s vs.(10.5±3.3)ml/s, U=34.90, P<0.01]; PFS-PdetQmax: [(23.9±11.3)cm H 2O vs.(16.3±8.6)cmH 2O, U=35.04, P<0.01]; OAB: (46.9% vs.27.0%, χ2=5.85, P<0.01); FF-PVR: [(30.4±20.0)ml vs.(161.7±79.8)ml, U=-71.81, P<0.01]; PFS-PVR: [(65.9±30.7)ml vs.(212.6±83.0)ml, U=-65.29, P<0.01]. Compared with the control group, the incidences of OAB and PFS-PVR were increased and the MCC and PdetQmax were decreased in the PD group(OAB: 46.9% vs.7.5%, χ2=6.15, P<0.018); PFS-PVR: [(65.9±30.7)ml vs.(22.2±10.4)ml, U=47.25, P<0.01]; MCC: [(305.1±79.7)ml vs.(389.6±65.2)ml, U=-52.13, P<0.01]; PdetQmax: [(23.9±11.3)cmH 2O vs.(37.3±10.3)cmH 2O, U=-49.88, P<0.01]. Compared also with the control group, the MSA group had a lower Qmax, PdetQmax and MCC, FF-Qmax: [(10.1±5.2)ml/s vs.(16.3±4.7)ml/s, U=-50.11, P<0.01]; PFS-Qmax: [(10.5±3.3)ml/s vs.(13.1±5.0)ml/s, U=-27.54, P<0.05]; PdetQmax: [(16.3±8.6)cmH 2O vs.(37.3±10.3)cmH 2O, U=-84.92, P<0.01]; MCC: [(284.3±71.8)ml vs.(389.6±65.2)ml, U=-39.31, P<0.01], a higher PVR, lower bladder compliance(BC)and a higher incidence of OAB(FF-PVR: [(161.7±79.8)ml vs.(22.0±13.0)ml, U=84.82, P<0.01]; PFS-PVR: [(212.6±83.0)ml vs.(22.2±10.4)ml, U=112.54, P<0.01]; BC: (28.4% vs.7.5%, χ2=6.81, P<0.01); OAB: (27.0% vs.7.5%, χ2=17.62, P<0.01). Conclusions:PD and MSA patients with LUTS have bladder dysfunction.MSA patients have more serious bladder dysfunction than PD patients.

Objective: To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation. Methods: Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described. Results: In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079% (769 doses), with the highest incidence of 1.182% (177/14 973) in 5-11 month group and the lowest incidence of 0.849% (18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047% (746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404% (288 doses) and 0.554% (395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281% (522 doses) and 0.810% (247 doses). Also, the incidences of ARs were 0.091% (37 doses) and 0.043% (13 doses) in local, and 1.168% (476 doses) and 0.760% (232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016% (414 doses) and 0.698% (213 doses) in the first and second dose, respectively. Conclusion The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.

Objective: To explore the treatment effect of pedicled myocutaneous island flap of anterolateral thigh muscle on the suprapubic defect caused by bladder exstrophy in children. Methods: The clinical data of 3 adolescents with bladder exstrophy were analyzed. All 3 cases underwent one-stage Kelly procedure and received the treatment using pedicled myocutaneous island flap of anterolateral thigh muscle to repair the suprapubic defect. The bladder expansion was performed with ileal sarcoplasmic layer graft, and the Cohen ureteral reimplantation was performed as well, for 1 case 1, 1 year after the first operation. The others 2 patients didn′t receive the second operation. Results: All operations were successful. The femoral donor regions were directly closed. Postoperative follow-up period was 1-7 years. The myocutaneous island flaps were survived and grew well. All incisions of the femoral donor region were primary healing without scar hypertrophy. Urinary continence was achieved in 2 cases, and partially achieved in 1 case. Recurrent urinary tract infection, recurrent fever or abdominal pain were not observed in all patients. Conclusions The pedicled anterolateral thigh myocutaneous island flap is an alternative way to repair suprapubic defect caused by bladder exstrophy.