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BACKGROUND@#Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.@*METHODS@#We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.@*RESULTS@#The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.@*CONCLUSION@#Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
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Aged , Female , Humans , Male , Middle Aged , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Arteries , Atrophy , Brain/metabolism , Cerebral Cortex/metabolism , Cerebrovascular Circulation , Constriction, Pathologic/pathology , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methodsABSTRACT
Objective:To investigate the diagnostic value of 11C-Pittsburgh compound B (PIB) in patients with mild cognitive impairment (MCI) and Alzheimer′s disease (AD) and explore the factors that may affect the binding of 11C-PIB. Methods:From January 2017 to December 2019, the 11C-PIB uptake of 6 patients with normal cognitive (NC; 3 males, 3 females, age: (64.5±12.3) years), 11 patients with MCI (4 males, 7 females, age: (64.5±9.8) years) and 21 patients with AD (7 males, 14 females, age: (68.1±9.1) years) from Daping Hospital, Army Medical University were retrospectively analyzed. Regional 11C-PIB binding was assessed by using standardized uptake value ratio (SUVR) and visual reading of 11C-PIB scan. Clinical data, including age, gender, education level, cognitive impairment, neuropsychological scale score, vascular risk factors (VRF), apolipoprotein E (ApoE) gene, were collected and differences among groups were analyzed by using one-way analysis of variance, least significant difference t test or Fisher exact test. Factors that affected the 11C-PIB binding were analyzed by multiple linear regression. Results:SUVR of cerebral lobe among NC, MCI and AD groups were significantly different (range of mean SUVR: 1.16-1.26, 1.19-1.35 and 1.40-1.61; F values: 5.331-9.279, all P<0.05). For positive PIB patients, SUVR of posterior cingulate and precuneus were increased in MCI group compared with NC group (1.20±0.15 vs 1.50±0.12, 1.18±0.15 vs 1.59±0.13; F values: 6.389 and 10.668, t values: -2.33 and -3.10, both P<0.05), and there were no significant differences in all lobes between MCI and AD group ( t values: from -1.29 to -0.51, all P>0.05). Visual analysis showed that the positive rates of PIB in frontal lobe (85.7%(18/21)), posterior cingulate (85.7%(18/21)), precuneus (81.0%(17/21)), temporal lobe (81.0%(17/21)) and occipital lobe (47.6%(10/21)) in AD were higher than those in MCI (4/11, 4/11, 4/11, 3/11 and 1/11, respectively; all P<0.05). Multiple linear regression showed that the degree of cognitive impairment were independent risk factors for SUVR of all lobes ( b values: 0.377-0.536, all P<0.05). The ApoE ε4 gene was independent risk factor for SUVR of precuneus ( b=0.290, P<0.05). Conclusion:11C-PIB is helpful for clinical diagnosis of MCI and AD patients and the degree of cognitive impairment and ApoE ε4 gene may be independent risk factors for increasing 11C-PIB binding.
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Objective:To retrospectively analyze the prevalence and genotype distribution of human papillomavirus (HPV) among women in mainland China from the introduction of cervical cancer vaccine to its marketing in China, so as to provide data for comparing HPV prevalence after the application and gradual promotion of HPV vaccine.Methods:Related articles published during 2006 to 2016 were retrieved from PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang databases. Data about HPV infection in women receiving physical examination or routine cervical cancer screening and female outpatients were collected and analyzed.Result:A total of 270 articles were retrieved, in which the sampled women were aged from 13 to 90 years old. Seventy-two articles were about HPV infection in women screened for cervical cancer with a sample size of 580 308 people. The overall results showed that during the 11 years, the five most common high-risk HPV genotypes were HPV52, 16, 58, 68 and 18, and the common low-risk HPV genotypes were HPV81, 43 and 6. The distribution of HPV genotypes varied in different regions, but HPV16, 52 and 58 were always the predominant genotypes. Among the 270 collected articles, 200 analyzed HPV infection in female outpatients with a total of 675 035 cases. The results showed that the top five high-risk HPV genotypes with high prevalence were HPV16, 52, 58, 18 and 33, and the common low-risk types were HPV6, 11 and 81. The analysis of HPV infection rate in seven geographical regions indicated that, although the distribution of the commonly circulating high-risk HPV genotypes varied in different regions, HPV16, 52 and 58 remained the predominant genotypes.Conclusions:The present study showed that the prevalence and genotype distribution of HPV infection varied by region, but HPV16, 52 and 58 were always the most common high-risk genotypes and HPV6 was the predominant low-risk genotype in both women screened for cervical cancer and female outpatients. Besides that, the infections of other high-risk genotypes, such as HPV53 and 68, should also be of concern.
