Objective To investigate the effects of propofol on gastric mucosal cellular apoptosis after resuscitation of hemorrhagic shock in rabbits.Methods One hundred healthy adult male New Zealand rabbits weighing 2.5-3.0 kg were randomly divided into 5 groups ( n =20 each):group sham operation (group S) ; group hemorrhagic shock ( group M ) and Ⅲ,Ⅳ,Ⅴ 3 propofol groups ( groups P1,2,3 ).Hemorrhagic shock was induced by withdrawing blood from femoral artery.MAP was reduced to 35-40 mm Hg and maintained at this level for 60 min in groups M,P1,P2 and P3.Blood was then transfused back via femoral vein to restore blood volume.In groups P1,2,3 propofol 5 mg/kg was injectel iv at 10 min before ischemia (group P1 ),10 min before (group P2 ) and 20 min of resuscitation (group P3 ) respectively followed by continuous infusion at 20 mg·kg-1 ·h-1 until 90 min of resuscitation.The gastric mucous membrane specimens were obtained at 90 min of resuscitation for macroscopic examination and detection of apoptosis (by TUNEL) and Bcl-2 and Bax protein expression (by immuno-histochemistry).Results Hemorrhagic shock seriously damaged gastric mucous membrane,significantly increased apoptotic index (the number of apoptotic cells/the total number of cells) and Bax protein expression and decreased Bcl-2 protein expression and Bcl-2/Bax ratio in group M as compared with group S.Propofol significantly attenuated hemorragic shock-induced above changes in groups P1 and P2.Concluion Pre- and post-conditioning with propofol can attenuate apoptosis in gastric mucous membrane cells induced by hemorrhagic shock by up-regulating Bcl-2 protein expression and down-regulating Bax protein expression.

Objective:To evaluate the effect of sevoflurane on necroptosis in isolated hippocampal neurons and the relationship with ryanodine receptor.Methods:Primarily cultured hippocampal neurons of fetal rats of Sprague-Dawley rats were inoculated in culture wells (100 μl/well) or culture flasks (3 ml/bottle) at a density of 5×10 5 cells/ml at 7 days of culture and divided into 3 groups ( n=24 each) using a random number table method: control group (group C), sevoflurane group (group S) and ryanodine receptor antagonist group (group R). Group C received routine culture.Ryanodine receptor antagonist Dantrolene at a final concentration of 3 μmol/L was added in group R. Thirty minutes later, the cells were placed in the incubator containing 2% sevoflurane and cultured for 5 h at 37 ℃ in S and R groups.Then cells were collected, the morphology of neurons was observed with an inverted microscope, the concentrations of free calcium ion ([Ca 2+ ] i) in cytoplasm were determined by flow cytometry, the expression of ryanodine receptor and phosphorylated MLKL protein (p-MLKL) was detected by Western blot, the expression of RIP3 was measured by immunofluorescence, and necroptosis rate was calculated. Results:Compared with group C, the [Ca 2+ ] i were significantly increased, the expression of ryanodine receptor and p-MLKL was up-regulated, and the necroptosis rate was increased in S and R groups ( P<0.05). Compared with group S, the expression of ryanodine receptor and p-MLKL was significantly down-regulated, and the [Ca 2+ ] i and necroptosis rate were decreased in group R ( P<0.05). There was no obvious abnormality in the morphology of neurons in group C. The cell body of neurons were shrunk, the processes were broken, and the network between processes was sparse in group S. The cell body was round, and the morphology was close to normal in group R. Conclusion:Sevoflurane can cause necroptosis in isolated hippocampal neurons of rats, and the mechanism is related to up-regulating the expression of ryanodine receptors and leading to calcium overload.

Objective To compare the anterograde amnesia produced by midazolam,propofol and dexmedetomidine when used to supplement sedation during neuraxial anesthesia.Methods Sixty patients of both sexes,aged 18-50 yr,with body mass index of 23-26 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective operation on lower limbs with neuraxial anesthesia,were divided into 3 groups (n =20 each) using a random number table:midazolam group (group M),propofol group (group P) and dexmedetomidine group (group D).When the height of anesthesia was kept below T10,midazolam in a loading dose of O.05 mg/kg was intravenously injected in group M,propofol in a loading dose of O.4 mng/kg was intravenously injected in group P,and dexmedetomidine in a loading dose of 0.6 μg/kg was intravenously injected in group D.The infusion rate of the 3 drugs was adjusted to maintain bispectral index value at 82-86.When Observer's Assessment of Alertness/Sedation Scale scores achieved 3 or 4 after administration,anterograde amnesia was measured by postoperative recall of cards.The development of intraoperative hypotension,bradycardia and respiratory depression was recorded.Results Compared with group M,the incidence of global amnesia was significantly decreased in P and D groups (P＜0.05).There was no significant difference in the incidence of global amnesia between group P and group D (P＞ 0.05).No patients developed hypotension,bradycardia or respiratory depression in three groups.Conclusion Midazolam produces better anterograde amnesia than propofol and dexmedetomidine when used to supplement sedation during neuraxial anesthesia.

