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The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed. One Sentence SummaryThe novel SARS-CoV-2 Omicron variant, though less pathogenic, is highly transmissible and outcompetes the Delta variant under immune selection pressure in the golden Syrian hamster COVID-19 model.
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BackgroundVaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. MethodsSince mucosal immunity is critical for nasal prevention, we investigated an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. FindingsSubstantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. InterpretationOur results demonstrated that intranasal influenza-based boost vaccination is required for inducing mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. FundingThis study was supported by the Research Grants Council Collaborative Research Fund (C7156-20G, C1134-20G and C5110-20G), General Research Fund (17107019) and Health and Medical Research Fund (19181052 and 19181012) in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program (JSGG20200225151410198); the Health@InnoHK, Innovation and Technology Commission of Hong Kong; and National Program on Key Research Project of China (2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); and donations from the Friends of Hope Education Fund. Z.C.s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).
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BackgroundObservational studies showed that coronavirus disease 2019 (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). Whether COVID-19 is causally related to increasing susceptibility and severity of atrial fibrillation (AF), the main form of CVD, remains still unknown. MethodsThe study aims to investigate the bidirectional causal relations of COVID-19 with AF using two-sample Mendelian randomization (MR) analysis. ResultsMR evidence suggested genetically predicted severe COVID-19 was significantly associated with higher risk of AF (odds ratio [OR], 1.041; 95% confidence interval (CI), 1.007-1.076; P = 0.017), while genetically predicted AF was not causally associated with severe COVID-19 (OR, 0.831; 95% CI, 1.619-1.115; P=0.217). There was limited evidence to support association of genetically proxied COVID-19 with risk of AF (OR, 1.051; 95% CI, 0.991-1.114; P=0.097), and vice versa (OR, 0.163; 95% CI, 0.004-6.790; P=0.341). MR-Egger indicated no evidence of pleiotropic bias. ConclusionOverall, severe COVID-19 may causally affect AF through independent biological pathway. Survivors from severe COVID-19 might be of high risk of AF in the future.
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SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.
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SARS-CoV-2 contains a PRRA polybasic cleavage motif considered critical for efficient infection and transmission in humans. We previously reported that virus variants with spike protein S1/S2 junction deletions spanning this motif are attenuated. Here we characterize a further cell-adapted SARS-CoV-2 variant, Ca-DelMut. Ca-DelMut replicates more efficiently than wild type or parental virus in cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut does not induce proinflammatory cytokines in hamster infections, but still triggers a strong neutralizing antibody response. Ca-DelMut-immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, demonstrating sterilizing immunity.
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Objective To explore the effects of target value management for quality control indexes in chest pain center on the efficiency and effectiveness of in-hospital treatment for STEMI patients.Methods The database of Chest Pain Center in General Hospital of Guangzhou Military Command was retrospectively analyzed.STEMI patients who visited our hospital from March 2011 to March 2018 were selected as the research subjects.During the review period,the target values of quality control indexes were adjusted 4 times.Before and after the 4 adjustment,the efficiency indexes of in-hospital treatment STEMI patients were compared,including the first medical contact to the first electrocardiogram (FMC2ECG) time,catheter lab activation time and Door-to-Balloon (D2B) time.Length of hospital stay,in-hospital mortality and hospitalization cost were compared as well.Results A total of 332 STEMI patients were included in the study.As the quality control target values became stricter,the median and the average value of FMC2ECG time,catheter lab activation time and D2B time showed a downward trend.Among these data,the D2B time decreased from 95 (74,134.5) min to 50 (44.5,71) min,and its differences were of the most significance.However,there is no significant difference in the hospitalization cost,length of hospital stay and in-hospital mortality of STEMI patients.Conclusions The target value management of quality control indexes can improve the in-hospital treatment efficiency for STEMI patients,but the improvements of treatment efficiency and effectiveness cannot be immediately revealed.It takes a certain amount of time and needs enough cases to reach a significant difference.
