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Objective:To explore the diagnostic accuracy of bedside ultrasound measurement of limb skeletal muscle thickness for intensive care unit-acquired weakness (ICU-AW) in patients receiving mechanical ventilation.Methods:A prospective observational study was conducted. Patients receiving mechanical ventilation admitted to the emergency ICU of Cangzhou Central Hospital from June 2018 to March 2020 were enrolled. The demographic data were collected. Medical Research Council (MRC) score was used to assess muscle strength and to determine the presence of ICU-AW once the patients were awake. The thicknesses of biceps brachii (BB), flexor carpi radialis (FCR), rectus femoris (RF) and tibialis anterior (TA) were measured by bedside ultrasound. The difference of each index was compared between the patients in ICU-AW group and in non-ICU-AW group. Receiver operator characteristic (ROC) curves were plotted to examine the values of the thicknesses of these four muscles in diagnosing ICU-AW.Results:Forty-one patients receiving mechanical ventilation (15 patients with ICU-AW, 26 patients without ICU-AW) were recruited. Compared with the non-ICU-AW group, the MRC score, the thicknesses of FCR, RF and TA were lower in the ICU-AW group [MRC score: 36 (30, 40) vs. 60 (56, 60), FCR (cm): 1.09±0.19 vs. 1.30±0.28, RF (cm): 1.57±0.58 vs. 2.23±0.58, TA (cm): 1.76±0.33 vs. 2.21±0.43, all P < 0.05], and the length of ICU stay was longer [days: 15 (9, 26) vs. 10 (4, 12), P < 0.05]. Although the thickness of BB was also lower in the ICU-AW group, there was no statistical difference between the two groups (cm: 2.45±0.57 vs. 2.70±0.61, P = 0.205). ROC curve showed that the thicknesses of FCR, RF and TA had diagnostic values for ICU-AW [area under ROC curve (AUC) and 95% confidence interval (95% CI) was 0.742 (0.582-0.866), 0.787 (0.631-0.899), 0.817 (0.665-0.920), respectively, all P < 0.01]. The thicknesses of BB couldn't diagnose ICU-AW (AUC = 0.597, 95% CI was 0.433-0.747, P = 0.296). Conclusion:The thicknesses of FCR, RF and TA measured by bedside ultrasound in patients with mechanical ventilation had diagnostic values for ICU-AW, while the thickness of BB could not diagnose ICU-AW.
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Objective@#To investigate the indications and long-term outcomes of endoscopy-assisted removal of parotid gland calculi via a transoral approach.@*Methods@#From August 2005 to December 2016, 158 consecutive patients with parotid gland calculi underwent endoscopy-assisted lithectomy transorally. They included 71 males and 87 females, with an age of 5-84 years. The immediate safety and effectiveness were evaluated. After surgery, the patients were followed up, and gland function was analyzed on the basis of clinical manifestations, sialography, scintigraphy and sialometry. Postoperative sialograms were categorized into 2 types: ①type Ⅰ, the main duct was normal or had ectasia and stenosis, but no persistent contrast was seen on the functional film; ②type Ⅱ, the main duct had ectasia or stenosis, with persistent contrast media on the functional film.@*Results@#Under one endoscopic procedure, the stones (or foreign bodies) were completely removed in 134 cases and almost completely removed in 10 cases, with a success rate of 91.1% (144/158). Of the 144 successful cases, the treatment options included direct basket retrieval or forceps grasping in 77 cases, basket entrapment with direct ostium incision in 36, basket capture with perio-ostium incision in 23 and perio-ostium incision in 8 cases with impacted stones. In two of the initial 14 failure cases, the stones were discharged spontaneously 3 months after operation. During 3-120 months′ follow-up (mean 36 months) of the 146 patients, one had recurrent stone, two developed ductal obturation, 16 had mild symptoms, and the remaining 127 cases were asymptomatic. Of the postoperative sialograms in 34 stone-free patients 25 were type Ⅰ, 9 were type Ⅱ. Both scintigraphy and saliva flow rate indicated an improvement of the affected gland function in some degree (P<0.05).@*Conclusions@#Transoral endoscopy-assisted removal of parotid gland calculi is a safe and effective technique. It is mainly indicated for mobile stones in the main duct or impacted stones in the anterior third of the Stensen′s duct. Sialography, scintigraphy and sialometry show postoperative improvement of gland function in most of the cases.