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Norovirus is one of the leading causes of acute non-bacterial gastroenteritis. Emergence of new genotypes due to frequent genetic recombination and antigenic drift increases the prevalence of noro-virus infection worldwide. Norovirus infection has become a global public health concern. This review fo-cused on disease burden, vaccine research, cell culture and animal models regarding norovirus infection.
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Objective@#To detect norovirus (NoV) GⅠ.1- and GⅡ.4-specific IgG, IgA and histo-blood group antigen (HBGA)-blocking antibodies in healthy populations of all age groups in China for better understanding the epidemiological features of norovirus in China from a serological point of view and providing basic data for vaccine development and clinical trial design.@*Methods@#Indirect ELISA and HBGA-blocking assay were used to detect NoV-specific IgG, IgA and HBGA-blocking antibodies in serum samples collected from healthy natural populations (n=839, aged from six months to 88 years old) in Guangzhou, Fuyang and Yantai. The results were statistically analyzed.@*Results@#The total positive rates of NoV GⅠ.1- and GⅡ.4-specific IgG antibodies were 91.9% and 93.0%. The positive rates of GⅠ.1- and GⅡ.4-specific IgA antibodies were 48.6% and 75.6%, and the titers of HBGA-blocking antibodies to GⅠ.1 and GⅡ.4 norovirus were 5.04 (95%CI: 4.63-5.49) and 18.15 (95%CI: 16.11-20.44). The positive rates of IgG and IgA antibodies generally showed an increasing trend with age. The positive rates of GⅠ.1- and GⅡ.4-specific IgG antibodies ranged from 79.2% to 100.0% and 76.7% to 100.0% in different age groups. They were 81.7% and 85.0% in the age group of 0.5-<1 year, 79.2% and 76.7% in the age group of 1-<2 years, and 98.1% and 96.3% in the age group of 12-<18 years, and maintained at 96% and 98% in the older age groups. The positive rates of GⅠ.1-specific IgA antibody ranged from 11.7% to 93.8% in different age groups and rapidly increased with age. It was 11.7% in the age group of 0.5-<1 year, and reached 93.3% in people aged 45-<60 years and 93.8% in people aged ≥60 years. The positive rates of GⅡ.4-specific IgA antibody ranged from 50.8% to 88.8% in different age groups with 50.8% in people aged 0.5-<1 year, and 86.7%-90.7% in people aged 12-<18 years and older. The titer of GⅠ.1 HBGA-blocking antibody generally increased with age. The antibody titer in populations aged 0.5-<12 years old was lower than that in those aged 18 years and above (GMT: 2.98-4.07 vs 8.21-11.62, P<0.001), and the titer in people of 12-<18 years old was lower than that in those of 45 years old and above (GMT: 5.21 vs 11.03-11.62, P<0.05). No obvious change with age was observed in the titer of GⅡ.4 HBGA-blocking antibody excepting the significant difference between populations of 2-<5 and 22-<45 years old (GMT: 26.73 vs 11.87, P<0.01).@*Conclusions@#This study revealed the characteristics of serum NoV GⅠ.1- and GⅡ.4-specific IgG, IgA and HBGA blocking antibodies in populations of different age groups in central and eastern China through analyzing their positive rates and titers and provided preliminary seroepidemiological data for the development of NoV vaccines in China.
