Effect of circLPAR3 on radiosensitivity of esophageal cancer cells by targeting miR-1238 / 中华放射肿瘤学杂志

Objective:To evaluate the effect of circLPAR3 on the radiosensitivity of esophageal cancer cells and investigate its mechanism.Methods:The cancer tissues and and adjacent tissues of 37 patients with esophageal cancer were collected, and esophageal cancer cell lines Eca-109, EC9706 and KYSE30 and esophageal epithelial cells HET-1A were cultured in vitro. The expression levels of circLPAR3 and miR-1238 in the tissues and cells were measured by RT-qPCR. Eca-109 cells were transfected with circLPAR3 siRNA and miR-1238 mimics or co-transfected with circLPAR3 siRNA and miR-1238 inhibitor. Cell cloning experiment was conducted to evaluate the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 on the radiosensitivity of Eca-109 cells. After Eca-109 cells that silenced circLPAR3, overexpressed miR-1238 or silenced both circLPAR3 and miR-1238 were exposed to 4 Gy irradiation, CCK-8 assay (A value), flow cytometry and Western blot were employed to assess the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 combined with 4 Gy irradiation on the proliferation and apoptosis of Eca-109 cells and the expression levels of CyclinD1, p21, Bcl-2 and Bax proteins. Dual luciferase reporter gene experiment and RNA pull down experiment were performed to verify the regulatory relationship between circLPAR3 and miR-1238. Results:Compared with adjacent tissues, the expression level of circLPAR3 was up-regulated in the esophageal cancer tissues ( P<0.05), while that of miR-1238 was down-regulated ( P<0.05). Compared with HET-1A cells, the expression levels of circLPAR3 were up-regulated in the esophageal cancer cell lines Eca-109, EC9706 and KYSE30(all P<0.05), whereas those of miR-1238 were down-regulated (all P<0.05). Silencing circLPAR3 or overexpressing miR-1238 reduced the survival fraction of Eca-109 cells (all P<0.05), and the sensitization ratio was 1.21 and 1.75, respectively. Silencing circLPAR3 or overexpressing miR-1238 decreased the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins (all P<0.05), while increased the apoptosis rate of Eca-109 cells and the expression levels of p21 and Bax proteins (all P<0.05). After silencing circLPAR3 or overexpressing miR-1238 combined with 4 Gy irradiation, the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins were decreased (all P<0.05), while Eca-109 cell apoptosis rate and the expression levels of p21 and Bax proteins were increased (all P<0.05). circLPAR3 targeted and negatively regulated the expression level of miR-1238 in Eca-109 cells. After silencing miR-1238 and circLPAR3 simultaneously, the survival fraction of Eca-109 cells was higher than that when only silencing circLPAR3, and the sensitization ratio was 0.59. Silencing miR-1238 reversed the effects of silencing circLPAR3 combined with 4 Gy irradiation on the proliferation and apoptosis of Eca-109 cells. Conclusion:circLPAR3 is highly expressed in esophageal cancer tissues and cell lines, and silencing the expression of circLPAR3 can inhibit the proliferation of esophageal cancer Eca-109 cells, promote their apoptosis, and enhance cell radiosensitivity by up-regulating miR-1238.

Effect of circ-SFMBT2 on the biological behavior of non-small cell lung cancer cells by targeting the miR-7-5p/ADAM10 axis / 中华医学遗传学杂志

OBJECTIVE@#To explore the effect of circ-SFMBT2 on the biological behavior of non-small cell lung cancer (NSCLC) cells and its regulatory role on the miR-7-5p/ADAM10 axis.@*METHODS@#qRT-PCR and Western blotting were used to determine the expression of circ-SFMBT2, miR-7-5p, and ADAM10 in NSCLC tissues and adjacent tissues. Pearson analysis was used to analyze the correlation between circ-SFMBT2 and miR-7-5p, and between miR-7-5p and ADAM10. In vitro cultured human bronchial epithelial-like cells (HBE) and lung cancer cell lines H1650, H460, A549, H1299. CCK-8 and EdU methods were used to assess the ability of cell proliferation. Plate experiment was used to detect the clone formation ability. Flow cytometry was used to detect the apoptosis rate. Transwell experiment was used to detect cell invasion ability. Dual luciferase reporter experiment detects the targeting relationship between circ-SFMBT2 and miR-7-5p, and between miR-7-5p and ADAM10. Transplanted tumor experiment in nude mice assessed the effect of knocking down circ-SFMBT2 on the growth of transplanted tumor. Immunohistochemical experiments were performed to detect the positive rates of ADAM10 and Ki67 proteins in transplanted tumor tissues.@*RESULTS@#The expression levels of circ-SFMBT2 and ADAM10 were increased in NSCLC tissues and cell lines, while decreased the expression of miR-7-5p. circ-SFMBT2 was negatively correlated with miR-7-5p, while miR-7-5p was negatively correlated with ADAM10. Silencing the overexpression of circ-SFMBT2 and miR-7-5p could inhibit cell proliferation, clone formation and invasion, and also promote apoptosis. circ-SFMBT2 could target miR-7-5p, and ADAM10 was the target gene of miR-7-5p. The combined effect of silencing circ-SFMBT2 and inhibition of miR-7-5p, as well as miR-7-5p overexpression and ADAM10 overexpression could promote cell proliferation, clone formation and invasion, and also suppress cell apoptosis. Silencing circ-SFMBT2 could inhibit the growth of transplanted tumors.@*CONCLUSION@#Silencing circ-SFMBT2 can suppress the proliferation, clone formation, invasion ability and induce apoptosis of NSCLC cells by regulating the miR-7-5p/ADAM10 axis.