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The German ( Kooperation für Transoarenz und Qualit?t im Gesundheitswesen, KTQ) certification system was officially launched in Germany in December 2001. Over ten years′ development proves that the KTQ certification system as a high standard medical management system. The authors introduced its background, the update of certification content and procedures, and explained its characteristics and advantages.These insights provide valuable references for establishing a professional and efficient quality certification system, suitable for China′s social and economic development level.
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Objective To study the value of 256 spiral CTA and DSA in diagnosis of carotid artery stenosis (CAS) and cerebral collateral circulation in acute ischemic stroke (AIS) patients.Methods The imaging data of 256 spiral CTA and DSA in 30 AIS patients were retrospectively analyzed.The sensitivity,specificity and consistency of 256 spiral CTA and DSA in diagnosis of CAS and cerebral collateral circulation were compared.Results The consistency rate of 256 spiral CTA and DSA was 82.8％ in diagnosis of CAS,especially in diagnosis of severe stenosis (κ=0.75).Cerebral collateral circulation was detected in 18 patients by 256 spiral CTA and in 19 patients by DSA with a consistency of 90 ％.Cerebral collateral circulation was detected in 40 by CTA and in 43 by DSA out of the 330 collateral arteries with a high consistency (κ=0.925,0.894).Conclusion The consistency of 256 spiral CTA and DSA is very high in diagnosis of CAS and cerebral collateral circulation in AIS patients.
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Objective To explore the effect of general anesthesia on Wuzhishan miniature pigs induced by a mixture of ketamine, Sumianxin II and midazolam, and maintained by ketamine and propofol in surgery lasting up to 8 hours. Methods A total of 18 Wuzhishan miniature pigs (body weight (20. 3 ± 1. 9) kg, 14 male and 4 female) were used in this study. The induction of anesthesia was performed with intramuscular injection of ketamine (8 -10 mg/kg) Sumianxin II (1. 5 mL) and midazolam (10 mg) behind the ear, and the general anesthesia was maintained with a mixture containing 0. 9％ sodium chloride 8 mL, ketamine 100 mg/2 mL and propofol 200 mg/40 mL, continuously injected through the marginal ear vein through a syringe infusion pump. The time spent for anesthesia induction and the duration time of anesthesia were recorded. Physiological indexes including body temperature, blood pressure, heart rate and respiratory rate, the reflex activities, and the effects of analgesia, sedation and muscular relaxation of the miniature pigs under anesthesia at 0, 0. 5, 1, 1. 5, 2, 4, 6, 8 h were observed. Results All the 18 pigs were successfully anaesthetized, but 4 pigs died during surgery due to hypovolemic shock, anesthesia accident, left main coronary thrombosis and reperfusion arrhythmia, respectively. During anesthesia, the analgesia, sedation and muscular relaxation effects on the pigs were obvious. The average time spent for anesthesia induction was (4. 8 ± 1. 2) min and the duration time of anesthesia was (54. 1 ± 5. 8) min. The eyelid reflex, corneal reflex and anal reflex in the pigs were weak or disappeared during 1 -8 h after the anesthesia was induced. The body temperature of the pigs was decreased gradually, with a significant difference between 1 h and 0 h (P＜ 0. 05), reaching the lowest point at 4 h, and then maintained stable. The blood pressure was gradually decreased, reaching the lowest level at 2 h (P ＜ 0. 05), then somehow increased, and maintained at a stable level until the end of surgery. The respiratory rate fluctuated during the anesthesia, with no significant difference. Conclusions The anesthesia induced by a combination of ketamine, Sumianxin II and midazolam and maintained with a combination of ketamine and propofol is simple to operate, shows effects fast, and has good effects of analgesia, sedation and muscular relaxation, keeping the circulatory system and respiratory system relatively stable throughout the anesthesia. Thus it is suitable for general anesthesia for miniature pigs.
