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In recent years, monotherapy and combination therapy with immune checkpoint inhibitors (ICIs) have achieved good efficacy in a variety of malignancies from solid tumors to lymphomas and have become a standardized and systematic treatment modality for many cancers. However, there is still a lack of studies on the safety of ICIs in hepatitis B virus (HBV)-infected patients with malignancies, and early studies have reported HBV reactivation due to ICI antitumor therapy in clinical practice. With reference to related literature, this article reviews the recent clinical trials and application of ICIs in cancer patients with chronic viral infection and clarifies the efficacy and safety of ICIs in this special population, in order to provide a reference for clinical medication.
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Objective To evaluate the safety and efficacy of irreversible electroporation (IRE) combined with neoadjuvant chemotherapy in patients with locally advanced pancreatic cancer. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, China Biomedical Literature Database, CNKI, Wanfang, and VIP databases for articles dated from the establishment of each database to March 2022. Meta-analysis was performed using RevMan5.4 software. Results A total of 3970 patients with locally advanced pancreatic cancer were enrolled in eight studies, including one randomized controlled trial, four retrospective studies, and three prospective studies. The patients were divided into the combined therapy group with 344 patients and the chemotherapy-only group with 3626 patients. Meta-analysis showed that the overall survival of patients in the combined therapy group was significantly higher than that in the chemotherapy-only group (OR=4.52; 95%CI: 2.63-7.77; P < 0.00001). However, no significant difference existed in the disease control rate between the combined therapy group and the chemotherapy-only group (OR=0.58; 95%CI: 0.02-18.74; P=0.76). Moreover, no significant difference existed in the disease progression between the two groups (OR=0.49; 95%CI: 0.23-1.02; P=0.06). The combination of neoadjuvant chemotherapy and IRE had no significant effect on the incidence of adverse reactions of gastrointestinal reaction (OR=0.37; 95%CI: 0.10-1.34; P=0.13) and bone marrow suppression (OR=0.61; 95%CI: 0.26-1.40; P=0.24). Conclusion IRE combined with neoadjuvant chemotherapy can remarkably improve the prognosis of patients with locally advanced pancreatic cancer, and significantly prolong the overall survival.
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Objective:To investigate the expression of Macrophage migration-inhibitory factors (MIF) in hepatocellular carcinoma (HCC) tissues and its interaction with ERK1/2 signaling pathway, so as to establish a theoretical basis for further studying the molecular mechanism of MIF promoting HCC.Methods:From February 2020 to August 2021, 52 cases of hepatocellular carcinoma (HCC) tissues based on hepatitis B cirrhosis (HBV-LC) and 52 cases of adjacent tissues in Tianjin Medical University Cancer Hospital and 940th Hospital of Joint Logistic Support Force of PLA were collected as the experimental group, including 39 males and 13 females, aged 35-65 years. And 20 cases of normal liver tissue were selected as the control group. Immunohistochemistry was used to detect the expression of MIF, ERK1/2 and p-ERK1/2 proteins in liver tissues of the two groups, and in situ hybridization was used to detect the expression of ERK1/2 nucleic acid in liver tissues of the two groups.HepG2 HCC cells and L-02 normal hepatocytes were co-cultured with different concentrations of rMIF, the expression and phosphorylation levels of ERK1/2 and JNK1 proteins in the two kinds of liver cells were detected by Western-blot, and the expression levels of ERK1/2 nucleic acids in the two kinds of liver cells were detected by RT-PCR. One-way ANOVA was used for measurement data and χ 2 test was used for counting data. Results:The expressions of MIF, ERK1/2, p-ERK1/2 and ERK1/2 mRNA were significantly increased in HCC and para-cancer tissues (the expression of MIF in HCC group was 78.8%, and that in adjacent group was 75.0%; ERK1/2 80.8% in HCC group and ERK1/2 71.8% in paracancerous group. The expression of p-ERK1/2 75.0 % in HCC group and 46.2% in paracancerous group were respectively detected. ERK1/2 mRNA was expressed in HCC group 76.9%, ERK1/2 mRNA expression in paracancerous group 78.8%), and the differences were statistically significant compared with normal liver tissues ( P<0.05), but there was no significant difference between HCC and para-cancer tissues ( P>0.05). The expressions of ERK1/2, p-ERK1/2 and ERK1/2 mRNA in HepG2 HCC cells were significantly increased with the increase of rMIF concentration, and the increase was most obvious when rMIF concentration was 200 ng/ml, and the difference was statistically significant compared with L-02 normal hepatocytes ( P<0.05). Conclusion:MIF, ERK1/2 and p-ERK1/2 are highly expressed in HCC tissues and HepG2 HCC cells, suggesting that MIF promotes the occurrence and development of hepatocellular carcinoma through ERK1/2 signaling pathway.