Objective To investigate the effect and mechanism of sodium ferulate (SF) on injury of gastric mucosa after traumatic hemorrhage shock resuscitation in rabbits.Methods One hundred healthy rabbits were randomly ( random number) divided into 4 groups ( n =25 in each group):control group ( A),model group ( B),pre-resuscitation SF group (C) and post-resuscitation SF group (D).The gastric mucosa injury model was established by using a method of comminuted fracture of femur and blood depletion.SF 30 mg/kg was injected into vein of rabbits' ear 20 min before resuscitation in group C and 30 min after resuscitation in group D,while rabbits of remaining groups received equal volume of normal saline instead.The gastric mucosa was obtained 90 min after resuscitation.The damage index (DI) of gastric mucosa was observed with method of Guth and the ultra-structure of parietal cell of stomach was observed under electronic microscope and the contents of TXB2 and 6-Keto-PGF1α in gastric tissue homogenate were determined with radio-immunity methods,and the ratios of TXB2/6-Keto-PGF1α were calculated.Data were analyzed by ANOVA ( LSD-t test ),and P ＜ 0.05 was considered as statistical significance. Results Under the electronic microscope,the secreting tubules were observed to be closed tightly in the parietal cells of stomach in the group A,showing a static status.However,in the group B,the number of normal secreting tubules was increased and the lumens were enlarged obviously.Compared with the group B,the number of normal secreting tubules was decreased and the enlargement of secreting tubules was not obvious in group C.The degree of changes in secreting tubules in group D was that between group C and group B.Compared with group A,the DI,the content of TXB2 and ratio of TXB2 to 6-Keto-PGF1α in other three groups were higher [DI: (81.5+13.6), (61.3+18.2), (70.5+17.2) vs.(4.2+2.7); the contents of TXB2:(4.95 +0.51),(3.75+0.64),(4.39±0.69) vs.(2.76±0.44); and the ratios of TXB2 to 6-KetoPGF1α:(0.064±0.002),(0.037±0.005), (0.049±0.002) vs.(0.027±0.002)] (P＜0.01),but the contents of 6-Keto-PGF1α in other 3 groups were lower [ (77.9±8.9),(96.4±11.2),(89.2+11.4) vs. (109.3±7.6)] (P＜0.05orP＜0.01).Compared with group B,theDI [ (61.3±18.2),(70.5±17.2) vs.(81.5±13.6)] and the contents of TXB2 [ (3.75±0.64), (4.39±0.69) vs.(4.95±0.51)] and the ratios ofTXB2 to6-Keto-PGF1α [ (0.037±0.005), (0.049±0.002) vs.(0.064 ±0.002)] in groups C and D were lower (P ＜ 0.05 or P ＜ 0.01 ),but the contents of 6-KetoPGF1α in groups C and D [ (96.4 ± 11.2),( 89.2 ± 11.4) vs.(77.9 ± 8.9) ] were higher ( P ＜ 0.05 or P ＜ 0.01 ).Compared with group C,the DI [ ( 70.5 ± 17.2) vs.61.3 ± 18.2) ] and the contents of TXB2 [ (4.39 ± 0.69) vs.(3.75 ± 0.64) ] and the ratios of TXB2 to 6-Keto-PGF1α [ (0.049 ± 0.002 ) vs.(0.037 +0.005) ] in group D were higher ( P ＜ 0.05 or P ＜ 0.01 ),but the content of 6-Keto-PGF1α in group D [ ( 89.2 ± 11.4 ) vs.(96.4 ± 11.2) ] was lower ( P ＜ 0.05 ).Conclusions SF can attenuate the injury of gastric mucosa after traumatic hemorrhage shock resuscitation in rabbits,and its therapeutic effects is better when it is administered before resuscitation than those as it is administered after resuscitation.The possible mechanism is associated with the effects of improving balance between TXB2 and 6-Keto-PGF1α and inhibiting the secreting function of parietal cell of stomach.