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Objective To make a preliminary assessment on the immunogenicity of a quadriva-lence recombinant human papillomavirus (HPV) vaccine (6, 11, 16 and 18 types) (Hansenulapolymor-pha) in healthy women aged 18-45 years in phaseⅠclinical study. Methods It was a single-center, doub-le-blind, randomized, placebo-controlled phaseⅠclinical study. Women aged 18-45 years were randomized (2 : 1) to receive HPV vaccine (n=60) or placebo control (n=30) at months 0, 2 and 6. Antibodies against HPV6/11/16/18 were detected by pseudovirus-based neutralisation assay in serum samples collected at 0 d, 180 d and 210 d. Seroconversion rates and geometric mean titres ( GMT) of antibodies against the four types of antigens were calculated. Results Seroconversion rates of the vaccination group at 180 d ( be-fore the third dose) and 210 d ( one month after the third dose) were generally similar and between 85％-100％ for all types of antibodies. The GMT of antibodies at one month after the last dose improved signifi-cantly compared with those before immunization. Conclusions These results showed that the HPV vaccine had good immunogenicity in the population of healthy women aged 18-45 years. Higher antibody titers were elicited by the vaccine compare with the tites before the first dose and in the placebo control group.
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Objective@#To make a preliminary assessment on the immunogenicity of a quadrivalence recombinant human papillomavirus (HPV) vaccine (6, 11, 16 and 18 types) (Hansenulapolymorpha) in healthy women aged 18-45 years in phaseⅠclinical study.@*Methods@#It was a single-center, double-blind, randomized, placebo-controlled phaseⅠ clinical study. Women aged 18-45 years were randomized (2∶1) to receive HPV vaccine (n=60) or placebo control (n=30) at months 0, 2 and 6. Antibodies against HPV6/11/16/18 were detected by pseudovirus-based neutralisation assay in serum samples collected at 0 d, 180 d and 210 d. Seroconversion rates and geometric mean titres (GMT) of antibodies against the four types of antigens were calculated.@*Results@#Seroconversion rates of the vaccination group at 180 d (before the third dose) and 210 d (one month after the third dose) were generally similar and between 85%-100% for all types of antibodies. The GMT of antibodies at one month after the last dose improved significantly compared with those before immunization.@*Conclusions@#These results showed that the HPV vaccine had good immunogenicity in the population of healthy women aged 18-45 years. Higher antibody titers were elicited by the vaccine compare with the tites before the first dose and in the placebo control group.
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Human norovirus (NoV) is the major cause of human acute non-bacterial gastroenteritis worldwide. The development of NoV vaccines is limited by the inability to culture cells in vitro and the lack of small animal models. Thus, traditional methods used to prepare live attenuated vaccines are not suitable for preparing NoV vaccines. Subunit vaccines against NoV infection, especially virus-like particle (VLP)-based vaccines, have outstanding advantages in the research and development of NoV vaccines. In this review, we focused on reviewing recent advances in the fields of NoV VLP-based vaccines and the development of NoV VLP-based vaccines using different expression systems as well as identifying the research direction for NoV VLP-based vaccines.
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Objective To evaluate the immune effects of virus-like particles ( VLPs) assembled from the capsid protein VP1 of a recombinant norovirus ( NoV) GⅡ. 17 genotype. Methods The recombi-nant NoV GⅡ. 17 VP1 VLPs were purified, and then tested by SDS-PAGE and Western blot to analyze the purity. The size, morphology and diameter distribution of the recombinant VLPs were detected by transmis-sion electron microscopy ( TEM) and dynamic light scattering ( DLS) analyzer. The recombinant VP1 VLPs adsorbed by aluminium adjuvant were used to immunize BALB/c mice. Serum samples were collected after immunization. Specific antibody level and neutralizing antibody activity were evaluated with enzyme linked immunosorbent assay ( ELISA) and histo-blood group antigen ( HBGA)-VLP blocking test. Cross-reactivity of serum samples with GⅠ. 1 and GⅡ. 4 VP1 VLPs were detected. Moreover, cross-protection against GⅠ. 1 and GⅡ. 4 VP1 VLPs was analyzed. Results The purity of the recombinant NoV GⅡ. 17 VP1 VLP was greater than 90％ and specific bands were detected by Western blot. TEM images and DLS experiments showed that VLPs were 30-50 nm in size with good morphology and uniformity, indicating that the recombi-nant VLPs were similar to the wildtype virus. High titers of specific antibodies were detected in serum sam-ples of the immunized mice. A certain degree of cross-reactions between serum samples and VP1 VLPs of NoV GⅠ. 1 and GⅡ. 4 were observed, but no cross-protection was detected. Conclusion The recombinant GⅡ. 17 VP1 VLPs in combination with aluminum adjuvant can induce higher titers of HBGA blocking anti-bodies in mice, suggesting that it could be used as a candidate target antigen for norovirus vaccine.