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Objective:To compare the effect of rapid frozen section and paraffin section in the diagnosis of ovarian tumor.Methods:From February 2017 to December 2018, 80 tissue samples of ovarian tumor were selected from the First People's Hospital of Yongkang, all of them were diagnosed by rapid frozen section and paraffin section.The examination time and diagnosis results of the two methods were compared.Results:The time of rapid frozen section examination was (34.48±4.16)min, which was shorter than that of paraffin section pathology diagnosis [(182.63±2.12)min], the difference was statistically significant( t=283.804, P<0.05). The pathological diagnosis of benign tumor, malignant tumor and borderline tumor of paraffin section were 45 cases, 21 cases and 14 cases, respectively, which of rapid frozen section examination were 44 cases, 19 cases and 13 cases, respectively.The perfect match rate, delayed diagnosis rate and misdiagnosis rate were 95.00%(76/80), 1.25%(1/80) and 3.75%(3/80), respectively. Conclusion:Compared with the pathological diagnosis of paraffin section, the rapid frozen section examination of ovarian tumor has shorter time and higher rate of complete coincidence, but has misdiagnosis.Doctors should improve the operation skills and the quality of section materials and production.
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Objective:To investigate the clinical features and immunohistochemical analysis of 120 transrectal ultrasound-guided prostate biopsies, thus to improve the clinical and pathological diagnosis accuracy of prostate cancer.Methods:From July 2018 to July 2019, the clinical data of 120 patients with prostate disease underwent transrectal ultrasound guided prostate biopsy in the First People's Hospital of Yongkang were selected.The clinicopathological features and immunohistochemical analysis were performed in the biopsy samples.Results:Of the 120 patients, 45 patients with prostate cancer(PCA) were diagnosed by pathology, accounting for 37.5%; 3 patients with prostatic epithelial neoplasia(PIN) grade I, accounting for 2.5%; 55 patients with benign prostatic hyperplasia, accounting for 45.8%; 5 cases of atypical adenomatoid hyperplasia, accounting for 4.2%; 12 cases of chronic prostatitis, accounting for 10.0%.Pathological results showed that the glandular structure of the prostate cancer was disordered, complicated and diverse, interstitial infiltration, and partial invasion of the pathological changes of the nerve.According to the Gleason scoring method, among 45 patients with prostate cancer, 6 patients were highly differentiated adenocarcinoma(<5 points), 25 patients were moderately differentiated (6-7 points), and 14 patients were poorly differentiated (≥8 points). Immunohistochemical analysis showed that p63 and CK34βE12 expression was negative in prostate cancer patients, and P504S and PSA expression was positive.Conclusion:Transrectal ultrasound guided prostate puncture has great significance for the diagnosis of prostate cancer.It is safe, accurate and easy to operate.It is an effective diagnostic method.Comprehensive judgment of clinical pathological features and immunohistochemical analysis can help differential diagnosis of prostate diseases and improve the accuracy of diagnosis.