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Objective@#To investigate the different surgical approaches and long-term outcomes of endoscopy-assisted transoral removal of deep hilar and intraparenchymal stones in the Wharton′s duct.@*Methods@#From January 2008 to March 2018, 481 consecutive patients with deep hilar and intraparenchymal calculi in the Wharton′s duct underwent endoscopy-assisted transoral removal at Deparment of Oral and Maxillofacial Radiology, Peking University School and Hospital of Stomatology. There were 250 males and 231 females. Their ages ranged from 9-86 years. We operated 476 patients under local anesthesia on an outpatient basis, and the remaining 5 were operated under general anesthesia. On the basis of ultrasonography, spiral CT, sialography and endoscopy, the calculi were classified into 4 types: hilum stones (located at the hilum or proximally with a distance <5 mm from the hilum), infra-hilum stones (intra-glandular stones with a distance of 5-10 mm from the hilum), intraparenchymal stones (with a distance ≥10 mm from the hilum), and multiple stones (concomitant hilum and intra-glandular stones). The treatment approaches included: hilum duct slitting, intraparenchymal duct slitting, submandibulotomy and intraductal retrieval. The success rate, immediate safety and effectiveness of different types of stones were evaluated. After surgery, the patients were followed up, and gland function was analyzed on the basis of clinical symptoms and signs.@*Results@#The calculi sizes varied from 3 to 25 mm, with a mean of 7.8 mm. The calculi were located in the right submandibular gland in 259 patients, in the left submandibular gland in 219 patients and in bilateral glands in 3 patients. The calculi were successfully removed in 446 glands, with a success rate of 92.1% (446/484). The success rate varied according to the stone sites: 97.8% (363/371) for hilum stones, 64.4% (29/45) for infra-hilum stones, 4/16 for intraparenchymal stones and 96.2% (50/52) for multiple stones. The main treatment methods applied included hilum duct slitting in 347 glands, intraparenchymal duct slitting in 13, submandibulotomy in 4, intraductal retrieval in 73, and hilum duct slitting accompanied by intraductal retrieval in 9. Ductal breakage occurred in 2 glands. All patients complained of mild to moderate pain with a duration of 3-7 days. Nine had temporal lingual nerve injury. During 3-120 months′ follow-up (mean 36 months) of the total 484 glands, 1.6% (7/446) developed ranula, 1.3% (6/446) experienced obturation of the main duct and 2.0% (9/446) had recurrent stones. The remaining 95.1% (424/446) glands were symptom-free with good function.@*Conclusions@#Endoscopy-assisted transoral removal of deep hilar and intraparenchymal submandibular calculi is a safe and effective gland-preserving procedure. According to the depth, size and number of the calculi, variant surgical approaches should be attempted to maximize the success rate and to minimize the side effects.
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Objective@#To analyze the radiolographic features of ameloblastoma (AM), odontogenic keratocyst (OKC) and dentigerous cyst (DC) in the maxilla by spiral CT (SCT) and cone-beam CT (CBCT), and to provide useful information for the differential diagnosis of benign radiolucent lesions in the maxilla.@*Methods@#Clinical records, histopathological reports and SCT or CBCT imaging of 85 patients with primary maxillary AM, OKC or DC admitted to Peking University School and Hospital of Stomatology from December 2012 to May 2017 were collected. Radiographic characteristics including site, size, shape, cortex expansion, internal structure and effects on neighboring tissue were analyzed. For OKC and DC, the relationship between cysts and enveloped teeth was classified as centripetal, eccentric and adherent.@*Results@#The 85 patients included 56 males and 29 females, aged from 8 to 84 years old. Eighty-three patients had a single lesion, whereas 2 patients had bilateral cysts. In total, 87 lesions were analyzed, comprising 22 AM, 45 OKC and 20 DC. Among the 22 AM, 11 lesions were desmoplastic type, 16 were round-like in shape and 18 presented with buccal expansion. The shapes of the 45 OKC varied as round-like (n=26), oval (n=3), reniform (n=4), sinus-like (n=5), sinus+round (n=5) and irregular (n=2). Furthermore, 30 OKC presented with buccal expansion, 22 nearly filled the maxillary sinus and 26 were 'dentigerous'. The tooth-cyst relationship of the 'dentigerous' OKC was centripetal in 11, eccentric in 4 and adherent in 11. Among the 20 unicystic DC, 8 lesions were centripetal, 6 were eccentric and 6 were adherent type; 16 DC presented with buccal expansion.@*Conclusions@#Demosplastic type is common in maxillary AM. Most AM are round-like in shape and expand buccally. The shape of maxillary OKC varies greatly and maxillary sinus filling is common. More than a half of OKC appear 'dentigerous'. For DC and OKC, tooth-cyst relationship can be centripetal, eccentric and adherent.
