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Objective:To evaluate the relationship between hippocampal receptor-interacting protein kinase-1 (RIPK1) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in postoperative neurocognitive dysfunction of aged rats with chronic knee arthritis pain.Methods:Sixty-four healthy male Sprague-Dawley rats, aged 18 months, weighing 500-550 g, were divided into 4 groups ( n=16 each) using a random number table method: chronic knee arthritis pain group (group P), chronic knee arthritis pain+ operation group (group PS), RIPK1 inhibitor necrostatin-1+ chronic knee arthritis pain+ operation group (group NPS), and DMSO+ chronic knee arthritis pain+ operation group (group DPS). The knee arthritis model was prepared by intra-articular injection of monosodium iodoacetate (MIA) 1 mg into the left knee joint, and 12 weeks later exploratory laparotomy was performed under sevoflurane anesthesia. Necrostatin-1 6.25 mg/kg and the equal volume of DMSO were intraperitoneally injected at 1 h before operation in NPS group and DPS group, respectively. Thermal pain threshold was measured at 1 week before MIA injection and 6 and 12 weeks after MIA injection. Morris water maze test was used to evaluate the cognitive function at 7 days after surgery. Hippocampal tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the expression of RIPK1, phosphorylated RIPK1 (p-RIPK1), NLRP3, activated cysteine-aspartic protease caspase-1 (cl-caspase-1), apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot) and contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Thermal pain threshold was significantly decreased at 6 and 12 weeks after MIA injection as compared with that before injection ( P<0.05), and there was no significant difference in thermal pain threshold among the four groups ( P>0.05). Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was up-regulated, and the contents of IL-1β and IL-18 were increased ( P<0.05), and pathological changes of hippocampal neurons were marked in PS group, DPS group and NPS group. Compared with PS group and DPS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, the number of crossing the original platform was increased, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was down-regulated, the contents of IL-1β and IL-18 were decreased ( P<0.05), and pathological changes of hippocampal neurons were significantly attenuated in NPS group. Conclusions:Postoperative hippocampal RIPK1 function is enhanced in aged rats with chronic knee arthritis pain, which then activates NLRP3 inflammasomes, triggering neuroinflammation, and this process may be involved in the mechanism of postoperative neurocognitive dysfunction.
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Objective:To evaluate the role of transient receptor potential melastatin2 (TRPM2) in sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.Methods:Sixty SPF-grade healthy male Sprague-Dawley rats, aged 22 months, weighing 550-600 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group M) and sevoflurane anesthesia+ TRPM2 inhibitor group (group M+ A). M and M+ A groups inhaled 2% sevoflurane for 5 h. In group M+ A, TRPM2 inhibitor ACA 20 mg/kg was intraperitoneally injected at 1 h before sevoflurane inhalation, and the equal volume of dimethyl sulfoxide was intraperitoneally injected in group C and group M. Morris water maze test was performed at 1 day after sevoflurane anesthesia. The escape latency, times of crossing the original platform and time spent in the original platform quadrant were collected. The expression of TRPM2 and necroptosis-related proteins (mixed lineage kinase domain-like protein [MLKL], receptor-interacting protein kinase-1 [RIPK1], phosphorylated MLKL [p-MLKL], and phosphorylated RIPK1 [p-RIPK1]) was detected by Western blot. The cytosolic Ca 2+ concentration in and necroptosis rate of hippocampal neurons were determined by flow cytometry. Results:Compared with group C, the escape latency was significantly prolonged, the times of crossing the original platform were decreased and the time spent in the original platform quadrant was shortened, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was up-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were increased in group M and group M+ A ( P<0.05). Compared with group M, the escape latency was significantly shortened, the times of crossing the original platform were increased, and the time spent in the original platform quadrant was prolonged, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was down-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were decreased in group M+ A ( P<0.05). Conclusions:Hippocampal TRPM2 is involved in the process of sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.