Objective To evaluate the effect of nimodipine on the activity of calcineurin (CaN) in the hippocampus of aged rats.Methods Sixty healthy male Sprague-Dawley rats,aged 18 months,weighing 550-650 g,were divided into 2 groups (n=30 each) using a random number table:surgery group (group S) and nimodipine group (group N).Nimodipine 1 mg/kg was intraperitoneally injected in group N,while the cqual volume of normal saline was given instead in group S,and 30 min later exploratory laparotomy was performed.Ten rats in each group were randomly selected on 1 day before operation and 3 and 7 days after operation,and Morris water maze test was performed.After the end of Morris water maze test,10 rats were selected and sacrificed,brains were removed,and hippocampi were isolated for detection of apoptosis in hippocampal neurons (by flow cytometry) and expression of CaN,phosphor-BAD (p-BAD) and caspase-3 in hippocampal tissues (by Western blot).Apoptotic rate was calculated.Results Compared with the value at 1 day before operation,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the time of staying at the platform quadrant was shortcned,apoptotic rate was increased,and the expression of CaN,p-BAD and caspase-3 in hippocampal tissues was up-regulated at each time point after operation in group S (P＜0.05).Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the time of staying at the platform quadrant was prolonged,apoptotic rate was decreased,and the expression of CaN,p-BAD and caspase-3 in hippocampal tissues was down-regulated at each time point after operation in group N (P＜0.05).Conclusion The mechanism by which nimodipine inhibits apoptosis in hippocampal neurons and reduces postoperative cognitive dysfunction may be related to inhibition of CaN activation in aged rats.

Objective To evaluate the effect of nimodipine combined with 7.5％ hypertonic saline (HS) on postoperative cognitive function in aged rats.Methods Ninety-six healthy male Wistar rats,aged 18 months,weighing 450-500 g,were assigned into 4 groups (n=24 each) using a random number table:splenectomy group (group S),nimodipine group (group N),group HS and nimodipine plus HS group (group N+HS).Nimodipine 1 mg/kg was intraperitoneally injected in group N.In group HS,7.5％ HS 4 ml/kg was injected via the caudal vein.The equal volume of normal saline was injected intraperitoneally or via the caudal vein in group S.Splenectomy was performed under sevoflurane anesthesia at 30 min after the end of administration.On 1 day before operation and 3 and 7 days after operation,Morris water maze test was performed,and blood sainples from the caudal vein were simultaneously collected for determination of the concentrations of serum S100β protein and neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay.Results Compared with group S,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in N,HS and N+HS groups (P＜0.05).Compared with group N or group HS,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in group N+HS (P＜0.05).Conclusion Nimodipine combined with 7.5％ HS exerts better efficacy than either alone in improving postoperative cognitive function in aged rats.

Objective:To explore the effect of team psychological counseling in patients with inflammatory bowel disease (IBD) .Methods:From January to December 2020, 90 IBD patients admitted to the Department of Gastroenterology of the Fifth Affiliated Hospital of Zhengzhou University were selected as the research object by convenience sampling. According to the random number table method, the patients were divided into the observation group and the control group, 45 cases in each group. The control group carried out routine nursing, and the observation group conducted team psychological counseling on this basis. The Morisky Medication Adherence Scale (MMAS) , Inflammatory Bowel Disease Self-efficacy Scale (IBD-SES) and the Hospital Anxiety and Depression Scale (HADS) were used to evaluate the intervention effect.Results:After the intervention, the scores of MMAS and IBD-SES in the observation group were higher than those of the control group, and the anxiety scores and depression scores of HADS were lower than those of the control group, and the differences were all statistically signifcant ( P<0.05) . Conclusions:Team psychological counseling can increase the medication compliance and self efficacy of IBD patients, alleviate the patients' poor psychological state.

Objective:To analyze the clinical phenotype and genotype characteristics of infantile spasm (IS) associated with UBA5 gene mutation. Methods:Four cases of IS caused by UBA5 gene variation diagnosed at the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were retrospectively analyzed.The clinical manifestations, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), treatment, and follow-up results were summarized. Results:In this study, 4 cases (3 males and 1 female) were clinically diagnosed with IS and carried complex heterozygous variation of UBA5 gene.Genetic analysis confirmed that a total of 6 different mutation sites were found, five of which were unreported.All the 4 cases presented with epileptic spasms at the age of 1 d to 8 months after birth, and 2 cases had focal seizures during the course of disease.The EEG of 4 cases showed hypsarrhythmia and cluster or isolated epileptic spasms were detected.Of the 3 patients who had brain MRI results, 2 cases showed nonspecific abnormalities and 1 case was normal.All the 4 patients had developmental delayed before seizure onset, and regressed to varying degrees and made slow progress after onset.One case had microcephaly, and 3 cases had hypertonia.At the last follow-up, the age of the 4 patients ranged from 7 months to 6 years and 4 months.All 4 patients were treated with multiple antiepileptic drugs, but none of them were under control. Conclusions:Children with IS associated with UBA5 gene variation have an early onset age, often accompanied by developmental delayed, microcephaly, dystonia, and refractory seizures.