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Objective:To compare the efficacy of HES 130/0.4 and acetate Ringer′s solution (A-HES) and HES 130/0.4 and normal saline (NS-HES) for volume therapy in the patients undergoing non-cardiac surgery with general anesthesia.Methods:Two hundred and fifty American Society of Anesthesiologist physical status Ⅰ or Ⅱ patients of both sexes, aged 18-64 yr, with body mass index of 18-32 kg/m 2, undergoing noncardiac surgery with general anesthesia, were divided into group A-HES and group NS-HES using the stratified block randomization technique.A-HES and NS-HES 15 ml/kg were intravenously infused over 1 h immediately after induction of anesthesia in A-HES and NS-HES groups, respectively.Mean arterial pressure (MAP), heart rate (HR) and central venous pressure (CVP) were recorded before and after infusion, and the maximum changing rate of MAP and HR and the maximum change in CVP were calculated.The pH value, BE and HCO 3- were recorded before infusion and at 15 min after the end of infusion, and Hb, Hct, electrolytes, blood glucose, blood biochemical parameters and parameters of coagulation function were measured.The occurrence of abnormal blood biochemical parameters, blood glucose, and parameters of coagulation function, intraoperative requirement for vasoactive drugs, occurrence of HES-related adverse events, and intraoperative fluid intake and output were recorded. Results:A total of 251 cases were actually enrolled in this study, with 125 cases in group A-HES, and 126 cases in group NS-HES.Compared with group NS-HES, no significant change was found in the maximum changing rate of MAP and HR and the maximum change in CVP ( P>0.05) in group A-HES, and non-inferiority analysis showed that group A-HES was not inferior to group NS-HES.Compared with group NS-HES, the concentrations of BE and HCO 3-, K + , Ca 2+ and Mg 2+ were significantly increased, the concentrations of Na + and Cl - were decreased, the PT was shortened, the incidence of abnormal PT was decreased at 15 min after the end of infusion ( P< 0.05), and no significant change was found in the other parameters mentioned above in group A-HES ( P>0.05). Conclusion:The volume expanding effect of A-HES and its effect on liver and kidney function are not significantly different from those of NS-HES, however, A-HES has certain advantages in maintaining acid-base balance, electrolyte stability and coagulation function.
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Objective To evaluate the effects of dexmedetomidine with different-dose on the hemodynamics during anesthesia induction in patients undergoing off-pump coronary artery bypass grafting. Methods Sixty patients undergoing off-pump coronary artery bypass grafting were selected, with ASA grade Ⅱ - Ⅲ, NYHA cardiac functional grading Ⅱ - Ⅲ, and left ventricles ejection fraction >45%. The patients were divided into D1 group, D2 group and control group by table of random digit method with 20 cases each. In D1 group, intravenous infusion dexmedetomidine 0.3μg/kg was given for 20 min before anesthesia induction;in D2 group, intravenous infusion dexmedetomidine 0.6μg/kg was given for 20 min before anesthesia induction;in control group, intravenous infusion the same volume of 0.9% sodium chloride was given before anesthesia induction. The mean arterial pressure (MAP), heart rate, cardiac output and stroke volume variation (SVV) were recorded before infusion dexmedetomidine (T0), before anesthesia induction (T1), 3 min after anesthesia induction (T2), trachea cannula (T3) and 5 min after trachea cannula (T4). The adverse cardiovascular events and drug intervention were recorded during anesthesia induction. Results There were no statistical differences in MAP, heart rate, cardiac output and SVV at T0 among 3 groups (P>0.05). Compared with that in control group, the heart rate at T1, T2, T3 and T4 in D1 group were decreased, the MAP, heart rate, cardiac output and SVV at T1, T2, T3 and T4 in D2 group were decreased, and there were statistical differences (P<0.05). Compared with that at T0, the heart rate at T1, T2, T3 and T4 in D1 group were decreased, the MAP, heart rate, cardiac output and SVV at T3 in control group were increased, the MAP, heart rate, cardiac output and SVV at T1, T2, T3, T4 in D2 group were decreased, and there were statistical differences (P<0.05). Compared with that in D1 group, the MAP, heart rate, cardiac output and SVV at T2, T3 and T4 in D2 group were decreased, and there were statistical differences (P<0.05). The rates of adverse cardiovascular events in D1 group and D2 group were significantly lower than those in control group:35%(7/20) and 40%(8/20) vs. 95%(19/20), the rate of drug intervention in D1 group was significantly lower than that in control group and D2 group:10% (2/20) vs. 45% (9/20) and 35% (7/20), and there were statistical differences (P<0.05). Conclusions Dexmedetomidine (0.3 μg/kg) is beneficial for the stability of hemodynamics before anesthesia induction in patient undergoing off-pump coronary artery bypass grafting.