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Objective To investigate the effect of ischemic postconditioning on autophagy and learning and memory impairment in rats with ischemia-reperfusion injury by P38MAPK.Methods Ninty-six rats were randomly divided into sham group ( Sham group), cerebral ischemia reperfusion group ( CIR group),cerebral ischemic postconditioning group ( CIP group) and cerebral ischemic postconditioning com-bined with SB203580 group (CIP + SB203580 group),and 24 rats in each group. The rat model of cerebral ischemia was established by Pulsinelli four-vessel occlusion. The learning and memory abilities of rats were measured by Morris water maze. HE staining were used to detect the morphological changes of hippocampal neurons. The phosphorylation of P38MAPK and Beclin-1,LC3-Ⅱexpression were observed by immunohisto-chemistry. Results Compared with the Sham group,the number of crossing the platform decreased(24 h: (3.04±0.20)times),and the escape latency was longer in CIR group(24 h:(58.38±1.52) s) (all P＜0.05). The number of survival neurons reduced (24 h:70.93±1.86),and the expression of P38MAPK,LC3-Ⅱ,Bec-lin-1 in immunohistochemistry were increased in CIR group(all P＜0.05). Compared with CIR group,the number of crossing the platform at each time point increased (24 h:(5.46±0.50)times),the escape latency was shorter (24 h:(52.42±1.53)s),the number of survival neurons increased at each time point(24 h:(83.07±5.30)) and the expression level of P38MAPK decreased in the CIP group,while the expression lev-el of LC3-II,Beclin-1 increased (all P＜0.05).Compared with the CIP group,the number of crossing the plat-form((24 h:(7.13±0.33)times),the escape latency was shorter (24 h:(48.04±1.39)s),the number of survival neurons increased at each time point(24 h:(91.40±1.74)),and the expression of P38MAPK was down-regulated,while the expression of LC3-II,Beclin-1 were up-regulated in CIP +SB203580 group(all P＜0.05). Conclusion Ischemic postconditioning can improve learning and memory impairment in rats with is-chemia-reperfusion injury by P38MAPK regulating autophagy.
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Objective To investigate the status quo of utilization of chronic disease resources and quality of life in chronic obstructive pulmonary disease (COPD) patients,and explore the correlation between them.Methods A total of 394 patients with COPD were investigated by the general information question,the Chronic Illness Resources Survey and COPD Assessment Test (CAT).Results The CAT score of COPD patients was (21.33 ± 7.14) points.Among 394 COPD patients,63 patients (16.0％) had ideal utilization of chronic disease resources,and 331 patients (84.0％) did not,the highest dimension of each dimension score was 3.33 points for the health care team (interquartile range 2.67-3.67 points),and the lowest score was 1.67 points for the organization (interquartile range 1.00-2.00 points).Except media policy and quality of life were not relevant,all other dimensions were negatively correlated with CAT scores in COPD patients (r=-0.368--0.169,all P＜0.05).Linear regression analysis showed that the factors affecting the quality of life of COPD patients were:health care team,family and friends,individual coping (P＜0.05).Conclusions COPD patients with quality of life and chronic disease resources should be improved,medical staff should pay more attentions to patients in communication and guidance,and encourage the support of family and friends,in particular,pay attentions to patients with poor attitude,thus improving the quality of life of patients.
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Objective:To investigate the effects of cerebral ischemic postconditioning (CIP)on the expressions of Cyclin D1 and CDK4 proteins in hippocampal neurons of the rats with global cerebral ischemia and reperfusion (I/R)based on Notch1 signaling pathway,and to explore the mechanisms.Methods:A total of 128 healthy male SD rats were randomly divided into sham operation group,I/R group (modified Pulsinelli four vessel occlusion method), CIP group (repeated 3 times of reperfusion or blocking blood vessel before complete reperfusion)and DAPT group (intraperitoneal injection of 10 mg·kg-1 ·d-1 DAPT 3 h before CIP),and there were 32 rats in each group.HE staining was used to observe the morphology of the neurons at 6, 24, 48 and 72 h after ischemia;immunohistochemical staining was used to observe the expressions of Cyclin D1, CDK4 and Notch1 in the hippocampus of the rats;Western blotting method was used to observe the expression levels of Cyclin D1,CDK4 and Notch1 proteins in the hippocampus of the rats at different time points. Results:The HE staining results showed that compared with sham operation group,the structure of neurons in hippocampus area of the rats in I/R group was damaged and the survival rate of neurons was significantly decreased (P <0.05).Compared with I/R group,the survival rates of neurons in the