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Objective To review and investigate the malaria control history of Wuzhou City,Guangxi Zhuang Autonomous Region from 1950 to 2015,so as to provide the evidence for future malaria control and surveillance. Methods The data of ma?laria control in Wuzhou City from 1950 to 2015 were collected and analyzed. Results In 1950 decade,the malaria incidence in Wuzhou City was 1 435.55/100 000,higher than the average level in Guangxi,and the mortality of malaria was 0.95/100 000. The malaria incidence of local residents was reduced to 3.61/100 000 in 1979 and no local malaria case was found since. The im?ported malaria cases were found in Wuzhou City since 1980,and were more than local cases since 1981. In recent five years, 87.50%(7/8)of imported malaria cases were from south?east Asia. Conclusions Wuzhou City has reached the national criteri?on of malaria elimination,but the imported malaria is the recent threat. The surveillance and control work of malaria should be strengthened.
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Objective To investigate the physicochemical properties and immunogenicity of virus like particles(VLPs) in two different conformations assembled from the essential capsid protein VP1 of GⅡ.4 norovirus(NoV) in Hansenula polymorpha. Methods NoV GⅡ.4 VLPs in two different conforma-tions were prepared from high-density fermentation of recombinant engineered strains and VLPs purification. Physicochemical properties of the two forms of VLPs were identified by Western blot,size-exclusion high per-formance liquid chromatography (SEC-HPLC), dynamic light scattering(DLS) and transmission electron microscopy. Serum VLPs binding activities and blocking activities against VLPs binding to histo-blood group antigen(HBGA-VLPs) were evaluated after immunization of BALB/c mice with the two forms of VLPs. Re-sults VLPs of two different diameters with high homogeneity were obtained after purification. DLS results showed that particle sizes of two VLPs were 53.98 nm and 45.18 nm,respectively. The two VLPs were sim-ilar in binding abilities to HBGA receptors. Serum VLPs binding activities and blocking activities against HBGA-VLPs were found higher in NoV-VLP-L than NoV-VLP-S,but the difference was not statistically sig-nificant (P>0.05). Conclusion VLPs in two different conformations were obtained by expressing NoV GⅡ.4 VP1 proteins in Hansenula polymorpha. Though they were similar in physicochemical properties and immunogenicity,the NoV-VLP-L might be potential antigen candidates for the development of recombinant human norovirus vaccine.
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BACKGROUND: In animal experiments, ultrasound-mediated microbubbles can promote the homing of transplanted stem cells to the ischemic area, enhance angiogenesis and small arterial formation, improve local blood flow in the ischemic myocardium and restore myocardial contractility.OBJECTIVE: To investigate the effect of ultrasound-mediated microbubbles on intravenously transplanted bone marrow mesenchymal stem cell (BMSC) homing and the therapeutic efficiency on ischemic stroke. METHODS: A middle cerebral artery occlusion (MCAO) model was induced by plug wire preparation. At 72 hours after MCAO, model rats were randomized into four groups: PBS group (n=15), BMSCs group (n=18), ultrasound+BMSCs group (n=18), ultrasound+microbubble+BMSCs group (n=18). Corresponding treatment was done in each group: 2 mL of PBS was injected via tail vein in the PBS group; about 3×106 BMSCs diluted by 2 mL of PBS were injected via tail vein slowly in the BMSCs group; after skull ultrasound radiation (1 MHz, 2 W/cm2) for 120 seconds, BMSCs were injected via tail vein slowly in the ultrasound+BMSCs group; the same process as the ultrasound+BMSCs group was done following intravenous injection of 0.1 mL/kg microbubbles in the ultrasound+microbubble+BMSCs group.RESULTS AND CONCLUSION: (1) Forty-eight hours after BMSCs transplantation, the BMSCs homing rate in the brain was significantly higher in the ultrasound+microbubble+BMSCs group than the other two groups (P < 0.05). (2) Twenty-eight days after MCAO, nerve damage was significantly milder in the ultrasound+microbubble+BMSCs group than the other two groups (P < 0.05). (3) Seven days after transplantation, the water content in the brain tissue was significantly lower in the ultrasound+microbubble+BMSCs group than the other two groups (P < 0.05). (4) Seven days after transplantation, the cerebral infarction volume was significantly reduced in the ultrasound+microbubble+BMSCs group compared with the other two groups (P < 0.05). To conclude, ultrasound-mediated microbubbles can enhance the homing effect of intravenously transplanted BMSCs, reduce cerebral edema and cerebral infarction volume, improve the neurological function, and increase the therapeutic effect of BMSCs transplantation on ischemic stroke.