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Objective To evaluate the effect of isoflurane or sevoflurane inhalation before and after gestation on the offspring brain development. Methods Thirty female adult Sprague Dawley rats were randomly assigned into 5 groups(n=6 each):control group(group C),group that ex?posed to isoflurane with the concentration of 1.6%for 6 hours before gestation(group BI),group that exposed to isoflurane with the concentration of 1.6%at the 6th,10th,14th and 18th day for 6 hours(group PI),group that exposed to sevoflurane with the concentration of 2.4%for 6 hours before gestation(group BS),and group exposed to sevoflurane with the concentration of 2.4%at the 6th,10th,14th and 18th day for 6 hours after gestation (group PS). Twelve offspring rats from pregnant rats in each group were chosen on the day of birth(T1),and 7th,14th and 28th days after birth(T2, T3 and T4)and sacrificed,and the hippocampi were then isolated. Hematoxylin and eosin stain were adopted to observe the tissue pathological change. Electron microscope was used to observe the neuron ultrastructure change of hippocampus. Immolunohistochemistry was used to detect cas?pase?3,the expression of growth associated protein?43(GAP?43)and neuronal nitric oxide synthase(nNOS). Results Compared with group C, no significant change was found in caspase?3,GAP?43 and nNOS expression in offspring rat hippocampus in groups BI and BS(P>0.05),and no damage change in hippocampal was seen by HE staining and electron microscopy. In group PI and PB,the expression of caspase?3 was significantly up?regulated,the expression of GAP?43 and nNOS was down?regulated at T1 to T3(P<0.01),and structural changes in cell were seen by electron microscopy. In group PI,significant pathological changes in hippocampal were seen by HE staining at T1 to T3. Compared with group PI,the expres?sion of GAP?43 and nNOS was significantly up?regulated(P<0.01),and the expression of caspase?3 was down?regulated at T1 to T3(P<0.01). Conclusion Isoflurane or sevoflurane inhalation before gestation does not affect the offspring brain development,while isoflurane or sevoflurane in?halation after gestation can induce transient abnormal change of offspring brain development,and isoflurane′s toxicity was greater than sevoflurane.
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Objective To evaluate the effects of curcumin on matrix metalloproteinase-9 (MMP-9)/tissure inhibitor of metalloproteinase-1 (TIMP-1) balance during limb ischemia-reperfusion (I/R)-induced lung injury in rats.Methods Twenty-four adult male Sprague-Dawley rats,aged 6-8 months,weighing 250-300 g,were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (group S) ; group I/R; curcumin + I/R group (group C + I/R).Limb ischemia was induced by occlusion of bilateral femoral arteries for 2 h followed by reperfusion for 3 h in I/R and C + I/R groups.At 2 h before ischemia,curcumin 200 mg/kg was injected intraperitoneally in group C + I/R,while the equal volume of normal saline was given instead in the other groups.Arterial blood samples were taken at 3 h of reperfusion for blood gas analysis and PaO2 was recorded.The animals were then sacrificed and the lungs were removed immediately for determination of wet/dry lung weight (W/D) ratio,myeloperoxidase (MPO) activity and MMP-9 and TIMP-1 contents.The ratio of MMP-9/ TIMP-1 was calculated.Results Compared with group S,PaO2 was significantly decreased,and W/D ratio,MPO activity,MMP-9 content and the ratio of MMP-9/TIMP-1 were significantly increased (P ＜ 0.05),while no significant change was found in TIMP-1 content in group I/R (P ＞ 0.05).Compared with group I/R,PaO2 and TIMP-1 content were significantly increased,and W/D ratio,MPO activity,MMP-9 content and the ratio of MMP-9/TIMP-1 were significantly decreased in group C + I/R (P ＜ 0.05).Conclusion The mechanism by which curcumin attenuates lung injury induced by limb I/R is related to decreased MMP-9 content,elevated TIMP-1 content and regulated balance between MMP-9 and TIMP-1 in the lung tissues of rats.