Objective:To evaluate the role of interleukin 1β (IL-1β)/c-Jun N-terminal kinase (JNK) pathway in sevoflurane-induced necroptosis of rat hippocampal neurons in vitro. Methods:Primarily cultured hippocampal neurons of Sprague-Dawley rat fetuses were inoculated into 96-well plates (cell density: 1×10 4 cells/ml, 200 μl/hole) and 6-well plates (cell density: 1×10 6 cells/ml, 2 ml/hole). The cells were divided into 3 groups ( n=20 each) using a random number table method after being cultured for 7 days: control group (group C), sevoflurane group (group S) and IL-1 receptor antagonist group (group I). Group C received routine culture, IL-1 receptor antagonist IL-1ra 1 μg/μl was added, and the cells were incubated for 30 min in group I, and in addition the cells were placed in the incubator containing 2% sevoflurane and cultured for 5 h at 37 ℃ in S and I groups.The cells were collected for microscopic examination of the morphology of neurons (with an inverted microscope) and for determination of the cell necroptosis rate (by flow cytometry), cell viability (by MTT method), and expression of IL-1β, interleukin-1 receptor type I (IL-1RI), interleukin-1 receptor accessory protein (IL-1RAcP), phosphorylated JNK (p-JNK) ), receptor-interacting protein 1 (RIP1), RIP3 and phosphorylated mixed lineage kinase-like (p-MLKL) (by Western blot ). Results:Compared with group C, the cell viability was significantly decreased, the necroptosis rate was increased, and the expression of IL-1β, IL-1RI, IL-1RAcP, p-JNK, RIP1, RIP3 and p-MLKL was up-regulated in group S ( P<0.05). Compared with group S, the cell viability was significantly increased, the necroptosis rate was decreased, and the expression of IL-1β, IL-1RI, IL-1RAcP, p-JNK, RIP1, RIP3 and p-MLKL was down-regulated in group I ( P<0.05). There was no obvious abnormality in the morphology of neurons in group C. The cell body of neurons was shrunk, the processes were broken, and the network between processes was sparse in group S. The cell body was round, and the morphology was close to normal in group I. Conclusion:The mechanism by which sevoflurane induces necroptosis of rat hippocampal neurons in vitro is related to activation of IL-1β/JNK pathway.

Objective:To evaluate the role of RhoA/ROCK2 signaling pathway in multiple exposures to sevoflurane-induced long-term cognitive impairment in neonatal rats.Methods:Sixty SPF healthy neonatal Sprague-Dawley rats of either sex, aged 6 days, weighing 12-20 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), multiple exposures to sevoflurane group (group S) and RhoA/ROCK2 signaling pathway inhibitor Y-27632 group (group Y). Group S and group Y inhaled 3% sevoflurane for 2 h at days 6, 7 and 8 after birth.In group Y, Y-27632 5 mg/kg was intraperitoneally injected before sevoflurane anesthesia.The spontaneous activity was evaluated by open field test on day 35 after birth.The cognitive function was detected by Morris water maze test at day 36 after birth.The rats were sacrificed after Morris water maze test, and the hippocampal tissues were isolated for determination of the apoptosis rate of hippocampal neurons and cytoplasmic calcium concentration ([Ca 2+ ] i) (by flow cytometry) and expression of phosphorylated RhoA (p-RhoA), ROCK2 and cleaved-caspase-3 (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no significant difference in movement speed, distance and time of stay in the open field center in the open field test among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal neurons and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological injury to hippocampal neurons was found in group S. Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, the apoptosis rate of hippocampal neurons and [Ca 2+ ] i were decreased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was down-regulated ( P<0.05), and the pathological injury to hippocampal neurons was attenuated in group Y. Conclusions:The mechanism by which multiple exposures to sevoflurane induces long-term cognitive impairment is related to activation of RhoA/Rock2 signaling pathway and induction of apoptosis rate of hippocampal neurons in neonatal rats.