Novel oxazine fluorescent dyes for intraoperative neuroimaging / 中国药科大学学报

@#Nerve-specific fluorescent agents can be used as nerve markers in animals to guide surgical procedures and reduce the incidence of intraoperative nerve injury.In this study, the structure of oxazine mother nucleus was modified.A series of oxazine derivative fluorescent dyes YQN-3-YQN-6 were obtained by mass spectrometry and 1H NMR, which can highlight the peripheral nerve structure of rats.Among a series of targeted fluorescent dyes, YQN-3 had emission peaks near NIR and showed highly specific nerve targeting signals in the brachial plexus and sciatic nerves 4 h after intravenous administration.In addition, YQN-3 can accurately locate and identify recurrent laryngeal nerves during thyroidectomy, thus preserving the integrity of these nerves during surgery.With its simple synthesis and low toxicity, YQW-3 can be potentially applied for clinical neural tissue imaging.

The effects of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors / 中华物理医学与康复杂志

Objective:To observe any effect of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors.Methods:The walking of twenty-five stroke survivors was quantified using a gait analysis system. They walked barefoot, wearing a half palm ankle-foot orthosis and wearing a hollow-heel ankle-foot orthosis. Walking speed, step frequency, duration of the swing phase on the healthy and affected sides, risk of falling and Timed Up and Go (TUG) test times were recorded and analyzed.Results:The average gait frequency when wearing the hollow-heel ankle-foot orthosis was significantly faster than that in the other two conditions. The gait asymmetry coefficient was significantly different when the subjects wore the hollow-heel ankle-foot orthosis compared with walking barefoot. Compared with being barefoot, the average TUG time was significantly shorter when wearing either orthosis and the risk of falling was significantly less. The fall risk was significantly lower when wearing the hollow-heel orthosis compared to the half palm orthosis.Conclusion:Wearing either ankle-foot orthosis can significantly correct the gait of stroke survivors and lower their risk of falling, with better effect when wearing the hollow-heel ankle-foot orthosis.

Relationship between long-term learning and memory impairment induced by sevoflurane anesthesia and PSD-95/Kalirin-7/Rac1 signaling pathway in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the relationship between long-term learning and memory impairment induced by sevoflurane anesthesia and postsynaptic density protein-95 (PSD-95)/Kalirin-7/Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling pathway in neonatal rats.Methods:Sixty SPF male Wistar rats, aged 7 days, weighing 12-18 g, were divided into 5 groups ( n=12 each) using a random number table method: control group (group C), 1% sevoflurane anesthesia for 2 h group (group S 1), 1% sevoflurane anesthesia for 4 h group (group S 2), 2% sevoflurane anesthesia for 2 h group (group S 3) and 2% sevoflurane anesthesia for 4 h group (group S 4). Morris water maze test was performed at 4, 8 and 12 weeks after anesthesia.The rats were sacrificed after the last Morris water maze test, and the hippocampal tissues were obtained for microscopic examination of the pathological changes (using HE staining), neuron apoptosis (by TUNEL staining), and expression of PSD-95, Kalirin-7 and Rac1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The apoptosis rate was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the time of stay in the target quadrant was shortened, and the apoptosis rate of hippocampal neurons was increased at 4th, 8th and 12th weeks after anesthesia, phosphorylated Rac1/Rac1 ratio was decreased, and the expression of PSD-95 and Kalirin-7 protein and mRNA was down-regulated in S 1, S 2, S 3 and S 4 groups ( P<0.05). Compared with group S 4, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of stay in the target quadrant was prolonged, and the apoptosis rate of hippocampal neurons was decreased, phosphorylated Rac1/Rac1 ratio was increased, the expression of PSD-95 and Kalirin-7 protein and mRNA was up-regulated, and the histopathological changes of hippocampal tissues were attenuated in S 1, S 2 and S 3 groups ( P<0.05). Conclusions:The mechanism by which sevoflurane anesthesia induces long-term learning and memory impairment may be related to inhibition of activity of PSD-95/Kalirin-7/Rac1 signaling pathway in hippocampi of neonatal rats.

Influence of bionic texture coronary stent on hemodynamics after implantation / 生物医学工程学杂志

To explore the influence of bionic texture coronary stents on hemodynamics, a type of bioabsorbable polylactic acid coronary stents was designed, for which a finite element analysis method was used to carry out simulation analysis on blood flow field after the implantation of bionic texture stents with three different shapes (rectangle, triangle and trapezoid), thus revealing the influence of groove shape and size on hemodynamics, and identifying the optimal solution of bionic texture groove. The results showed that the influence of bionic texture grooves of different shapes and sizes on the lower wall shear stress region had a certain regularity. Specifically, the improvement effect of grooves above 0.06 mm on blood flow characteristics was poor, and the effect of grooves below 0.06 mm was good. Furthermore, the smaller the size is, the better the improvement effect is, and the 0.02 mm triangular groove had the best improvement effect. Based on the results of this study, it is expected that bionic texture stents have provided a new method for reducing in-stent restenosis.

Efficacy of sugammadex for reversal of residual neuromuscular blockade after laparoscopic radical gastrectomy in elderly patients / 中华麻醉学杂志