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Objective: To compare the effects of MRI- and CT-guided interventional therapies on uterine fibroids
Methods:A total of 280 patients with uterine fibroids who were treated in our hospital from August 2008 to February 2014 were selected and divided into a treatment group and a control group by random draw [n=140]. The control group and the treatment group were subjected to CT- and MRI-guided interventional therapies for uterine artery embolization
Results:After three months of treatment, 94.3% and 92.9% of heavy menstrual bleeding and pelvic pressure of the treatment group were relieved respectively, which were similar to those of the control group [92.9% and 92.1% respectively] [P>0.05]. The two groups had similar uterine and fibroid sizes before treatment, which were all significantly decreased after treatment [P<0.05] when the treatment group had significantly smaller uteri and fibroids than the control group did [P<0.05]. The serum follicle-stimulating hormone, luteinizing hormone, estradiol levels, arterial resistive indices and endometrial thicknesses of the two groups were similar before treatment, which were significantly increased after treatment [P<0.05]. Meanwhile, the values of the two groups became significantly different [P<0.05]. The treatment group was also significantly less prone to complications such as fever, vaginal bleeding and hematuria than the control group after treatment [P<0.05]
Conclusion:Interventional therapy, especially that guided by MRI, can be performed accurately and safely by mildly affecting the ovary and by promoting the recovery of uterine artery blood flow and endometrial thickness
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Objective To evaluate the immune effects of virus-like particles ( VLPs) of VP1 pro-teins derived from norovirus GⅠ. 1 and GⅡ. 4 genotypes expressed in Hansenula polymorpha expression sys-tem. Methods SDS-PAGE and Western blot assay were performed to detect the purity of GⅠ. 1 and GⅡ. 4 VP1 proteins after purification. Morphologies of the recombinant VLPs were observed under transmission electron microscopy ( TEM) . Sizes and distributions of the VLPs were analyzed by dynamic light scattering analyzer. BT50(50% of blocking titer) was detected by HBGA (histo-blood group antigen) blocking assay in BALB/c mice immunized with different regimens. Results SDS-PAGE analysis of the purified recombinant GⅠ. 1 and GⅡ. 4 VP1 proteins showed that their purity were greater than 90%. Western blot assay con-firmed the specific bands of VLPs. TEM images showed that the sizes of purified GⅠ. 1 and GⅡ. 4 VP1 VLPs were at a mean diameter of 30-50 nm with clear border and high homogeneity, which was similar to that of wild virus. BT50 significantly increased in the groups, in which Al( OH) 3 was used as adjuvant. Con-clusion Animal studies have shown that administration of GⅠ. 1 and GⅡ. 4 VP1 VLPs in the presence of Al( OH) 3 induces detectable HBGA-blocking antibody, indicating that GⅠ. 1 and GⅡ. 4 VP1 VLPs are promising candidates for norovirus vaccine.
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Objective To evaluate the effect of aescine sodium combined with albumin in the treatment of hypertensive intracerebral hemorrhage after intracranial hematoma minimally invasive removal surgery.Methods 50 patients with hypertensive intracerebral hemorrhage after intracranial hematoma minimally invasive removal surgery were randomly divided into the two groups:the treatment group was treated with aescine sodium and albumin,the control group was treated with the conventional medical drugs;The neural function defect scale,brain edema area of postoperative patients after 1d and 15d,clinical effects after 15d were observed.Results 15d after operation,in the treatment group,the brain edema area was (2.40 ± 0.32) cm2,neural function defect scale was (9.44 ± 2.25) points,which were better than (3.40 ±0.85) cm2 (t =4.721,P ＜0.01) and (15.65 ±3.04) points(t =3.625,P ＜0.01).The total effective rate of the treatment group was 88.9％,which was better than 69.6％ of the control group(x2 =13.58,P ＜0.01).Conclusion Aescine sodium combined with albumin can effectively reduce perihematomal brain edema area,improve nerve function defect and clinical effect in the patients with hypertensive cerebral hemorrhage after minimally invasive scavenging surgery.