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Objective:To evaluate the effect of necrostatin-1 (Nec-1)pre-treatment on postoperative cognitive function in aged rats with chronic pain due to knee arthritis.Methods:One hundred and twenty healthy male Sprague-Dawley rats, aged 22 months, weighing 550-600 g, were divided into 4 groups ( n=30 each) using a random number table method: chronic pain due to knee arthritis group(group P), chronic pain due to knee arthritis + operation group (group PS), dimethyl sulfoxide (DMSO) + chronic pain due to knee arthritis + operation group (DMSO+ PS group), and necrostatin-1 + chronic pain due to knee arthritis + operation group (Nec-1+ PS group). The inflammation-induced knee arthritis model was developed by injecting monosodium iodoacetate (MIA) into the left joint cavity.The exploratory laparotomy under sevoflurane anesthesia was performed at 12 weeks after intra-articular MIA injection. In Nec-1+ PS group and DMSO+ PS group, necrosstatin-1 6.25 mg/kg and the equal dose of DMSO were intraperitoneally injected at 1 h before surgery, respectively. At 7 days after surgery, the Morris water maze test was used to evaluate the cognitive function, the activation of microglial cells in the dentate gyrus of hippocampus was observed by immunofluorescent staining, and the activation rate of microglia cells was calculated, the necrosis rate of neurons was determined by flow cytometry, the expression of receptor-interacting protein kinase 1 (RIPK1)and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) was determined by Western blot, and the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 were determined by enzyme-linked immunosorbent assay. Results:Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform was reduced, the activation rate of microglia cells in the hippocampal dentate gyrus and necrosis rate of hippocampal neurons were increased, the expression of RIPK1 and p-MLKL was up-regulated, and the contents of pro-inflammatory factors TNF-α, IL-1β and IL-6 in hippocampus were increased in PS, DMSO+ PS and Nec-1+ PS groups ( P<0.05). Compared with PS group and DMSO+ PS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform was increased, the activation rate of microglia cells in the hippocampal dentate gyrus and necrosis rate of hippocampal neurons were decreased, the expression of RIPK1 and p-MLKL was down-regulated, and the contents of pro-inflammatory factors TNF-α, IL-1β and IL-6 in hippocampus were decreased in Nec-1+ PS group ( P<0.05). Conclusions:Necrostatin-1 pre-treatment can improve postoperative cognitive function in aged rats with chronic pain due to knee arthritis, and the mechanism may be related to inhibition of necrosis in hippocampal neurons and reduction of neuroinflammation.
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Objective:To evaluate the effect of pectoral nerve block type Ⅱ combined with esketamine on anxiety and depression in the patients with breast cancer undergoing modified radical mastectomy under general anesthesia.Methods:Eighty-four female patients, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18-25 kg/m 2, undergoing elective first-time modified radical mastectomy for unilateral breast cancer, were divided into 2 groups ( n=42 each) using a random number table method: routine group (R group) and pectoral nerve block type Ⅱ combined with esketamine group (PS group). Sufentanil was used for anesthesia induction and postoperative patient-controlled intravenous analgesia (PCIA) in group R, esketamine was used for anesthesia induction and postoperative PCIA, and type Ⅱ thoracic nerve block was performed under ultrasound guidance after anesthesia induction in group PS, and the rest of the drugs used were the same in both groups.The observer′s assessment of awareness/sedation scale score was recorded at the end of surgery, 30 min after the end of surgery, and at 6, 12 and 24 h after surgery.The Hospital Anxiety and Depression Scale was used to assess patients′ anxiety and depression at 1 day before surgery and at discharge.The intraoperative consumption of anesthetics, emergence time, postanesthesia care unit stay time, pressing times of PCIA, requirement for rescue analgesia, hospital costs, length of postoperative hospital stay, satisfaction scores of surgeons and patients were recorded at discharge.The occurrence of adverse reactions was also recorded after operation. Results:Compared with group R, the observer′s assessment of awareness/sedation scale score were significantly increased at the end of surgery and 30 min after surgery, the consumption of propofol and remifentanil was decreased, the emergence time and postanesthesia care unit stay time were shortened, the incidence of nausea and vomiting was decreased, the Hospital Anxiety and Depression Scale score was decreased at discharge, the incidence of anxiety and depression was decreased, the satisfaction scores of surgeons and patients were increased, and the length of postoperative hospital stay was shortened in group PS ( P<0.05). Conclusions:Pectoral nerve block type Ⅱ combined with esketamine can optimize the efficacy of anesthesia and relieve early postoperative anxiety and depression in the patients undergoing modified radical mastectomy for breast cancer under general anesthesia.