hippocampus area of the rats in CIP group were significantly increased at the corresponding time (P <0.05).Compared with CIP group,the survival rates of neurons in hippocampus area of the rats in DAPT group at the corresponding time were significantly decreased (P < 0.05 ). The immunohistochemical staining results showed that compared with sham operation group,the number of cells with positive Notch1,Cyclin D1 and CDK4 in I/R group was increased (P < 0.05).Compared with I/R group,the number of Cyclin D1 and CDK4 positive cells in CIP group was decreased (P <0.05),and the number of Notch1 positive cells of was significantly increased (P <0.05).Compared with CIP group,the number of Cyclin D1 and CDK4 positive cells in DAPT group was increased (P < 0.05 ),and the number of Notch1 positive cells was significantly decreased (P < 0.05 ). The Western blotting results showed that compared with sham operation group,the expression levels of Notch1,Cyclin D1 and CDK4 proteins in the hippocampus of the rats in I/R group were increased (P <0.05);compared with I/R group,the expression levels of Cyclin D1 and CDK4 proteins in the hippocampus of the rats in CIP group were significantly decreased (P <0.05),and the expression level of Notch1 protein in the hippocanpus of the rats was significantly increased (P < 0.05 ); compared with CIP group,the expression levels of Cyclin D1 and CDK4 proteins in the hippocampus of the rats in DAPT group were increased (P <0.05),and the expression level of Notch1 protein was significantly decreased (P < 0.05).Conclusion:CIP may play an important role in protecting the neurons by increasing the activity of Notch1 and inhibiting the expressions of Cyclin D1 and CDK4.
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Objective To investigate the clinical efficacy of apapatinib-targeted therapy combined with oxaliplatin and tiggio for treatment of gastric cancer. Methods A total of 150 patients with advanced gastric cancer were enrolled from March 2015 to March 2017. According to the random number table method, the patients were divided into the study group (apocitinib combined with oxaliplatin+tiggio) and the control group (oxaliplatin + tiggio), 75 cases each. The recent treatment effects and adverse reactions were compared between the two groups. Results The objective response rate (46.7 % vs. 25.3 %) and disease control rate (76.0 % vs.48.0 %)in the study group and the control group were statistically significant(all P <0.05).There were no statistical differences in the incidence of complications such as myelosuppression, digestive tract reaction, fatigue and oral ulcer between the two groups (all P > 0.05). The incidence of complications such as hypertension, proteinuria and hand-foot syndrome in the study group was higher than those in the control group (all P < 0.05), but it was in a state of grade Ⅰ~Ⅱ and tolerance. Conclusion Apotiphene combined with oxaliplatin and tiggio as a chemotherapy regimen for advanced gastric cancer may have a better effect.
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Objective To explore the mechanism of ischemic postconditioning in relieving cerebral ischemia reperfusion (IR) by regulating autophagy through P38MAPK pathway.Methods Cerebral ischemia reperfusion model was established by using modified Pulsinelli four-vessel occlusion (4-VO).Totally 128 male SD rats were divided into 4 groups randomly:control group (sham),cerebral ischemia reperfusion model group (CIR),cerebral ischemic postconditioning group (CIP),and cerebral ischemic postconditioning + P38MAPK inhibitor group (SB203580 group).Each group was subdivided into four time points:6 h,24 h,48 h,and 72 h.The morphological changes of the hippocampus CA1 area neurons at each time point and the number of surviving nerve cells were detected with HE staining.The expression of the hippocampus CA1 area phosphorylated P38MAPK and the autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with immunohistochemistry.The protein content of the hippocampus phosphorylated P38MAPK and autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with Western blotting.Results Compared with those in sham group,the damage of rats' hippocampal neuron structure and the survival rate of neurons at each time point decreased in CIR group,the expressions of p-P38MAPK,LC3-Ⅱ and Beclin-1 increased.Compared with those in CIR group,in CIP and SB203580 groups the structure of rats hippocampal neurons was improved,the survival rate of neurons increased,the expression of p-P38MAPK decreased and the expressions of LC3-Ⅱ and Beclin-1 increased at each time point.Compared with CIP group,SB203580 grouphad improved structure of rats' hippocampal neurons,increased survival rate of neurons,decreased expression of p-P38MAPK,and increased expressions of LC3-Ⅱ and Beclin-1 at each time point.Conclusion Cerebral ischemic postconditioning through inhibiting P38MAPK pathway can regulate autophagy and exert its nerve-protective effect.