Objective:To evaluate the efficacy of sugammadex for the reversal of residual neuromuscular blockade after laparoscopic radical gastrectomy in elderly patients.Methods:Sixty patients of both sexes, aged 65-85 yr, with body mass index of 20-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic radical gastrectomy under general anesthesia, were divided into 2 groups ( n=30 each) by a random number table method: sugammadex group (S group) and neostigmine group (N group). Rocuronium 0.3-0.6 mg·kg -1·h -1 was intravenously infused during operation, and the muscle relaxation was monitored by a Veryark-TOF monitor, maintaining TOF ratio=0 and counting 1 or 2 after tonic stimulation.Rocuronium was discontinued when the peritoneum was closed.The patients were admitted to the PACU after operation.When the muscle relaxation monitoring T 2 appeared, sugammadex 2 mg/kg was intravenously injected in S group, and neostigmine 0.03 mg/kg plus atropine 0.015 mg/kg was intravenously injected in N group.The tracheal tube was removed after the patient′s consciousness and spontaneous breathing recovered.Before anesthesia (T 1) and 5 and 30 min after tracheal extubation (T 2, 3), arterial blood samples were collected for blood gas analysis, PaO 2 and PaCO 2 were recorded, and ultrasound was used to measure the diaphragm end-inspiratory thickness, end-expiratory thickness and mobility of diaphragm muscle at the above time points.The diaphragm thickening fraction was calculated.The time of T 2 appeared, time of extubation, time of postanesthesia care unit (PACU) stay, postoperative hospital stay, and residual neuromuscular blockade (TOF ratio <0.9) and hypoxemia occurred within 30 min after extubation were recorded.The pulmonary complications within 7 days after operation were recorded. Results:Compared with group N, PaO 2 was significantly increased and PaCO 2 was decreased at T 2, 3, the mobility of diaphragm muscle and diaphragm thickening fraction were increased at T 2, the tracheal extubation time, time of PACU stay and postoperative hospital stay were shortened, the residual neuromuscular blockade and hypoxemia occurred after extubation and incidence of pulmonary complications after operation were decreased ( P<0.05), and no significant change was found in the time of T 2 appeared in group S ( P>0.05). Conclusion:Sugammadex can quickly and effectively reverse the residual neuromuscular blockade after laparoscopic radical gastrectomy, which is helpful for early postoperative recovery in elderly patients.

Improvement of preoperative interview in patients undergoing resection of tumor: the efficacy of humanistic care / 中华麻醉学杂志

Objective:To evaluate the efficacy of preoperative interview with humanistic care in patients undergoing resection of tumor.Methods:Two hundred patients, aged 35-64 yr, with body mass index of 18-28 kg/m 2, of American Society Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective laparoscopic gastrointestinal tumor resection, were divided into 2 groups ( n=100 each) by a random number table method: conventional preoperative interview group (group C) and preoperative interview with humanistic care group (group H). Pre-interview anxiety was assessed using the Self-Rating Anxiety Scale (SAS) at 1 day before the interview (T 0), and pre-interview heart rate (HR) and mean arterial pressure (MAP) were recorded, followed by a preoperative interview.Conventional preoperative interview was given in group C, and preoperative interview with humanistic care was given in group H. Anxiety was assessed again after interview (T 1) and HR and MAP were recorded at 24 h. Venous blood samples were collected for determination of plasma norepinephrine (NE) and cortisol (Cor) concentrations by enzyme-linked immunosorbent assay at T 0 and T 1. Results:Compared with group C, the MAP, HR and SAS scores were significantly decreased at T 1, the incidence and degree of anxiety and plasma NE and Cor concentrations were decreased at T 1, and the incidence of abnormalities of MAP, HR and plasma Cor concentrations were decreased in group H ( P<0.05). Conclusion:Preoperative interview with humanistic care can alleviate the post-interview anxiety and reduce the over-stress response in patients undergoing resection of tumor.

Effect of remimazolam pretreatment on brain injury following thalamic hemorrhage in mice / 中华麻醉学杂志

Objective:To evaluate the effect of remimazolam pretreatment on brain injury following thalamic hemorrhage in mice.Methods:Sixty clean-grade healthy adult CD1 male mice, weighing 25-30 g, aged 7-8 weeks, were divided into 3 groups ( n=20 each) by using a random number table method: sham operation group (Sham group), brain injury group (BI group) and remimazolam pretreatment group (Rem group). Remimazolam 25 mg/kg was intravenously injected via the tail vein in group Rem.and the equal volume of normal saline was given instead in Sham group and BI group.Ten min later, type Ⅳ collagenase 0.01 U/10 nl was microinjected into unilateral ventroposterolateral nucleus and ventromedial nucleus to develop a mouse model of brain jury induced by thalamic hemorrhage.The rats were sacrificed at 6 h after developing the model, brain tissues were taken for measurement of the wet/dry weight (W/D) ratio, and hippocampal tissues were taken and stained with haematoxylin and eosin for determination of the count of the viable neurons in the hippocampal dentategyrus area, count of apoptotic neurons in the hippocampal CA1 region (by TUNEL), expression of CCAAT/enhancer-binding protein homologous protein (CHOP), activating transcription factor 4 (ATF4) and X-box binding protein-1 (XBP1) mRNA (by real-time polymerase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot) and for microscopic examination of ultrastructure of hippocampal tissues (with a transmission electron microscope). Results:Compared with group Sham, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly increased, the count of viable neurons in the hippocampal dentate gyrus was decreased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was up-regulated, the expression of CHOP, caspase-3 and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in BI and Rem groups ( P<0.05). Compared with group BI, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly decreased, the number of viable neurons in the hippocampal dentate gyrus was increased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was down-regulated, the expression of CHOP, caspase-3 and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group Rem ( P<0.05). Conclusion:Remimazolam pretreatment can reduce the brain injury following thalamic hemorrhage in mice, and the mechanism may be related to inhibition of cell apoptosis induced by endoplasmic reticulum stress in hippocampus.

Effects of Dexmedetomidine on Postoperative Delirium in Liver Tumor Resection Elderly Patients with Sleep Disorders / 中国药房