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Objective:To evaluate the improved efficacy of transversus abdominal plane (TAP)-rectus sheath (RS) block combined with general anesthesia in the patients undergoing laparoscopic pancreaticoduodenectomy.Methods:Fifty-six American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes, aged 45-64 yr, with body mass index of 18-25 kg/m 2, scheduled for elective laparoscopic pancreaticoduodenectomy, were divided into 2 groups ( n=28 each) using a random number table method: general anesthesia group (group G) and TAP-RS block plus general anesthesia group (group TRG). In group TRG, after induction of general anesthesia, bilateral TAP-RS block was performed with 0.375% ropivacaine mixed with 0.5 μg/kg dexmedetomidine under ultrasound guidance, 20 ml was injected into the plane of bilateral transverse abdominis, and 10 ml was injected into the posterior sheath of the bilateral rectus abdominis, and the tube was placed on the plane of the transverse abdominis, and 5 ml/h was continuously pumped after operation.In both groups, anesthesia was induced with IV midazolam, sufentanil, etomiddate and cisatracurium besylate and maintained using combined intravenous-inhalational anesthesia, and patient-controlled intravenous analgesia (PCIA) was performed after operation.Pulmonary function indexes were measured before induction of anesthesia (T 0) and at 6, 12 and 24 h after removal of the tracheal tube (T 1-3). Blood gas analysis was performed at T 0, T 2 and T 3.The occurrence of high/low blood pressure, tachycardia/bradycardia, consumption of opioids, PACU stay time, pressing times of PCIA within 24 h after surgery, rescue analgesia, time of passing the first flatus, the first postoperative off-bed time, length of postoperative hospital stay, and 48 h quality of recovery-40 (QoR-40) were recorded.The occurrence of adverse reactions and nerve block-related complications were recorded within 48 h after operation. Results:Conversion to laparotomy during operation was found in 4 patients, changing the scope of resection in 2 patients, and a total of 50 patients were enrolled in this study.Compared with group G, the pressing times of PCIA was significantly reduced, the requirement for postoperative rescue analgesia was decreased, the intraoperative consumption of sufentanil and remifentanil was reduced, the incidence of intraoperative hypertension and tachycardia was decreased, the FEV1, FVC and PEFR were increased at T 2, 3, the 48 h QoR-40 score was increased, the time of passing the first flatus, the first postoperative off-bed time, and length of postoperative hospital stay were shortened, the incidence of nausea, agitation, somnolence, and hypoxemia was decreased ( P<0.05), and no significant change was found in the indicators of blood gas analysis at each time point in group TRG ( P>0.05). Nerve block-related complications were not found in group TRG. Conclusion:Compared with general anesthesia alone, TAP-RS block combined with general anesthesia is helpful in carrying out anesthetic model of low-consumption opioids and improving the quality of early postoperative recovery when used in the patients undergoing laparoscopic pancreaticoduodenectomy.