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Objective Toinvestigatetheclinicalsignificanceofplasmamatrixmetalloproteinase9 (MMP-9)intheformationofdelayedcerebraledemaafterintracerebralhemorrhage.Methods The clinical data of 107 patients with spontaneous intracerebral hemorrhage treated with conservative medical treatment were analyzed retrospectively. According to the clinical features and imaging changes,they were divided into either a delayed cerebral edema group (case group n=39)or a non-delayed cerebral edema group (control group n =68 ). The plasma MMP-9 level was detected with enzyme-linked immunosorbent assay within 24 h after onset. The patients performed head CT scan again at day 7 and 14 after admission. The changes of hematoma and edema volume were detected. All the possible factors associated with the formation of delayed cerebral edema were firstly analyzed by the univariate analysis. Univariate analysis showed that the variables with significant differences were enrolled into multiple logistic regression analysis. Results TheplasmaMMP-9levelofthedelayedbrainedemagroupwassignificantlyhigherthanthatof the control group,they were 189 ± 51 and 118 ± 27 mg/L respectively (P<0. 01). The result of univariate analysis showed that age,history of smoking,blood glucose level,baseline hematoma volume,and National Institute of Health stroke scale (NIHSS )score on admission might be associated with the formation of delayed cerebral edema after intracerebral hemorrhage. Logistic regression analysis showed that MMP-9 level (OR,9. 745,95%CI 6. 754-15. 466,P<0. 01),baseline hematoma volume (OR,2. 411,95%CI 1. 190-2. 728,P =0. 018),blood glucose level on admission (OR,1. 327,95%CI 1. 133 -1. 850,P =0.004),and NIHSS score (OR,1. 867,95%CI 1. 272-2. 364,P=0. 020)were the independent risk factorsfortheformationofdelayedcerebraledemaafterintracerebralhemorrhage.Conclusion Theamount of bleeding,NIHSS score,and hyperglycemia are the risk factors for the formation of delayed cerebral edema in patients with spontaneous intracerebral hemorrhage,while high MMP-9 level on admission indicated that the risk of the formation of delayed cerebral edema is high.
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Objective To investigate the effects on brain tissue p38 mitogen-activated protein kinase (MAPK) and aquaporin 4 (AQP4) and neuroprotective effect of edarvone after focal cerebral ischemia and reperfusion in mice.Methods A total of 196 healthy male Kunming mice were randomly divided into four groups:a sham operation group,an ischemia-reperfusion group,a saline control group,and an edaravone group (n =49 in each group).A middle cerebral artery occlusion (MCAO) mothod was used to induce a cerebral ischemia-reperfusion model.At 2 h after ischemia,immediately after reperfusion in the edaravone group and the saline control group,edaravone (5 mg/kg) and the same volume of saline were injected intraperitoneally in mice,then repeated once every 24 h.At 2 h after MCAO,the brain water content and infarct volume at different time points after reperfusion (12 h,24 h,48 h,and 3 d) were measured respectively.At 24 h after MCAO,the expressions of AQP4 and p38 MAPK in the brain tissue of ischemic peripheral cortex were measured by Western blotting.Results The volumes of cerebral infarction (all P ＜ 0.01) and the brain water contents (all P ＜0.05) in the edaravone group were decreased than those in the ischemia-reperfusion group and saline control group at different time points,and they were most significant at 48 h.After 24-h reperfusion,the expression levels of AQP4 (0.985 ± 0.129,1.024 ± 0.117,0.713 ± 0.231) and phospho-p38 MAPK (1.123 ± 0.142,1.214 ± 0.096,0.986 ± 0.087) in the brain tissue of ischemic peripheral cortex in the ischemia-reperfusion group,the saline control group,and the edaravone group were upregulated significantly than those in the sham operation group (AQP4:0.265 ± 0.123;phospho-p38 MAPK:0.465 ±0.023;all P ＜0.01),but edaravone group were significantly lower than the ischemia-reperfusion group and the saline control group (all P ＜ 0.05).Conclusions Edaravone can downregulate the expression level of AQP4 and effectively protect cerebral ischemia reperfusion injury in mice,Its mechanism may be associated with the inhibition of p38 MAPK pathway.