OBJECTIVE：To investigate the effects of d exmedetomidine on postoperative delirium （POD） in liver tumor resection elderly patients with sleep disorder （SD）. METHODS ：Totally 80 patients undergoing liver tumor resection with preoperative Pittsburgh sleep quality index （PSQI）score ≥7 were selected from the Affiliated Cancer Hospital of Zhengzhou University from Jan. 1st，2020 to Oct. 31st，2020. They were randomly divided into group SD and group Dex according random number table ，with 40 cases in each group. At the same time ，40 patients with preoperative PSQI score ＜7 were selected as group C. Thirty min before anesthesia induction ，Dexmedetomidine hydrochloride injection 0.4 μg/kg was injected intravenously in group Dex. Etomidate emulsion injection ，Sufentanil citrate injection and Rocuronium bromide injection were used for anesthesia induction in 3 groups，and Ropofol medium/long chain fat emulsion injection + Remifentanil hydrochloride for injection was used to maintain anesthesia. The drug use ，operation time ，PACU stay time and postoperative hospital stay were recorded in 3 groups. The cognitive function was evaluated 2 h before operation and 1，3，5，7 days after operation. The occurrence of POD was observed. The plasma levels of IL- 6 and S 100β were measured 2 h before operation ，2 h after operation ，1，3，5 days after operation. The occurrence of ADR was recorded. RESULTS ：There was no statisti cal significance in intraoperativ e drug use and operation time among 3 groups （P＞0.05）. The PACU stay time ， the incidence of POD and the duration of POD in group SD an d lixxi18@126.com group Dex were significantly higher or longer than group C ， while the Dex group was significantly lower or shorter thangroup SD （P＜0.05）. The postoperative hospitalization stay ofgroup SD was significantly longer than group C and group Dex （P＜0.05），and there was no statistical significance between group Dex and group C （P＞0.05）. Before operation ，there was no statistical significance in MMSE scores or plasma levels of IL- 6 and S100β among 3 groups（P＞0.05）. MMSE scores of group C 1，3 days after operation ，those of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than those before operation. MMSE scores of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than group C at corresponding period ；the group Dex was significantly higher than the group SD at corresponding period （P＜0.05）. The plasma levels of IL- 6 and S 100 β at different time points were significantly higher than before operation ，and the group SD and group Dex were significantly higher than the group C ，and the group Dex was significantly lower than group SD at corresponding period （P＜0.05）. There was no statistical significance in the total incidence of ADR among 3 groups（P＞0.05）. CONCLUSIONS ：SD can promote the occurrence of POD in liver tumor resection elderly patients. Dexmetomidine can reduce the incidence of POD in elderly patients with preoperative SD ，the mechanism of which may be associated with the inhibition of IL- 6 and S 100β expression and the alleviation of brain injury with good safety.

Comparison of the Effects of Remimazolam and Propofol on Perioperative Cellular Immune Function in Patients underwent Radical Mastectomy / 中国药房

OBJECTIVE：To c ompare the effects o f intravenous anesthesia with remimazolam and propofol on perioperative cellular immune function in patients underwent radical mastectomy. METHODS ：Eighty patients underwent selective radical mastectomy were collected ，and then randomly divided into remimazolam group （group R ）and propofol group （group P ）. During anesthesia induction ，group R was intravenously injected with remimazolam 0.2 mg/kg+sufentanil 0.3 μg/kg+cisatracurium 0.2 mg/kg；group R was intravenously injected with propofol 2 mg/kg+sufentanil 0.3 μg/kg+cisatracurium 0.2 mg/kg. During anesthesia maintenance，group R was intravenously pumped with remimazolam 0.4-1.2 mg/（kg·h）+remifentanil 0.1-0.2 μg（/ kg·min）；group P was intravenously pumped with propofol 4-10 mg/（kg·h）+remifentanil 0.1-0.2 μg（/ kg·min）. Both groups were given intravenous injection of cisatracurium intermittently. The anesthesia depth was monitored during the operation and the pumping speed of remimazolam，propofol and remifentanil was adjusted accordingly. The intraoperative infusion volume ，blood loss ，operation time ， opioid dosage ，and visual analogue scale （VAS）scores at 24 and 72 hours after operation were recorded in 2 groups；at the same time，the levels of T lymphocyte CD 3+，CD4+，CD8+ and NK cells were measured 30 min before anesthesia induction ，24 h and 72 h after operation ；CD4+/CD8+ was also calculated. The incidence of ADR was recorded in 2 groups. RESULTS ：There was no statistical significance in intraoperative infusion volume ，blood loss ，operation time ，opioid dosage ，VAS score at 24，72 hours after operation and the incidence of ADR between 2 groups（P＞0.05）. Compared with 30 min before anesthesia induction ，the levels of CD 3+，CD4+，NK cells and CD 4+/CD8+ ratio in 2 groups at 24 hours after operation were significantly decreased （P＜ 0.05）；compared with group P ，the levels of CD 3+，CD4+ and NK cells as well as CD 4+/CD8+ ratio in group R increased significantly in group R （P＜0.05）. CONCLUSIONS ：For anesthesia maintenance ，the inhibitory effects of remimazolam on perioperative cellular immunity in patients underwent radical mastectomy are poorer than propofol.

circ-PRKDC affects the proliferation, apoptosis and radiosensitivity of lung cancer cells by regulating miR-505-3p / 中华放射肿瘤学杂志