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Objective: To comprehensively evaluate the quality of Radix et Rhizoma Rhei based on gray correlationalanalysis and functional components, and to explore the difference of Radix et Rhizoma Rhei in different genuineproducing areas. Methods: HPLC was utilized to analyze 14 main compositions contained in the samples, includingemodin, rhein, chrysophanol, aloe-emodin, physcion, rheinoside, physcion glucoside, chrysophan, aloe-emodinglucoside, emodin methyl glycoside, sennoside, sennoside B, catechin and gallic acid. Then python 2.7 software wasemployed for gray correlation analysis of functional components closely related to the traditional efficacy of Radix et Rhizoma Rhei. Results: The qualities of Radix et Rhizoma Rhei grow in different areas were different. Tanggute Radix et Rhizoma Rhei grew in Tianzhu Gansu had the best effects of "expelling water retention and attacking the accumulation", and that grew in Yajiang Sichuan had the best effects of "clearing heat and removing toxin". Zhangye Radix et Rhizoma Rhei grew in Lixian Gansu had the best effect of"expelling stasis and unblocking the channels". Conclusion: Patternrecognition has broad prospects in the field of quality evaluation of traditional Chinese medicine. From the clinicalefficacy of traditional Chinese medicine, pattern recognition at the level of efficacy components can provide a new ideafor establishing a more complete and scientific quality evaluation system for traditional Chinese medicine.
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@#Objective To observe the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in substantia nigra in rats with Parkinson's disease (PD). Methods A total of 96 Sprague-Dawley rats were randomly divided into sham group, model group, PI3K inhibitor LY294002 group and mTOR inhibitor rapamycin group. Each group was divided into 4 days and 8 days subgroups after the model. PD model was established by injecting rotenone subcutaneously. The expres-sion of PI3K, p-Akt and p-mTOR in substantia nigra was detected with immunohistochemistry and Western blotting. Results Compared with the sham group, the expression of PI3K, p-Akt and p-mTOR increased in the model group (P<0.05), and was more in 8 days subgroup than in 4 days subgroup (P<0.05). Compared with the model group, the expression of p-Akt and p-mTOR reduced in the LY294002 group (P<0.05), while the expression of PI3K varied little (P>0.05);the expression of p-mTOR decreased in the rapamycin group (P<0.05), while the expression of PI3K and p-Akt varied little (P>0.05). Conclusion PI3K/Akt/mTOR signaling pathway is over activated in substantia nig-ra in rats with Parkinson's disease, which may play an important role in occurrence and development of the disease.
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Objective To explore the influencing factors of the collateral circulation formation in patients with acute cerebral infarction.Methods Three hundred and fifty-two patients with acute cerebral infarction were included in this study,the clinical date of their head and neck 256 slice spiral CT angiography (CTA)examination was analyzed.According to the formation of collateral circulation in the head and neck CTA imaging results,it is divided into the collateral circulation group and the non-collateral circulation group.The clinical data of the two groups were compared.The influencing factors of the formation of collateral circulation in patients with acute cerebral infarction were analyzed by single factor analysis and multivariate logistic regression analysis.Results (1)In 352 cases of acute cerebral infarction,197 cases(56.0%)had collaterals,155 cases (44.0%)had none collateral.(2)Single factor analysis showed that age(t=-2.860,P=0.004),hypertension combined with diabetes(χ2 = 10.709,P= 0.001),history of TIA(χ2 = 4.626,P= 0.034),low density lipoprotein(t=-2.176,P=0.030),high homocysteine(t=2.885,P=0.004),cerebral vascular stenosis(Z=-5.936,P=0.000),posterior circular lesions(χ2=8.548,P=0.004)were the influencing factors in the formation of collateral circulation.(3)Multivariate Logistic regression analysis showed that old age(OR=1.031;95%CI=1.008-1.054;P=0.007),hypertension combined with diabetes(OR= 2.009;95%CI=1.159-3.482;P=0.013),high homocysteine(OR=1.023;95%CI,1.005-1.041;P=0.014),circular lesions(OR=1.727;95%CI=1.063-2.804;P=0.027)were relatively independent risk factors in acute cerebral infarction patients with none circulation,the degree of cerebral vascular stenosis(OR=0.507;95%CI=0.389-0.661;P=0.000),low density lipoprotein(OR=0.723;95%CI=0.532-0.982;P=0.038)served as protective factor.Conclusion Old age,hypertension combined with diabetes,high homocysteine and posterior circulation lesions are risk factors for the formation of collateral circulation in patients with acute cerebral infarction,cerebral vascular stenosis degree and low density lipoprotein can promote the formation of collateral circulation.