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Objective To investigate the changes in the expression of phosphatidylinositol 3?kinase(PI3?K),mammalian target of rapamycin (mTOR)and Beclin?1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion ,so as to explore the role of PI3K/mTOR/autophagy pathway in global cerebral ischemia/reperfusion injury aggravated by intermittent hypoxia. Methods A total of 80 healthy male Wistar rats were randomly divided into sham operation group(SO group,n=20),merely ischemia/reperfusion group(I/R group,n=20),intermittent hypoxia for 7?day ischemia/reperfusion group(IH7+I/R group,n=20),and intermittent hypoxia for 21?day ischemia/reperfusion group(IH21+I/R group,n=20). IH7+I/R group and IH21+I/R group were respectively given intermittent hypoxia for 7 days and 21 days before ischemia/reperfusion. The cerebral ischemia/reperfusion model was established by modified Pulsinelli four?vessel occlusion method. The morpholog?ical changes of nerve cells in hippocampal CA1 region were observed by HE staining and electron microscope. The protein expressions of PI3?K, mTOR and Beclin?1 of nerve cells in hippocampal CA1 region were detected by immunohistochemical staining and RT?PCR. The learning memory capacity of rats were assessed by the Morris water maze test. Results Compared with SO group,I/R group increased the never cells morphology damages,reduced the number of survival neurons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell,mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in I/R group compared with S0 group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in I/R group compared with S0 group(P<0.05). Compared with I/R group,intermittent hypoxia groups increased the never cells morphology damages,decreased the number of survival neu?rons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell, mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05),and the changes were more significant in IH21+I/R group(P<0.05). Conclusion Intermittent hypoxia can aggravate neurological injury after ischemia,which is related to PI3K/mTOR/autophagy pathway activation.
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Objective To explore the regulation of PI3K-mTOR signaling pathways on autophagy of hippocampus nerve cells after subarachnoid hemorrhage (SAH)in rats.Methods We randomly divided 72 male Sprague-Dawley rats into sham group,SAH model group and LY294002 group with 24 rats in each group.We established SAH model with the secondary injection of blood method while the sham group was not injected with blood.PI3K signaling pathways specific inhibitor LY294002 was injected with 500μmol per rat 30 minutes before modeling.After 6,24,72 and 144 h morphologic changes of hippocampus CA1 neural cells were observed by microscopy;the expression levels of PI3K,mTOR,Beclin-1 and LC3-Ⅱ were detected by immunohistochemical method.Results The density of survival neurons in the SAH group was significantly lower than that in the control group (P<0.05),PI3K-mTOR signaling pathways were activated obviously,and the expressions of Beclin 1 and LC3-Ⅱ were significantly higher than those in the control group (P<0.05 ).The number of survival neurons significantly decreased in the LY294002 group compared with the SAH group at each time point (P<0.05),PI3K-mTOR signaling pathways were suppressed.The expressions of Beclin-1 and LC3-Ⅱ were significantly lower than those in the SAH group (P<0.05).Conclusion PI3K-mTOR signaling pathways protect neurons by activating the autophagy of neurons after SAH.
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Objective Moderate autophagy helps improve the viability of neurocytes.This study aims to investigate the effect of SP600125 on the autophagy and loss of nerve cells in the hippocampus in rats with subarachnoid hemorrhage (SHA).Methods Forty healthy male SD rats were equally randomized into a sham operation, an DMSO group, an SAH model, and an SP600125 group.The SAH model was established by vascular puncture and the rats of the SP600125 group were injected with 10 μL of SP600125 (3 μg/μL) into the lateral cerebral ventricle at 30 minutes before modeling.Sham group and SAH group were injected with equal volume of normal saline, DMSO group was injected with the same amount of DMSO.The animals were sacrificed at 24 hours after modeling for observation of the changes in the morphology and the number of neurons in the hippocampus by HE staining and qualitative and quantitative determination of the expressions of the p-JNK protein and the autophagy markers beclin-1 and LC3-II by immunohistochemistry and Western blot.Results Compared with the sham operation group, the neurons exhibited a disordered arrangement and the cells were polygonal and decreased in number in the hippocampus of the SAH models, while milder neuronal injury and more cells were observed in the rats of the SP600125 group than in the SAH models.The mean optical density values of Beclin-1, LC3-II and p-JNK in the hippocampus were significantly higher in the SAH models (14.66±4.40, 12.62±3.46, and 12.82±3.68) and DMSO (13.85±3.85、11.59±4.52、13.03±3.53), and the SP600125 group (9.86±3.14, 6.78±2.56, and 5.60±2.42) than in the sham operation group (1.56±0.28, 1.60±0.30, and 1.58±0.32) (P<0.05), but markedly lower in the SP600125 than in the SAH model group (P<0.05).The expressions of Beclin-1, LC3-II and p-JNK were remarkably increased in the SAH models (0.474±0.122, 0.668±0.130, and 0.496±0.124) and DMSO (0.432±0.102、0.628±0.113、0.416±0.094) and the SP600125 group (0.264±0.106, 0.332±0.113, and 0.219±0.104) than in the sham operation group (1.56±0.28, 1.60±0.30, and 1.58±0.32) (P<0.05), but significantly decreased in the SP600125 group as compared with the SAH models (P<0.05).Conclusion SP600125 has a protective effect on the neurocytes in the hippocampus of SAH rats, which may be associated with SP600125 moderately activating neuronal autophagy by inhibiting the activity of the JNK signaling pathway.