Objective:To investigate the effect of circ-PRKDC on lung cancer cell proliferation, apoptosis and radiosensitivity and its molecular mechanism.Methods:Normal lung epithelial cells BEAS-2B and lung cancer cell lines NCI-H1299, NCI-H2170, NCI-H1975 were cultured. NCI-H1299 cells were divided into the si-NC, si-PRKDC, pcDNA-NC, pcDNA-PRKDC, miR-NC, miR-505-3p, anti-miR-NC, anti-miR-505-3p, si-PRKDC+ anti-miR-NC and si-PRKDC+ anti-miR-505-3p groups. RT-qPCR was used to detect the expression levels of circ-PRKDC and miR-505-3p. Western blot was employed to measure the protein expression. MTT was used to detect cell proliferation. Flow cytometry was utilized to detect cell apoptosis. Plate clone formation assay was conducted to detect the cell radiosensitivity. Dual luciferase reporter assay was performed to analyze the targeting relationship between circ-PRKDC and miR-505-3p.Results:Compared with normal lung epithelial cells BEAS-2B, the expression levels of circ-PRKDC in the lung cancer cell lines NCI-H1299, NCI-H2170 and NCI-H1975 were significantly up-regulated (3.65, 3.10, 2.67 vs. 1.00, all P<0.05), whereas those of miR-505-3p were significantly down-regulated (0.42, 0.50, 0.54 vs. 1.02, all P<0.05). After low expression of circ-PRKDC, the expression level of CyclinD1 was significantly down-regulated (0.42 vs. 0.81, P<0.05), whereas those of Cleaved-caspase-3(0.71 vs. 0.33, P<0.05) and γ-H 2AX (0.89 vs. 0.46, P<0.05) were significantly up-regulated, the cell A value was significantly decreased (0.413 vs. 0.839, P<0.05), cell apoptosis rate was significantly increased (20.35 vs. 6.21, P<0.05), cell survival fraction was significantly decreased ( P<0.05), and β-catenin expression was significantly down-regulated (0.35 vs. 0.73, P<0.05). After high expression of miR-505-3p, the expression level of CyclinD1 was significantly down-regulated (0.34 vs. 0.83, P<0.05), those of Cleaved-caspase-3(0.65 vs. 0.32, P<0.05) and γ-H 2AX (0.96 vs. 0.45, P<0.05) were significantly up-regulated, the cell A value was significantly decreased (0.386 vs. 0.851, P<0.05), the apoptosis rate was significantly increased (16.38 vs. 6.20, P<0.05), and the cell survival fraction was significantly decreased ( P<0.05). Compared with miR-NC, the luciferase activity of miR-505-3p group transfected with circ-PRKDC wild-type reporter plasmid was significantly decreased (0.44 vs. 1.00, P<0.05). Down-regulation of miR-505-3p could reverse the effect of low expression of circ-PRKDC on the proliferation, apoptosis, radiosensitivity and β-catenin expression of NCI-H1299 cells. Conclusion:Low expression of circ-PRKDC may inhibit lung cancer cell proliferation, promote cell apoptosis and enhance cell radiosensitivity by up-regulating miR-505-3p, which is probably associated with the Wnt/β-catenin signaling pathway.

Effect of PSD-95 on long-term learning and memory impairment in neonatal rats induced by sevoflurane anesthesia / 中华行为医学与脑科学杂志

Objective:To investigate the effect of postsynaptic density-95(PSD-95)on long-term learning and memory impairment in neonatal rats induced by sevoflurane anesthesia.Methods:A total of 54 SD rats aged 7 days of SPF grade were randomly divided into 3 groups: control group (exposed to air), model group (exposed to 2.1% sevoflurane, 4 h/d, consecutive 3 days) and PSD-95 inhibitor group (inhaled sevoflurane+ intraperitoneal injection NA-1, consecutive 5 days), with 18 rats in each group.Morris water maze test and new object recognition test were used to detect the ability of visuospatial learning and memory and recognition memory of rats in each group.RT-qPCR was used to detect the mRNA levels of kalirin, Rac1 and PSD-95 in rat hippocampus.The expressions of kalirin, Rac1, PSD-95 and apoptosis related proteins Caspase-3, Bcl-2 and Bax in rat hippocampus were detected by Western blot.The expression levels of kalirin and Rac1 in hippocampus were detected by immunohistochemistry.SPSS 23.0 software was used for statistical analysis.Repeated measurement ANOVA and one-way ANOVA was used for comparing among groups.Results:Repeated measurement ANOVA showed that in the water maze test, the interaction between time and group of platform seeking latency and swimming distance of the three groups were significant ( Ftime×group=36.539, 41.548, both P<0.01). Simple effect analysis showed that the platform latency and swimming distance in the model group from day 2 to 6 were longer than those in the control group (platform latency from day 2 to 6: t=14.039, 17.147, 13.155, 13.831, 27.247, all P<0.01; swimming distance from day 2 to 6: t=10.122, 20.987, 7.267, 10.011, 8.121, all P<0.01). Compared with the model group, from day 2 to 6, the platform latencies of PSD-95 inhibitor group were prolonged( t=7.948, 14.768, 11.582, 12.832, 24.346, all P<0.01) and the swimming distances were increased( t=8.235, 24.325, 11.234, 12.031, 7.036, all P<0.01). The new object recognition test found that the new object exploration time in the model group was significantly longer than that in the control group ((21.30±2.27)s, (19.21±1.42)s, t=1.843, P<0.01), and the new object exploration time in the PSD-95 inhibitor group was significantly longer than that in the model group ((26.83±2.13)s, t=4.844, P<0.01). The difference index of novel objects in the model group was significantly lower than that in the control group ((0.41±0.12), (0.59±0.10), t=3.416, P<0.01), and the difference index of novel objects in the PSD-95 inhibitor group was significantly lower than that in the model group ((0.37±0.08), t=0.696, P<0.05). The qRT-PCR results showed that the expressions of Rac1, kalirin and PSD-95 mRNA in the model group were significantly lower than those in the control group ( t=9.969, 3.954, 6.561, P<0.05), and the expressions of Rac1, kalirin and PSD-95 mRNA in the PSD-95 inhibitor group were significantly lower than those of the model group ( t=2.132, 2.251, 3.502, all P<0.05). Immunohistochemistry results showed that the kalirin in the hippocampus CA1 area of the model group was significantly lower than that in the control group((8.18±1.94) vs (15.47±3.35), t=11.47, P<0.01), and kalirin in the PSD-95 inhibitor group was significantly lower than that in the model group((4.98±1.53), t=10.28, P<0.01); Rac1 in the model group was significantly lower than that in the control group ((3.72±1.53), (8.17±2.91), t=6.76, P<0.01), and the Rac1 in the PSD-95 inhibitor group(2.73±0.37) was significantly lower than the model group ( t=4.72, P<0.05). Western blot results showed that Caspase-3((1.37±0.16) vs (0.54±0.01), t=5.71, P<0.01) and Bax((1.87±0.31) vs (1.23±0.25), t=12.01, P<0.01) protein levels in the model group were significantly higher than those in the control group.Caspase-3 and Bax protein levels in the PSD-95 inhibitor group were significantly higher than those in model group (Caspase-3: (1.79±0.17), t=9.87, P<0.01; Bax: (2.19±0.21), t=16.19, P<0.01). The Bcl-2 protein level in the model group was significantly lower than that of the control group ((1.22±0.21) vs (1.96±0.38), t=11.92, P<0.01). And the Bcl-2 protein level in the PSD-95 inhibitor group (1.01±0.19) was significantly lower than that in the model group ( t=10.73, P<0.01). Conclusion:Sevoflurane anesthesia can damage the long-term learning and memory function and reduce the expression of PSD95 protein in neonatal rats.Inhibiting the expression of PSD95 can aggravate this damage, which may be related to the synaptic plasticity and apoptosis of neurons involved in PSD95.