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Objective To evaluate the effect of isoflurane or sevoflurane inhalation before and after gestation on the N-methyl-D-aspartate (NMDA) receptor expression in offspring rat hippocampus.Methods Thirty female adult Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were randomly assigned into 5 groups (n =6 each):control group (group C),exposure to isoflurane before gestation group (group BI),exposure to isoflurane during gestation period group (group PI),exposure to sevoflurane before gestation group (group BS),exposure to sevoflurane during gestation period group (group PS).The rats inhaled 1.6％ isoflurane for 6 h at 1 day before gestation in group BI.The rats inhaled 1.6％ isoflurane for 6 h at 6,10,14 and 18 day gestation in group PI.The rats were exposed to 2.4％ sevoflurane for 6 h before gestation in group BS.The rats were exposed to 2.4％ sevoflurane for 6 h at 6,10,14 and 18 day gestation in group PS.Twelve offspring rats from pregnant rats in each group were chosen on the day of birth (T1),and 7th,14th and 28th days after birth (T2-4) and sacrificed,and the hippocampi were then isolated for determination of the expression NMDA receptor (NR1,NR2A and NR2B).Results Compared with group C,no significant change was found in NMDA receptor expression in off spring rat hippocampus in groups BI and BS (P ＞ 0.05),and the expression of NR1 and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1-3 (P ＜0.05),and no significant change was found in NMDA receptor expression at T4 in groups PI and PS (P ＞ 0.05).Compared with group PI,the expression of NRI and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1 3 (P ＜ 0.05 or 0.01),and no significant change was found in N MDA receptor expression at T4 in group PS (P ＞ 0.05).Conclusion Isoflurane or sevoflurane inhalation before gestation does not affect the NMDA receptor expression in offspring rat hippocampus,while isoflurane or sevoflurane inhalation after gestation can induce abnormal expression of the NMDA receptor in offspring rat hippocampus,which may result in apoptosis in hippocampal cells and abnormality in the development of nervous system and cognitive function.
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Objective To investigate the effect of sufentanil postconditioning on cardiomyocyte apoptosis during myocardial ischemia-reperfusion (I/R) in rats.Methods Thirty-six male Sprague-Dawley rats weighing 250-280 g were randomly divided into 3 groups ( n =12 each):sham operation group (group S),I/R group and sufentanil postconditioning group (group SP).Myocardial I/R was induced by occlusion of the left coronary artery for 30 min followed by 120 min reperfusion.Sufentanil 3.0μg/kg was injected iv at the beginning of reperfusion in group SP.HR and MAP were recorded during I/R.The rats were sacrificed at 120 min of reperfusion and their hearts were removed for determination of infarct size,number of apoptotic cardiomyocytes,and the expression of Bax mRNA and Bcl-2 mRNA,and apoptotic index was caculated.Results There was no significant difference in HR among the 3 groups ( P ＞ 0.05 ).Compared with group S,MAP and Bcl-2 mRNA expression were significantly decreased,apoptotic index and Bax mRNA expression increased in group I/R,and apoptotic index,and the expression of Bax mRNA and Bcl-2 mRNA were increased in group SP (P ＜ 0.05).Compared with group I/R,the infarct size,apoptotic index and Bax mRNA expression were decreased,and Bcl-2 mRNA expression was increased in group SP (P ＜ 0.05).Conclusion Sufentanil postconditioning can attenuate myocardial I/R injury in rats by up-regulating Bcl-2 expression,down-regulating Bax expression and inhibitting cardiomyocyte apoptosis.
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Objective To investigate the efficiency of transduction of recombinant adenovirus-mediated human endothelial nitric oxide synthase (eNOS) into lung tissue by repeated intratracheal transfection in rats.Methods Sixty 3-4 month old male Wistar rats weighing 220-280 g were randomly divided into 2 groups:control group (group C,n =10) and eNOS gene transduction group (group T,n =50).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 35 mg/kg,tracheally intubated and mechanically ventilated (VT 2.5 ml,RR 60 bpm,FiO2 1.0).Recombinant adenovirus carrying human eNOS gene was given as gift by Professor Gerard from Texas University,Southwest Medical Center.In group T 50 μl of the recombinant adenovirus in concentration of 5 × 109 PFU/ml was instilled into trachea every 5 minutes for 12 times,while in group C equal volume of vector conservation solution was instilled instead.Pulmonary arterial blood samples were obtained at 2,5,7,14 and 21 d after intratracheal transfection (n =10 at each time point) for determination of serum NO concentration.The animals were immediately sacrificed after blood sample collection for determination of expression of eNOS protein in the lung tissue and RNA.The eNOS expression in the trachea,bronchus,lung,liver,spleen and kidney was detected by immuno-histochemistry.Results The serum NO concentrations were significantly higher at all time points in group T than in group C.The eNOS expression was detected in the epithelial cells of trachea and bronchi,and endothelial cells of alveoli and pulmonary blood vessels in group T but not in group C.eNOS expression was not detected in liver,spleen and kidney at 7 d after intratracheal transfection in group T.Conclusion Human eNOS gene mediated by recombinant adenovirus was transducted into rat lung tissue with normal enzyme activity by repeated intratracheal administration without being detected in distant organs.