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Objective@#To observe the clinicopathologic features and prognosis of prostate cancer (PCa) in young men.@*Methods@#Twenty-eight early onset (≤55 years) patients with PCa pathologically confirmed in the Peking University Third Hospital and Peking University Shougang Hospital from January 1st 2000 to August 31st 2016 were collected. There were 18 radical prostatectomy (RP) cases and 10 transrectal prostatic biopsy cases. Contemporaneously, 445 elderly (>55 years) patients were collected, of which 385 had detailed pathological information, were chosen as control group. The mean age of young group was 51 years (29-55 years). Follow-up data for 22 cases were available (1-110 months). The correlation of the clinicopathological features and prognosis were analyzed retrospectively.@*Results@#Presurgical prostatic specific antigen (PSA) level was abnormal in young patients, with 18 cases (64.3%) had elevated fPSA level, 26 (92.9%) had increased tPSA level, and 26 (92.9%) had decreased fPSA/tPSA ratio. Gleason score (GS) was 8 in 10.7% (3/28) of cases, and 9 in 42.9% (12/28) of cases. Of the 18 patients with RP, 17 (94.4%) had pT stage ≥pT2c. PSA level (P=0.006) and GS (P=0.001) were positively correlated with pT stage. Family history of PCa in 1st degree relatives was found in 9.1% of the cases. During follow-up, 2 patients died of PCa, 7 patients showed progression within 24 months. There were no significant differences in PSA level and GS between young patients and elderly patients, while the former group was more likely to have incontinence (P=0.023), higher PSA levels (P=0.001), and lower overall survival (P=0.049). Only postsurgical PSA level was found to be negatively associated with overall survival (P=0.030) and cancer specific survival (P=0.021) in young patients.@*Conclusions@#Presurgical PSA level and GS are positively correlated with pT stage of early onset PCa. Compared with elderly patients, young patients are more likely to have incontinence, higher postsurgical PSA level, and lower overall survival. Among all the parameters, only postsurgical PSA level shows an adverse impact on prognosis of early onset PCa. Young patients, especially those with family history, may benefit from studies on the susceptibility loci and phenotype of PCa.
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Objective: To access the risk for smoking on morbidity of acute ST-segment elevation myocardial infarction (STEMI) at different gender and age population. Methods: A case-control study was conducted in 2026 STEMI patients and 2026 control subjects with matched gender and age (±2 years) in our hospital from 2010-01-14 to 2016-02-27. The relationship between smoking and STEMI morbidity was analyzed. Results: Smoking was an important risk factor for STEMI morbidity in male gender and it was negatively related to age, as STEMI in young male smokers (≤45 years): adjusted OR=7.000, 95% CI 4.235-11.570; in middle age male smokers (46-59 years):adjusted OR=5.296, 95% CI 3.904-7.185 and in elder male smokers (≥60 years): adjusted OR=4.686, 95% CI 2.860-4.751. Conclusion: Smoking is a major risk factor for STEMI morbidity, while it is different from age and gender; the young male smokers have the highest risk to suffer from STEMI.