Optimized anesthesia strategy for thoracic combined with laparoscopic radical resection of esophageal cancer in elderly patients: thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia / 中华麻醉学杂志

Objective:To evaluate the optimized efficacy of thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia for elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ orⅡ patients of both sexes, aged 66-78 yr, weighing 46-80 kg, undergoing elective thoracoscopic combined with laparoscopic radical resection of esophageal cancer, were divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group G) and thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia group (TSG group). Both groups received target-controlled infusion of propofol and remifentanil and intravenous injection of cisatracurium besilate for anesthesia induction and maintenance, with BIS value maintained at 45-60 during operation.Thoracic paravertebral nerve block on the affected side was performed under ultrasound guidance after the end of anesthesia induction, and 0.5% ropivacaine 15 ml was injected in TSG group.The patients were turned to the supine position after the thoracic operation was completed, and the bilateral subcostal approach to the transversus abdominis plane block was performed under ultrasound guidance, and 0.3% ropivacaine 20 ml was injected into each side.Sufentanil was used for patient-controlled intravenous anesthesia (PCIA) after operation.The background infusion rate was 0.05 μg·kg -1·h -1, PCA was 0.04 μg/kg, and the lockout interval was 10 min in group G. The background infusion rate was 0.03 μg·kg -1·h -1, PCA was 0.025 μg/kg, the lockout interval was 10 min in group TSG.Both groups received analgesia until 48 h after operation, and VAS score was maintained ≤3.When VAS score ≥ 4, tramadol 100 mg was intravenously injected for rescue analgesia.At 1 day before operation (T 0), immediately before anesthesia induction (T 1), at 1 h after emergence from anesthesia (T 2), and 4, 8, 12, 24 and 48 h after operation (T 3-7), venous blood samples were collected for determination of serum norepinephrine, epinephrine and cortisol concentrations (by enzyme-linked immunosorbent assay). The intraoperative consumption of remifentanil and occurrence of cardiovascular events were recorded.The pressing times of PCA, consumption of sufentanil and requirement for rescue analgesia within 48 h after operation were recorded.The occurrence of nerve block-related complications (hematoma at the puncture site, infection, local anesthetic poisoning, etc.) and adverse reactions such as nausea and vomiting, respiratory depression and pruritus were recorded within 48 h after the operation. Results:Compared with group G, the concentrations of serum epinephrine, norepinephrine and cortisol were significantly decreased, the consumption of intraoperative remifentanil and postoperative sufentanil and pressing times of PCA were reduced, the rate of rescue analgesia was decreased, scores of satisfaction with analgesia were increased, and the incidence of intraoperative cardiovascular events and postoperative adverse reactions such as nausea and vomiting, pruritus and respiratory depression were decreased in group TSG ( P<0.05). Conclusion:Thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia can reduce the perioperative consumption of opioids and inhibit perioperative stress responses and postoperative hyperalgesia with fewer adverse reactions when used for the elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.

Modified efficacy of thoracic paravertebral block combined with general anesthesia in patients undergoing laparoscopic radical nephrectomy / 中华麻醉学杂志

Objective:To evaluate the modified efficacy of thoracic paravertebral block (TPVB) combined with general anesthesia in the patients undergoing laparoscopic radical nephrectomy.Methods:Eighty patients, aged 38-64 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective laparoscopic radical nephrectomy, were selected and randomly divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group GA) and TPVB combined with general anesthesia group (group TPVB+ GA). A paravertebral catheter was placed at T 8 and T 10 under ultrasound guidance before induction of anesthesia, and 0.5% ropivacaine 10 ml was administered via the catheter in group TPVB+ GA.Anesthesia was induced with propofol, sufentanil, etomidate and rocuronium and maintained by intravenous infusion of propofol and remifentanil.Patient-controlled intravenous analgesia was performed with sufentanil, ketorolac tromethamine and tropisetron at the end of surgery.When postoperative visual analog scale score≥4, tramadol 50 mg was intravenously injected as rescue analgesic.Immediately before anesthesia induction (T 0), at 5 min after establishing pneumoperitoneum (T 1), at 2 h of pneumoperitoneum (T 2), and immediately after the end of pneumoperitoneum (T 3), and at 24 h after operation (T 4), venous blood samples were collected for determination of plasma norepinephrine concentrations (by enzyme-linked immunosorbent assay), plasma cortisol level (using radioimmunoassay), and blood glucose concentrations were measured.The intraoperative consumption of sufentanil and remifentanil was recorded.The intraoperative hypertension, hypotension, and bradycardia were recorded, and the nausea and vomiting, pruritus, and requirement for rescue analgesia occurred within 24 h after surgery were recorded. Results:Compared with group GA, the plasma concentrations of norepinephrine, cortisol and blood glucose were significantly decreased at T 1-4, the intraoperative consumption of sufentanil and remifentanil was reduced, and the postoperative requirement for rescue analgesia was decreased in group TPVB+ GA ( P<0.05). There was no significant difference in the incidence of intraoperative and postoperative adverse reactions between the two groups ( P>0.05). Conclusion:TPVB combined with general anesthesia is helpful in carrying out the anesthetic model of low-consumption opioids and is more helpful in inhibiting intraoperative and postoperative stress responses and postoperative pain responses than general anesthesia alone when used for laparoscopic radical nephrectomy.