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Objective To investigate the effects of simvastatin preconditioning on the pulmonary heme oxygenase-1 (HO-1) expression in rats with lung injury induced by ischemia-reperfusion (I/R) of hind limbs. Methods Forty-eight adult male SD rats weighing 250-300 g were randomly divided into 6 groups ( n = 8 each) : sham operation group (group S) ; I/R group; I/R + simvastatin 1,5, 10 mg/kg groups (S1 , S2, S3 groups) ; simvastatin control group (group SC) . I/R of hind limbs was produced by occlusion of bilateral femoral arteries for 2 h followed by 3 h reperfusion. Croups S1 , S2 , S3 received simvastatin 1, 5, 10 mg/kg respectively via an oro-gastric tube for 3 days before I/R. Group SC received simvastatin 10 mg/kg via an oro-gastric tube for 3 days. Arterial blood samples were taken at 3 h of reperfusion for blood gas analysis and PaO2 and PaCO2 were recorded. The animals were then sacrificed and the lungs removed immediately for pathologic examination and determination of the wet/dry lung weight ratio (W/D ratio), superoxide dismutase (SOD) activity and polymorphonuclear neutrophil (PMN) count . Hie expression of HO-1 mRNA and protein in lung tissues was detected using RT-PCR and Western blot analysis respectively.Results Alveolar edema, localized pulmonary atelectasis and large amount of PMN infiltration were found in I/R group and were ameliorated in S1, S2, S3 groups. Compared with group S, PaO2 and PaCO2 were significantly decreased in I/R group, W/D ratio and PMN count were increased and SOD activity was significantly decreased in I/R, S1 , S2 groups, and expression of HO-1 mRNA and protein was up-regulated in the other five groups ( P ＜ 0.05). PaO2, PaCO2 and SOD activity were significantly increased, W/D ratio and PMN count were significantly decreased, and HO-1 mRNA and protein expression was up-regulated in S1, S2 and S3 groups as compared with I/R group ( P ＜ 0.05 or 0.01). W/D ratio and PMN count were gradually decreased, SOD activity was gradually increased, and HO-1 mRNA and protein expression was gradually up-regulated in S1, S2 and S3 groups. Conclusion Simvastatin preconditioning has protective effect against lung injury induced by I/R of hind limbs in rats through up-regulation of HO-1 expression in the lung tissues and in a dose-dependent manner.
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ObjectiveTo investigate the effect of controlled low perfusion pressure on expression of phosphor-Akt (p-Akt) and phosphor-ERK1/2 (p-ERK1/2) following spinal ischemia-reperfusion (1/R) in rabbits.MethodsThirty-six Japanese long-ear white rabbits aged 3 months weighing 2.0-2.5 kg were randomly divided into 3 groups ( n ＝ 12 each):group sham operation (group S) ; group spinal I/R (group I/R) and group controlled low perfusion pressure (group LP).Auricular artery and femoral artery were carnulated for proximal and distal BP monitoring.A 4F catheter with a balloon at the tip was inserted into abdominal aorta.The tip was positioned 1 cm below left renal artery.Spinal ischemia was induced by inflating the balloon until the distal MAP < 20 mm Hg,and maintained for 25 min.During the first 10 min of reperfusion the distal MAP was increased to 45-55 mm Hg by partially deflating the balloon.Then the balloon was fully deflated to allow complete reperfusion.The function of lower limbs was assessed with Tarlov score (0 ＝ no detectable movement,4 ＝ normal function) at 1,3,7,28 d of reperfusion.Au the animals were sacrificed at 1 d of reperfusion in each group.The lumbar segment L3-5 of the spinal cord was removed for microscopic examination and determination of expression of p-Akt and p-ERK1/2 by immuno-histochemistry) and detection of neuronal apoptosis in dorsal horn (by TUNEL).ResultsSpinal I/R significantly decreased Tarlov scores,and increased the number of apoptotic cells and expression of p-Akt and pERK1/2 in group I/R as compared with group S.Low perfusion pressure during the 10 min at the beginning of reperfusion significantly increased Tarlov scores,decreased apoptotic index and further increased p-Akt and pERK1/2 expression in group LP compared with group I/R.The histopathological damage in the spinal cord was attenuated in group LP.ConclusionControlled low pcrfusion pressure can reduce the spinal cord I/R injury by activating Akt and ERK1/2 and decreasing neuronal apoptosis.