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Objective To observe the effects of autophagy on the expression of synaptic plasticity related protein, growth-associated pro-tein-43 (GAP-43) and microtubule associated protein-2 (MAP-2), in CA1 area of hippocampus of vascular dementia rats. Methods Nine-ty-six healthy male Sprague-Dawley rats were randomly divided into sham group, vascular dementia model group (VD group), autophagy in-hibitor 3-methyl adenine preconditioning group (3-MA group) and autophagy agonist rapamycin preconditioning group (Rap group). Each group was divided randomly into subgroups of one week, two weeks, four weeks and eight weeks after modeling, six rats in each group. The vascular dementia rat model was established with modified Pulsineli's four-vessel occlusion. The expression of GAP-43 and MAP-2 in CA1 area of hippocampus were detected with immunohistochemistry. Results Compared with the sham group, the expression of GAP-43 protein increased, and the expression of MAP-2 protein decreased at every time point in VD group (P<0.01). Compared with VD group, the expres-sion of both GAP-43 and MAP-2 increased in 3-MA group (P<0.05), and decreased in Rap group (P<0.05). Conclusion Autophagy may in-hibit the expression of synaptic plasticity related protein, GAP-43 and MAP-2, in CA1 area of hippocampus in vascular dementia rats, indi-cating inhibition of autophagy may promote synaptic remodeling.
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Objective To investigate the association of the rs 2118181 polymorphism of FBN-1 gene ( encoding Fibrillin-1 ) and the risk of acute aortic syndrome ( AAS ) in Chinese Han population. Methods Genomic DNA was extracted from the blood of 206 patients suffering AAS and 209 individual-matched controls.The dideoxy chain termination method was used to determine the genotypes of rs 2118181 single nucleotide polymorphisms .Results The TT frequency of rs 2118181 genotype was significantly higher in the patients with AAS , especially with Intramural Haematoma ( IMH ) than in the controls ( 62.1%, 70.4% vs.52.5%, P<0.05).Carriers of CT or CC genotype had a less risk for AAS , especially for IMH, compared with carriers of TT genotype.The odds ratio were 0.66 (95%CI:0.45-0.98, P=0.040) and 0.46 (95%CI:0.24-0.87, P=0.016) respectively.After adjusting for age, sex, body mass index, hypertension , body mass index , smoking , diabetes mellitus , the odds ratio for AAS was 0.66 ( 95% CI:0.44-0.99 , P=0.048 ) .However , there was no significant difference on the frequencies of rs 2118181 genotype between the two subgroups of classical aortic dissection and intramural haematoma . Conclusions The rs2118181 polymorphism of FBN-1 gene is correlated to the sporadic AAS , especially to IMH, in Chinese Han population .The carriers of TT genotype are vulnerable to AAS , especially to IMH , compared with the non-carriers.
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Objective To observe the neural protection of 3-n-butylphthalide (NBP) injection in focal cerebral ischemia-reperfusion rats. Methods 160 male Sprague-Dawley rats were randomly divided into sham group (n=10), ischemia-reperfusion group (IR group, n=50), high-dose NBP treatment group (high-dose group, n=50), middle-dose NBP treatment group (middle-dose group, n=25) and low-dose NBP treatment group (low-dose group, n=25). The later 4 groups were occluded the middle cerebral artery for 2 hours and reperfused. The sham group was sacrificed 24 hours after operation, and the other groups at 6, 12, 24, 48 and 72 hours after reperfusion, in which 5 of them were stained with TdT mediated dUTP Nick End Labeling (TUNEL) to observe the neuronal apoptosis, and immunohistochemistry to observe the expression of silent information regulation 2 homolog 1 (SIRT1) and peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α);the other 5 of sham group, IR group and high-dose group were observed with quantitative real-time PCR of SIRT1 and PGC-1α. Results Compared with the IR group, the number of apoptotic cells decreased and the SIRT1 and PGC-1αpositive cells increased in all NBP groups at each time (F>160.60, P4.13, P<0.01). Conclusion NBP can protect brain from apoptosis in focal cerebral ischemia-reperfusion rats, which may relate to more ex-pression of SIRT1 and PGC-1α.