Effects of bumetanide on changes of NKCC1 and KCC2 mRNA expression in hypothalamus and anxiety in adulthood induced by multiple sevoflurane exposure in neonatal rats / 中华行为医学与脑科学杂志

Objective:To investigate the effects of bumetanide on changes of NKCC1 and KCC2 mRNA expression in hypothalamus and anxiety in adulthood induced by multiple sevoflurane exposure in neonatal rats.Methods:Eighty-one healthy male Sprague-Dawley rats, at postnatal 5 days (P5), were randomly divided into 3 groups ( n=27 in each group): control group (group C), multiple sevoflurane group (group MS) and bumetanide group (group B). The rats were commonly reared in the cage and received no anesthesia in group C. Animals were exposed to 2.1% sevoflurane for 2 h on P5, P7, P9 in group MS and group B. In group B, animals received intraperitoneal injection of 1.82 mg/kg bumetanide(Na + -K + -2Cl - cotransporter 1 blocker, NKCC1 blocker)at 30 min before every anesthesia.The animals in group C and group MS received the same dose of dimethyl sulfoxide subcutaneously at the same time as group B. The rats were observed for 30 minutes after recovery from anesthesia, and then breastfed normally.On the 9th day after birth, six rats were taken from each group immediately at the end of anesthesia and the blood was collected by left ventricular puncture for blood gas analysis.At 30 min after anesthesia, 6 animals in each group were decapitated and the hypothalamus part of brain tissue was collected.Then the expression level of IL-6 mRNA, NKCC1 mRNA and KCC2 mRNA were detected by RT-PCR.The other rats in each group were raised to 60 days for the elevated plus maze (EPM) test. Results:Compared with group C, the expression of IL-6 mRNA and NKCC1 mRNA in hypothalamus of MS group was up-regulated (IL-6: (1.000±0.207) vs (1.782±0.231); t=6.899, P<0.01; NKCC1: (1.000±0.255) vs (1.639±0.290); t=3.518, P<0.01), the KCC2 mRNA expression was down-regulated ((1.000±0.140) vs (0.733±0.115); t=3.017, P<0.001) and the NKCC1/KCC2 mRNA ratio increased ((1.000±0.276) vs (2.054±0.521); t=5.078, P<0.001) and the differences were statistically significant.Compared with MS group, the expression of IL-6 mRNA and NKCC1 mRNA in hypothalamus of group B was down-regulated (IL-6: (1.147±0.140); t=5.635, P<0.01; NKCC1: (1.038±0.385); t=3.310, P=0.01), KCC2 mRNA expression was up-regulated((0.988±0.194); t=2.880, P<0.05), NKCC1 / KCC2 mRNA ratio was decreased((1.027±0.200); t=4.950, P<0.001), and the differences were statistically significant.EPM behavioral test showed that compared with group C, the open arm residence time in MS group was significantly shorter than that in group C ((18.4±10.1)s vs (4.3±3.1)s; P<0.01); compared with group MS, the open arm residence time in group B was significantly prolonged((16.6±7.6)s, P<0.05). Conclusion:Bumetanide can reduce the up-regulation of NKCC1 level and the down-regulation of KCC2 level in neonatal rats after sevoflurane anesthesia, and alleviate the anxiety state of adult rats.

Effect of sevoflurane preconditioning on HMGB1∕TLR4∕NF-κB signaling pathway during lung ische-mia-reperfusion in rats / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane preconditioning on high-mobility group box 1 protein ( HMGB1) ∕Toll-like receptor 4 ( TLR4) ∕nuclear factor kappa B ( NF-κB) signaling pathway during lung ischemia-reperfusion ( I∕R) in rats. Methods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group ( group S) , lung I∕R group ( group I∕R) and sevoflu-rane preconditioning group ( group SP ) . The right pulmonary hilum was only isolated but not ligated in group S. Lung I∕R was induced by clamping the right pulmonary hilum for 60 min followed by 120 min of reperfusion in anesthetized rats in group I∕R. In group SP, 2. 1％ sevoflurane was inhaled for 30 min to per-form sevoflurane preconditioning, and the lung I∕R model was established at 10 min after the end of inhala-tion. The rats were sacrificed at 120 min of reperfusion, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet to dry weight ratio ( W∕D ratio) , con-tent of tumor necrosis factor-alpha ( TNF-α) in lung tissues ( by enzyme-linked immunosorbent assay) and expression of HMGB1, TLR4 and NF-κB protein in lung tissues (by Western blot). Results Compared with group S, the pathological scores, W∕D ratio and content of TNF-α were significantly increased, and the expression of HMGB1, TLR4 and NF-κB was up-regulated in I∕R and SP groups ( P<0. 05) . Compared with group I∕R, the pathological scores, W∕D ratio and content of TNF-αwere significantly decreased, and the expression of HMGB1, TLR4 and NF-κB was down-regulated ( P<0. 05) , and the pathological changes of lung tissues were significantly attenuated in group SP . Conclusion Sevoflurane preconditioning reduces lung I∕R injury probably through inhibiting HMGB1∕TLR4∕NF-κB signaling pathway in rats.