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Objective To study the risk factors for cognitive impaurment in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with ischemic stroke.Methods Three hundred and twenty-eight OSAHS patients with ischemic stroke were divided into cognitive impairment group (n=158) and cognitive impairment-free group (n=170) according to their MMSE score.The risk factors for their cognitive impairment were analyzed by multivariate logistic regression analysis and stratification analysis respectively.Results The blood glucose and lipid,AHI,LSaO2,infarction size and site,HIF-1 and Ngb level were significantly different between the two groups (P＜0.01).Multivariate logistic regression analysis showed that blood glucose and lipid,AHI,infarction site and Ngb level were the independent risk factors for cognitive impairment (OR=3.527,95％CI:1.559-7.983,P=0.002;OR=6.413,95 ％CI:2.766-14.865,P=0.000;OR=4.099,95％CI:1.694-9.918,P=0.002;OR=4.484,95％CI:1.950-10.310,P=0.000;OR=3.891,95 ％CI:1.759-8.606,P=0.001).Stratification analysis showed that high HIF-1 and Ngb levels were positively related with cognitive impairment in patients with AHI＞20 times/h,frontotemporal infarction,hyperglycosemia or hypoglycosemia,and dyslipidemia.Conclusion High HIF-1 and Ngb levels are independently related with cognitive impairment in OSAHS patients with ischemic stroke.
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Objective To investigate synergistic effects of extracellular signal regulated kinase (ERK1/2) and phosphatidylinositol 3 kinase (PI3-K) pathway inhibitors on autophagy in the hippocampus of rats with subarachnoid hemorrhage (SAH),for identification of therapeutic targets in SAH.Methods Totally,200 male SD rats were randomly divided into a sham operated group,SAH group,inhibitor U0126 group,inhibitor LY294002 group,and a U0126+ LY294002 group.Animal models were established by injecting autologous blood twice into the cisterna magna.Morphological changes in the hippocampus nerve cells were detected by HE staining;ERK1/2,PI3-K,beclin-1,and LC3 mRNA expression in the hippocampus were detected by real-time PCR,and phosphorylated ERK 1/2,PI3-K,beclin-1,and LC3-Ⅱ protein expression were detected by immunohistochemistry.Results Neuronal death rate and phosphorylated ERK1/2,PI3-K,beclin-1,and LC3-Ⅱ levels in the hippocampus in the SAH group were higher than in the sham group (all P ＜ 0.05).Neuronal death rate in U0126 or LY294002 group was higher than in SAH group,while ERK1/2,PI3-K,beclin-1,and LC3 mRNA and phosphorylated ERK 1/2,PI3-K,beclin-1,and LC3-Ⅱ protein levels were lower than in SAH group (all P ＜ 0.05).Neuronal death rate in U0126 +LY294002 group was higher than in U0126 or LY294002 group,while ERK1/2,PI3-K,beclin-1,LC3 mRNA and phosphorylated ERK 1/2,PI3-K,beclin-1,and LC3-Ⅱ protein levels in the hippocampus were lower than in U0126 or LY294002 group (all P ＜ 0.05).Conclusion Co-targeting the inhibition of ERK 1/2 and PI3-K pathways can significantly reduce neuronal cell autophagy and aggravate cells loss after SAH.
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Objective To assess the effect of ischemic postconditioning on the Notch1 signaling pathway,and learning and memory in rats with global cerebral ischemia.Methods A total of 128 healthy male SD rats were randomly divided into the sham operation (sham),whole-brain ischemia(CIR),ischemic treatment(CIP),and inhibitor(DAPT) groups,with 32 rats in each group.A global cerebral ischemia model was generated using the modified Pulsinelli's four-vascular occlusion model,and the inhibitor group was injected intraperitoneally with gamma secretase inhibitors (DAPT) before ischemic treatment.Rats' learning and memory function results from the Morris water maze test were assessed by observing the changes in hippocampal CA1 neurons with HE staining.The expression of Notch1 in the CA1 area of the hippocampus was assessed using immunohistochemical and Western blotting methods in rats.Results Compared with the sham group,the hippocampal cell survival rate in the CIR group decreased significantly (P ＜ 0.05) and the expression level of Notch1 increased significantly (P ＜ 0.05).Compared with the CIR group,the CIP group revealed a significantly higher hippocampal cell survival rate (P ＜ 0.05) and an increase in Notch 1 expression (P ＜ 0.05);compared with the CIP group,the hippocampal cell survival rate significantly decreased after DAPT administration (P ＜ 0.05) and Notch1 expression decreased significantly.Conclusion Ischemic postconditioning can promote the recovery of learning and memory ability,which may relate to the activation of the Notch 1 signaling pathway.