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Objective To investigate the effect of splenectomy on tau expression in rat hippocampus.Methods One hundred and five male SD rats aged 6 months weighing 350-400 g were randomly divided into 3 groups: group A control (n = 15); group B anesthesia (n =45) and group C surgery (n =45). The animals were anesthetized, intubated and mechanically ventilated. In group B and C the animals were anesthetized with 1.5% isoflurane for 2 h. In group C splenectomy was performed. The animals were killed on the 1st, 3rd and 7th day after anesthesia and surgery. The hippocampi were immediately removed for determination of IL-1 and TNF-α mRNA and protein expression, expression of total tau, phosphorylated tau at Thr-205 and Ser-396 and activity of glycogen synthase kinase-3 beta (GSK-3β). Results There was no significant difference in the expression of phosphorylated tau at Thr-205 and Ser-396 between control and anesthesia groups. Surgery significantly increased the expression of IL-1β and TNF-α and induced rapid and massive hyperphosphorylation of tau at Thr-205 and Ser-396 epitope in the hippocampus and activation of GSK-3β. Conclusion Surgical trauma induces inflammatory response in hippocampus, activates GSK-3β and increases phosphorylation of tau.
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Objective To investigate the effects of acute hypervolemic hemodilution (AHH) with different fluids on blood rheology in patients with deep vein (femoral and iliac) thrombosis. Methods Thirty ASA I or II patients aged 40-64 yr who had developed deep vein thrombosis in 48 h and were scheduled for embolectomy were randomly divided into 3 groups ( n = 10 each) ; group I normal saline (NS) ; group II 6 % HES 200/0.5 ( HES) ; group IE gelofusine (GEL). AHH was performed with normal saline, 6% HES or gelofusine infusion at 20 ml·kg-1 ·h-1 for 40 min. MAP, HR and SpO2 were monitored. Blood loss, volume of blood transfusion and fluid infused and urine output during operation were recorded. Anesthesia was induced with fentanyl 3-5 fig/kg, etomidate 0.15-0.30 mg/kg, propofol 1-2 mg/kg and succinylcholine 1-2 mg/kg and maintained with 2% isoflurane and propofol infusion at 5-8 mg·kg-1·h-1 and intermittent iv boluses of vecuronium. The patients were mechanically ventilated (VT 8 ml/kg, RR 12 bpm). PaO2 and PaCO2 were maintained within normal range. Venous blood samples were obtained before and after AHH for measurement of hematocrit (Hct), whole blood viscocity (WBV) at low or high shear rates, plasma viscosity, RBC aggregation and RBC deformation. RBC aggregation index and RBC deformation index were calculated. Results MAP and HR were stable in all patients. The amount of blood transfusion and fluid infused was significantly less in group HES and GEL than in group NS. The WBV at low or high shear rates in group HES and GEL, Hct in all 3 groups and RBC aggregation index in group HES were significantly decreased after AHH, but the RBC deformation index was significantly increased in group HES. Conclusion Colloid is better than crystalloid and HES is better than gelofusine in improving intraoperative hypercoagulability and sluggish blood flow.