Effects of OPRM1A118G and CYP3A4*18B genetic polymorphism and the interaction on postoperative analgesia with fentanyl in patients undergoing radical resection of lung cancer / 中华麻醉学杂志

Objective To evaluate the effects of OPRM1All8G and CYP3A4*18B genetic polymorphism and the interaction on postoperative analgesia with fentanyl in the patients undergoing radical resection of lung cancer.Methods One hundred and thirty-nine patients (native of Henan province),aged 40-64 yr,weighing 40-70 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective radical resection of lung cancer under general anesthesia,were enrolled in this study.The polymorphic sites of the OPRM1All8G and CYP3A4*18B allele were analyzed by using polymerase chain reaction technique and ABI 3130 Genetic Analyzer.The patients were divided into wild homozygote group (group AA,group *1/*1),heterozygote group (group AG,group * 1/*18B) and mutation homozygote group (group GG,group *18B/*1SB) according to their genotypes.The patients were divided into 7 groups according to the interaction between the two genes:AA plus *1/*1 group (group Ⅰ),AA plus *1/*18B group (group Ⅱ),AG plus *1/*1 group (group Ⅲ),AG plus *1/*18B group (group Ⅳ),GG plus * 1/*1 group (group Ⅴ),GG plus *1/*18B group (group Ⅵ) and *18B/*18B group (group Ⅶ).Patientcontrolled intravenous analgesia with fentanyl was started at the end of surgery to maintain the visual analogue scale ≤ 3 points.The amount of fentanyl used within 24 and 48 h after surgery was recorded,and the occurrence of adverse reactions within 48 h after surgery was observed.Results The amount of fentanyl used within 24 and 48 h after surgery was significantly higher in group GG than in group AA (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly lower in group *18B/*18B than in group *1/*1 (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly higher in Ⅱ and Ⅳ groups than in group Ⅰ,in group Ⅲ than in group Ⅱ,in group Ⅴ than in Ⅰ-Ⅳ groups,and in group Ⅵ than in Ⅱ and Ⅳ groups,and was significantly lower in group Ⅶ than in Ⅰ-Ⅵ groups (P＜ 0.05).There was no significant difference in the incidence of adverse reactions within 48 h after surgery between groups (P＞0.05).Conclusion OPRM1A1l8G and CYP3A4*18B genetic polymorphism and the interaction are the genetic factors contributing to individual variation in fentanyl pharmacodynamics in the patients undergoing radical resection of lung cancer.

Efficacy of high frequency two-lung ventilation with low tidal volume assisted by CO2 pneumothorax for airway management in patients undergoing thoracoscopic radical resection of esophagus cancer / 中华麻醉学杂志

Objective To evaluate the efficacy of high frequency two-lung ventilation (TLV) with low tidal volume assisted by CO2 pneumothorax for airway management in patients undergoing thoracoscopic radical resection of esophagus cancer.Methods Thirty patients of both sexes,aged 48-64 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective thoracoscopic radical resection of esophagus cancer,were divided into 2 groups (n =15 each) using a random number table:onelung ventilation group (group O) and TLV group (group T).A left-sided double-lumen tube was inserted orally in group O,and a single-lumen tube was placed orally in group T.During thoracoscopic surgery,the left lung was ventilated,with tidal volume 8 ml/kg and respiratory rate 14 breaths/min in group O.In group T,artificial pneumothorax was induced by continuous CO2 insufflation with CO2 pressure at 10 mmHg,and bilateral lungs were ventilated,with tidal volume 5 ml/kg and respiratory rate 20 breaths/min.Mean arterial pressure and heart rate were recorded before induction of anesthesia,immediately after intubation (T1),at 10 min after intubation (T2),at 30 min after the start of thoracoscopic surgery (T3),immediately after the end of thoracoscopic surgery (T4) and at 30 min of TLV (T5).Arterial blood samples were collected for blood gas analysis at T2,T3,T4 and T5.The exposure of the surgical field and the number of lymph node dissection in the left recurrent laryngeal nerve chain were recorded during surgery.The emergence time,extubation time and time for recovery of consciousness were recorded.Results Arterial oxygen partial pressure was significantly lower at T3,4 than at T2 in the two groups,and arterial carbon dioxide partial pressure was significantly higher,and the pH value was lower at T3,4 than at T2 in group T (P＜0.05).Compared with group O,arterial carbon dioxide partial pressure was significantly increased,the pH value was decreased,and the number of lymph node dissection in the left recurrent laryngeal nerve chain was increased at T3,4 in group T (P＜0.05).There were no significant differences between the two groups in the good exposure of the surgical field,emergence time,extubation time and time for recovery of consciousness (P＞0.05).Conclusion High frequency TLV with low tidal volume when assisted by CO2 pneumothorax can serve as a feasible mode for airway management in patients undergoing thoracoscopic radical resection of esophagus cancer.

Effect of OPRM1A118G genetic polymorphism on postoperative analgesia with fentanyl in patients undergoing radical resection of lung cancer / 中华麻醉学杂志

Objective To evaluate the effect of OPRM1A118G genetic polymorphism on postoperative analgesia with fentanyl in the patients undergoing radical resection of lung cancer.Methods One hundred and seventy-four patients(native of He′nan province), aged 40-64 yr, weighing 40-70 kg, with American Society of Anesthesiologists physical status Ⅰor Ⅱ, undergoing elective radical resection of lung cancer under general anesthesia, were enrolled in this study.OPRM1A118G genetic polymorphic sites were analyzed by using polymerase chain reaction technique and ABI 3130 Genetic Analyzer.The patients were divided into wild homozygote group,heterozygote group and mutation homozygote group according to their genotypes.The analgesia pump was connected at the end of operation.Patient-controlled intravenous analgesia solution contained fentanyl 30 μg/kg and ondansetron 8 mg in 200 ml of normal saline.The analgesia pump was programmed to deliver a 2 ml bolus dose with a 15-min lockout interval and background infusion at a rate of 2 ml/h, maintaining the visual analogue scale score ≤3 points.The amount of fentanyl consumed within 24 and 48 h after operation was recorded, and the occurrence of adverse reactions was recorded within 48 h after operation.Results Compared with wild homozygote group, the amount of fentanyl consumed within 24 and 48 h after operation was significantly increased in mutation homozygote group(P0.05).There was no significant difference in the incidence of postoperative adverse reactions between the three groups(P>0.05).Conclusion OPRM1A118G genetic polymorphism is one of the genetic factors contributing to individual variation in fentanyl pharmacodynamics in the patients undergoing radical resection of lung cancer.