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Objective To evaluate the immunogenicity of the recombinant human papillomavirus type 68b (HPV68b) virus-like particles(VLPs)in a mouse model.Methods The L1 protein of HPV type 68b was successful expressed in the Hansenula polymorpha strain (NVSI-68b-1).Processes including purifi-cation and reconstitution were performed to achieve pure HPV 68b VLPs.The purity, morphology and immu-nogenicity of the purified HPV 68 b VLPs were further analyzed .The BALB/c mice were immunized with HPV68b VLPs formulated on aluminum adjuvant .Pseudovirus-neutralizing antibody ( PsV NAb) assay was performed to detect the neutralizing antibodies in serum samples .Results The HPV 68 b L1 VLPs were ob-tained as indicated by the results of SDS-PAGE, Western blot assay , HPLC, electron microscopy and dy-namic light scattering with a high purity of 95%.Transmission electron microscopy and dynamic light scat-tering analysis revealed that the HPV68b L1 VLPs resembled the native virus with an average particle diame-ter of 50 nm.High levels of HPV68b-neutralizing antibodies were detected in serum samples from the mice immunized with HPV68b L1 VLPs.Moreover, a cross-protective efficacy of HPV68b L1 VLPs for HPV68a was observed .Conclusion This study suggested that the recombinant HPV 68 b VLPs expressed in a Han-senula polymorpha strain might be used as a potential candidate for the development of HPV vaccine .
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Objective To assess the safety of early subcutaneous injection of a low-dose low molecular weight heparin (LMWH) nadroparin for prevention of deep vein thrombosis (DVT) in patients with spontaneous intracerebral hemorrhage (sICH).Methods The patients with sICH who early using nadroparin or lower limb intermittent pneumatic compression (IPC) for prevention of DVT were enrolled.A nadroparin group continuously injected nadroparin 0.4 ml/d subcutaneously for 10 days at day 4 after admission and an IPC group used lower limb IPC.Head CT was reexamined and hematoma volume changes were evaluated at day 3,5,and 14 after admission.The hemorrhagic events during the course of treatment were documented,and the lower limb DVT was examined by color Doppler sonography.Results A total of 94 patients with acute sICH (n =41 in the nadroparin group,n =53 in the IPC group) who early use of nadroparin or IPC for prevention of DVT were enrolled.Fourteen patients had lower limb DVT,5 (12.2％) of them were in the nadroparin group and 9 (17.0％) of them were in the IPC group.However,there was no significant difference in the incidence of DVT between the two groups (x2 =0.418; P =0.518).During the treatment,no patient experienced increased intracranial hematoma and rebleeding.Conclusion Early subcutaneous injection of low-dose nadroparin for the prevention of DVT in patients with sICH is safe.
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Objective To analyze the genotype distribution of human papillomavirus( HPV) strains and their epidemiological characteristics in cervixes of Chinese females. Methods Pertinent litera-tures published during 2004 to 2013 were screened from PubMed,China National Knowledge Infrastructure (CNKI)and Wanfang database for data analysis. Results There were 245 studies screened out for the me-ta-analysis. A total of 661 658 cases met the inclusion criteria,ranging from 16 to 87 years old. All prov-inces and territories of China were covered by the data. The overall rate of HPV infection in cervix was 25. 0% among Chinese females. The predominant high risk genotype of human papillomavirus strains was HPV16,followed by HPV52,HPV58,HPV18,HPV33 and HPV31. HPV52 and HPV58 genotypes were more prevalent than HPV18 genotype. HPV35 and HPV45 genotypes were less popular. Conclusion The study suggested that the HPV infection showed obvious regional differences in genotypes. The genotype dis-tribution of HPV infection in China was different from that in other regions of the world. There were differ-ences with genotype distribution of HPV strains among seven geographic regions of China.