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ABSTRACT:Objective To explore role of U0126,the specific inhibitor of ERK signaling pathway,in early brain injury (EBI)and the autophagy of nerve cells in hippocampus area in subarachnoid hemorrhage (SAH). Methods A total of 48 male adult SD rats were randomly divided into control group,SAH group,DMSO+SAH group,and U0126+SAH group,with 12 in each.We established SAH rat model by the puncture of internal carotid artery.The same amount of saline water,DMSO and U0126 solution of 0.5 mL per rat was injected respectively into the rats of different groups 30 min before modeling.The rats were killed at 24 h.To measure brain water content by Wet and dry method after 24 h,the morphological changes of hippocampus CA1 neural cells were observed by microscopy;the expression levels of ERK,Beclin-1 and LC3 were detected by using immunohistochemical method. Results Compared with that in sham group,brain water content increased obviously in SAH model group.The density of surviving neurons in SAH group was significantly lower than that in control group (P<0 .0 5 ).ERK signaling pathway was activated obviously,the expressions of Beclin 1 and LC3-Ⅱ were significantly higher than those in control group (P<0.05).Compared with SAH model group,in U0126 group brain water content increased obviously.Compared with those in SAH group,the density of surviving neurons was significantly lower (P<0.05), ERK signaling pathway was suppressed,the expressions of Beclin-1 and LC3-Ⅱ were significantly lower (P<0.05). Conclusion The U0126,the ERK signaling pathway inhibitor,can inhibit neuron autophagy and increase EBR of SAH.
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Objective To investigate the effect of MAPK activation on autophagy in the hippocampus of rats with subarachnoid hemorrhage.Methods A total of 100 male SD rats were divided into 5 groups randomly:sham operated group,SAH group,inhibitor U0126 group,inhibitor SB203580 group,SP600125 group.The animal model was established by injecting the autologous blood into cisterna magna twice.The morphological changes of hippocampus nerve cells of rat brain were detected with HE.The mRNA levels of ERK1/2,p38MAPK,JNK and LC3 in hippocampus were detected with quantitative real time PCR and the expression of phosphorylated ERK1/2,phosphorylated p38MAPK,phosphorylated JNK and LC3-Ⅱ in hippocampus of rat brain were detected by immunohistochemistry.Results Compared with the Sham group,the survival rate of neurons in SAH group decreased (6 h:(84.982 ± 5.723) ％,24 h:(74.383± 9.860) ％,48 h:(62.860± 10.820) ％,72 h:(52.260± 10.960) ％) (all P＜0.05).The levels of ERK1/2 mRNA,p38MAPK mRNA,JNK mRNA and LC3 mRNA in hippocampus increased (all P＜ 0.05) and the expression of p-ERK1/2,p-p38MAPK,p-JNK,LC3-Ⅱ proteins increased(all P＜0.05).Compared with the SAH group,the survival rate of neurons in U0126 group was decreased (6 h:(71.620±6.542) ％,24 h:(66.221±7.742)％,48 h:(55.208±8.802) ％,72 h:(46.242±7.782) ％),and the ERK1/2 and LC3 in hippocampus decreased both in mRNA level and in protein level(all P＜0.05).Compared with the SAH group,the survival rate of neurons in SB203580 groups was increased (6 h:(89.082±6.602)％,24 h:(85.840±9.726) ％,48 h:(74.96± 10.916) ％,72 h:(69.211 ± 10.745) ％),and the p38MAPK,LC3-Ⅱ in hippocampus decreased at both mRNA and protein levels (all P＜0.05).Compared with the SAH group,the survival rate of neurons in SP600125 groups was increased (6 h:(91.620± 7.542) ％,24 h:(86.221 ± 10.742) ％,48 h:(75.208±11.802) ％,72 h:(70.242± 11.782) ％).The expression of JNK was decreased while the LC3-Ⅱ was increased in hippocampus (P＜0.05).Conclusion MAPK activation is involved in the autophagy of hippocampal neurons after SAH,in which ERK1/2 activation plays a positive role in the regulation of autophagy in hippocampal neurons after SAH,while p38MAPK and JNK activation plays a negative role in autophagy.