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Objective To investigate the risk factors for postoperative cognitive dysfunction (POCD)induced by patient-controlled intravenous analgesia(PCIA)in elderly patients. Methods 95 patients with POCD and 97 cognitive normal controls were included in the study. The cases and controls were matched for gender, type of operation and PCIA volume dose. Cognitive function was assessed by Mini-Mental-State test and the relationship between POCD and various factors was analyzed by univariate and multivariate analysis. Results Univariate analysis revealed that the education level and visual analog scale (VAS) score had significant differences between the two groups. Multivariate analysis showed that the VAS score and education level were significantly related to POCD induced by PCIA, with the odds ratios of 2. 379 (95%CI:1.205～4.698) and 0. 292 (95%CI:0.157～0.543), respectively. Conclusions Lower VAS score is an independent risk factor and higher education level seems to be a protective factor for POCD induced by PCIA.
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To identify the role of spinal cyclooxygenase (COX)-1 in the development and maintenance of postoperative pain, we examined the changes of COX-1 protein expression in lumbar spinal cord by immunohistochemistry and Western blot technique in rat plantar incision model at different time points (pre-incision or 2 h, 4 h, 6 h,12 h, 1 d, 2 d, 3 d, 5 d and 7 d after incision). We also studied the anti-allodynic effects of the COX inhibitors by intrathecal administration of non-selective COX inhibitors (ketorolac), selective COX-1 (SC-560) or COX-2 inhibitor (NS-398) immediately or 2 h, 24 h after incision. The mechanical allodynia was evaluated by using paw withdrawal threshold (PWT) response to mechanical stimulation on pre-incision, 2 h, 1 d, 2 d, 3 d, 5 d and 7 d after incision or 30 min after drug treatment. The result showed that COX-1 immunoreactive cells mainly focused in the superficial laminae of lumbar spinal dorsal horn and expression of spinal COX-1 protein increased after incision, peaked at 4 h (P＜0.01) and lasted for 12 h. Postoperative treatment with both SC-560 and ketorolac significantly alleviating the mechanical allodynia induced by skin incision, but NS-398 had no such effect. This study demonstrates that spinal COX-1 involves in the development and maintenance of postoperative hypersensitivity and intrathecal COX-1 inhibitor has anti-allodynic effect on incision pain in the rat.
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Objective To investigate the protective effect of penehyclidine hydrochloride pretreatment on focal cerebral ischemia/reperfusion injury and expression of caspase-3 in rats.Methods Sixty male Sprague-Dawley rats weighing 250-300 g were randomly divided into 3 groups(n=20): control (C) group in which sham operation was performed; ischemia-reperfusion (I-R)group, in which saline (2.0 mg?kg-1)was administered for intraperitoneal injection 30 min before anesthesia,then the ischemia model was made by occlusion of the left middle cerebral artery for 120 min; penehyclidine hydrochloride pretreatment (P) group, in which penehyclidine hydrochloride(2.0 mg?kg-1)was administered for intraperitoneal injection 30 min before anesthesia,then the same 120 min focal cerebral ischemia was performed as described in I-R group.At the end of 24 h reperfusion the animals were decapitated and the brains were removed.The volume of cerebral infarction was detected with TTC staining;Coronal sections including hippocampal tissue were obtained for HE staining.The levels of caspase-3 mRNA expression in hippocampus were detected by using semi-quantitative RT-PCR technique.Results Compared with group I-R,the volume of cerebral infarction in group P were reduced significantly(P
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Aim To investigate a possible role for nitric oxide and neurogenic pathway in the protective effect of the limb preconditioning on the ischemic-reperfusion myocardium.Methods 64 Wistar rats were randomly divided into one of the four experimental groups.In Group Ⅰ,the rats underwent 30 min occlusion of the left anterior descending coronary artery,and 120 min reperfusion.In Group PL,the rats underwent four cycles of 5 min occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group Ⅰ.In Group PL-N and Group PL-H,rats were administered with L-Nitro-Arginine Methyl Ester(L-NAME)10 mg?kg-1 or hexamethonium chloride 20 mg?kg-1,intravenously,20 min before IPC.Infarct size,as a percentage of the area at risk,was determined by triphenyltetrazolium chloride staining.And other 8 rats in each group,at the end of the experiment,all rats were killed and myocardium were stored in liquid nitrogen for the measurement of NO,NOS,iNOS and iNOS mRNA.Results The myocardial infarct size(IS)was decreased significantly in Group PL and Group PL-H compared with Group Ⅰ(P