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Objective This study was aimed to evaluate the remote real-time transmission 12-lead electrocardiogram system on door-to-balloon time in patients with ST-segment elevation myocardial infarction.Methods We retrospectively analyzed the consecutive patients with STEM I who had accepted primary percutaneous coronary intervention (PCI) in the chest pain center of our hospital from February 2012 to July 2012.The study group consisted of patients with pre-hospital ECG,while the control group included patients without pre-hospital ECG,Their door-to-balloon time and door-to-catheter room time,mortality w ere compared.Results Totally 60 consecutive patients who had received primary PC I for STEMI were evaluated.Among them,35 patients were hospitalized with pre-hospital ECG while the other 25 patients without ECG.The Pre-hospital ECG was associated with a significautly shorter median door-to-balloon time (38 min vs.94min;P ＜0.01),The proportion of patients received balloon dilation within the guidelinerecommended 90 min timeframes Was significantly higher in pre-hospital ECG group than in non pre-hospital ECG group (94.6％ vs.60％;P =0.001).No difference was observed in mortality between the two groups (5.7％vs.4％;P ＞ 0.05),Significant difference was seen in the median hospital time in study group (5 compared with control group (7day) (5 day vs.7 day;P ＜ 0.01).Conclusions The remote real-time transmission 12-lead electrocardiogram system is associated with a significantly shorter door-to-balloon time in STEMI patients.The remote real-time transmission 12-lead electrocardiogram system is recommended in patients suspected STEMI.
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@#Objective To observe the effect of Yangxue Qingnao Granule on the ultrastructures and expression of p38 mitogen activated protein kinases (p38MAPK) in CA1 area of hippocampus in vascular dementia rats. Methods 180 Sprague-Dawley rats were randomly di-vided into sham group, vascular dementia model group (model group) and Yangxue Qingnao Granule treatment group (treatment group). The vascular dementia was modeled with modified Pulsineli's four-vessel occlusion. The ultrastructure of CA1 area was observed with trans-mission electron microscope, while the expression of p38MAPK in CA1 area was detected with immunohistochemstry and Western blotting 1, 2, 4 and 8 weeks after modeling. Results In the model group, pyknosis, nuclear dissolution, heterochromatin margination and mitochon-dria swelling were found in most of the neurons in CA1. In the treatment group, the distribution of chromatin was well-proportioned, and mi-tochondrion and other organelle were normal. In the model group, the expression of p38MAPK increased at each time point compared with the sham group (P<0.01), and peaked 4 weeks after modeling, and decreased in the treatment group compared with the model group (P<0.01). Conclusion Yangxue Qingnao Granule can improve the ultrastructure of neuronal in CA1 area of hippocampus of vascular dementia rats, which may relate with the inhibition of the expression of p38MAPK.
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Objective To observe the changes of ischemic preconditioning on the expression of hypoxia inducible fac?tor (HIF)-1αand vascular endothelial growth factor (VEGF) in ischemia hippocampus CA1 region after focal cerebral isch?emia/reperfusion (I/R) in rats, and the mechanisms of brain protection from brain ischemia preconditioning (BIP) thereof. Methods The male SD rats were randomly divided into three groups:sham operation (SO) group,middle cerebral artery oc?clusion (MCAO) group and brain ischemia preconditioning (BIP) group. The MCAO group and BIP group were further divid?ed into six subgroups according to perfusion time after I/R including 2 h, 6 h, 12 h, 24 h, 48 h and 72 h. The ischemia pre?conditioning model rats were established. Immunohistochemistry and Western blot assay were used to observe the expres?sions of HIF-1αand VEGF in ischemia hippocampal CA1 region. Results Neurological function deficit was not observed in SO group. Compared with MCAO group, there was a lower neurological function deficit score in BIP group. In MCAO group and BIP group, the expressions of HIF-1αand VEGF positive cells and protein increased at 2 h after I/R, then gradu?ally increased from 6 h to12 h and reached the maximum level at 24 h, then gradually decreased. The levels were still higher at 72 h than those of SO group. The number of HIF-1αand VEGF positive cells and protein were significantly increased in MCAO group and BIP group than that of SO group (P<0.05). The number of HIF-1αpositive cells was higher in BIP group than that in MCAO group except 2 h and 6 h reperfusion groups. The expression of VEGF positive cells, HIF-1αand VEGF protein were significantly higher in BIP group than those in MCAO group at different time points (P < 0.05). Conclusion Ischemic preconditioning plays a protective role in brain, which may be related to up-regulation of HIF-1αand VEGF.