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Objective To investigate the perioperative risk factors associated with prognoses of patients with acute ischemic stroke accepted mechanical thrombectomy under general anesthesia.Methods The clinical data of 108 patients with acute ischemic stroke,admitted to and accepted mechanical thrombectomy under general anesthesia in our hospital from January l,2016 to October 31,2018,were collected.According to modified Rankin scale (mRS) scores 90 d after surgery,patients were divided into good prognosis group (mRS scores ≤2) and poor prognosis group (mRS scores ≥3).Univariate analysis was used to compare the general data (age,gender,body mass index,and underlying diseases) and perioperative conditions (immediate heart rate,systolic and diastolic blood pressures immediately after admission,operative time,and anesthesia time) between the two groups of patients.Multivariate Logistic regression analysis was used to identify the perioperative risk factors influencing the prognoses of patients with acute ischemic stroke accepted mechanical thrombectomy.Results Among the 108 patients,65 had good prognosis and 43 had poor prognosis.Univariate analysis showed that there was no significant difference in general data between the two groups (P＞0.05),but there were significant differences in heart rate immediately after admission,National Institutes of Health Stroke Scale (NIHSS) scores immediately after admission and 3 d after operation,maximum hemoglobin and blood glucose values from immediately after admission to 3rd d of operation,and thrombolysis in myocardial infarction (TIMI) blood flow classification (P＜0.05).Multivariate Logistic regression analysis showed that heartrate immediately after admission (OR=1.035,95％CI:1.002-1.067,P=0.037) and NIHSS scores 3 d after operation (OR=1.153,95％CI:1.016-1.272,P=0.030) were the perioperative risk factors influencing the prognoses of patients with acute ischemic stroke accepted mechanical thrombectomy.Conclusion For patients with acute ischemic stroke who have rapid heart rate immediately after admission and high NIHSS scores 3 d after mechanical thrombectomy,possibility of poor prognosis should be noticed.
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Objective To evaluate the efficacy of acupuncture combined with tropisetron in treating nausea and vomiting induced by carboprost tromethamine in cesarean section. Methods Sixty-six patients aged 22-40 yr who received carboprost tromethamine and developed nausea and vomiting during cesarean section under lumbar anesthesia, were randomly divided into 3 groups(n=22 each): acupuncture group (group A), tropisetron group(group T)and acupuncture+ tropisetron group(group AT). In group A, 09% normal saline 2 ml was intravenously injected immediately, acupuncture was given at Renzhong, Neiguan and Hegu acupoints with lifting thrusting twirling the acupuncture needle for 10 min. In group T, tropisetron 10 mg was intravenously injected immediately, the needle was placed on Renzhong, Neiguan and Hegu skin surface. In group AT, tropisetron 10 mg was intravenously injected immediately, acupunc-ture was given at Renzhong, Neiguan and Hegu acupoints with lifting thrusting twirling the acupuncture nee-dle for 10 min. The nausea and vomiting score was assessed before anesthesia induction(T0), when nause-a or vomiting occurred(T1)and at 1, 3, 5 and 15 min after acupuncture or administration(T1-5). The degree of patient′s satisfaction with therapeutic effect was recorded. Results Compared with group A, the nausea and vomiting scores were significantly decreased at T4, and the patient's satisfaction score was in-creased in group AT(P<005). Compared with group T, the nausea and vomiting scores were significantly decreased at T2-4and the patient's satisfaction score was increased in group AT(P <005). Conclusion Acupuncture combined with ondansetron can quickly and effectively relieve the nausea and vomiting induced by carboprost tromethamine during cesarean section.
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Objective To synthesize N-(4-fluorophenyl)-N-(4-phenoxyphenyl) cyclopropane-1,1-dicarboxamide (NFNPDB) as small molecular c-Met kinase inhibitor analogue.Methods N-( 4-fluorophenyl )-N-( 4-phenoxyphenyl ) cyclopropane-1, 1-dicarboxamide was synthesized by nucleophilicsubstitution, amidation, etherification, reduction and condensation from diethyl malonate.Results The total yield of target compound was 3.79%, its structure was confirmed by 1 H-NMR.Conclusion The synthesis method of NFNPDB in our research can be easily operated with lost cost and short direction, which lays the foundation for designing the synthetic process of newly small molecular c-Met kinase inhibitor.
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OBJECTIVE@#The aim of this study was to investigate the clinical efficacy of uvulopalatopharyngoplasty (UPPP) with hyoid suspension for patients with obstructive sleep apnea hypopnea syndrome (OSAHS).@*METHOD@#Thirty-eight OSAHS patients underwent UPPP with hyoid suspension. Review the sleep monitoring after 6 months and 1 year and compare the AHI, LSaO 2 and ESS score.@*RESULT@#The average AHI decreased, and blood oxygen saturation increased significantly afer operation.@*CONCLUSION@#UPPP with hyoid suspension is an available and relatively safe surgical approach in OSAHS patients.