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Objective To investigate the relationship of extracellular regulated protein kinases activation and neural cells autophagy in rats after subarachnoid hemorrhage.Methods One hundred twenty male SD rats were randomly divided into sham operated group,SAH group,ERK1/2 inhibitor U0126 group,autophagy inducer rapamycin (Rap) group.The animal models were established by injecting the autologous blood into cisterna magna twice.U0126 (5μ g/μL) and Rap (10nmol/μL) were injected into lateral ventricles in U0126 group and Rap group 30min before SAH.The morphology of hippocampal nerve cells were examined by using light microscopy.The expression levels of phosphorylated ERK 1/2 (p-ERK 1/2),ERK 1/2mRNA and autophagy markers (Beclin-1 and Beclin-1 mRNA、LC3-Ⅱ and LC3mRNA) in the hippocampus were detected by using inmunohistochemistry and real-time fluorescence quantitative PCR.Result Compared with sham group,the rate of dead nerve cells,the mRNA levels of ERK1/2,Beclin-1 and LC3 as well as the levels of the p-ERK1/2,Beclin-1 and LC3-Ⅱ increased in SAH group (P＜0.05).Compared with SAH group,the rate of dead nerve cells increased(P＜0.05),the ERK1/2 mRNA,Beclin-1 mRNA and LC3 mRN A,and p-ERK1/2,Beclin-landLC3-Ⅱ in U0126 group decreased(P＜0.05);the rate of dead nerve cells decreased (P＜0.05),the Beclin-1 mRNA and LC3 mRNA,the Beclin-1and LC3-Ⅱ level increased in Rap group(P＜0.05),but ERK 1/2 mRNA and p-ERK 1/2 remained unchanged (P＞0.05).Conclusion Activation of the ERK1/2 signaling pathway after SAH,can induce nerve cells death by increasing Beclin-1 and LC3-Ⅱ expressions.
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Objective To investigate the effect of BQ-123 on the ability of learning and memory and nerve cell autophagy in hippocam-pus in rats with subarachnoid hemorrhage (SAH). Methods 72 male Sprague-Dawley rats were randomly divided into sham group, SAH model group (SAH group) and BQ-123 group with 24 rats in each group. SAH model was established by injecting the autologous blood into cisterna magna twice. The sham group was not injected blood. BQ-123 group received intracerebroventricular injection with BQ-123 18μg 30 minutes before modeling. 6, 24, 72 and 144 hours after modeling, the passive avoidance latency (PAL) and active avoidance reaction rate (AARR) were tested with Shutter Box Test, the nerve cell morphological changes of hippocampus were observed with HE staining, and the expressions of Beclin-1 and LC3-II were detected with immunohistochemical staining. Results Compared with the sham group, the PAL pro-longed, the AARR decreased (P<0.05), the nerve cells in the hippocampus reduced (P<0.05), and the expressions of Beclin-1 and LC3-II in-creased (P<0.05) in SAH group. Compared with SAH group, PAL shortened (P<0.05), AARR increased (P<0.05), the nerve cells in the hip-pocampus increased (P<0.05), and the expressions of Beclin-1 and LC3-II increased (P<0.05) in BQ-123 group. Conclusion BQ-123 can promote the recovery of learning and memory ability, which may relate to the activation of nerve cell autophagy in the hippocampus.
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Objective To observe the effect of aerobic exercise preconditioning on growth-associated protein-43 (GAP-43) and Nogo-A in rats after cerebral ischemia/reperfusion. Methods Sprague-Dawley rats were equally divided into sham group (n=40), cerebral ischemia/reperfusion group (n=40) and aerobic exercise preconditioning group (n=40), and global cerebral ischemia model was formed with modified four-vessel occlusion. The rats was sacrificed six hours, one day, three days and seven days after ischemia, respectively. The hippocampus neural cells were observed in five rats with HE staining and immunohistochemistry of GAP-43 and Nogo-A, and the other five rats were test-ed with RT-PCR of GAP-43 and Nogo-A. Results Compared with those in the cerebral ischemia/reperfusion group, the apoptotic neurons and expression of GAP-43 significantly increased all the time points in the aerobic exercise preconditioning group (P<0.01), while the ex-pression of Nogo-A decreased (P<0.01). Conclusion Aerobic exercise preconditioning can promote the regeneration of neuronal cells and axon after cerebral ischemia/reperfusion injury, which is related to the regulation of GAP-43 and Nogo-A.