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Vaccinations are widely credited with reducing death rates from COVID-19 but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2. At autopsy, immunostaining of COVID-19 lungs showed highly elevated expression of GRP78 in both pneumocytes and macrophages compared to non-COVID control lungs. GRP78 expression was detected in both SARS-CoV-2 infected and un-infected pneumocytes as determined by multiplexed immunostaining for nucleocapsid protein. In macrophages, immunohistochemical staining for GRP78 from deceased COVID-19 patients was increased but overlapped with GRP78 expression taken from surgical resections of non-COVID-19 controls. In contrast, the robust in situ GRP78 immunostaining of pneumocytes from COVID-19 autopsies exhibited no overlap and was independent of age, race/ethnicity and gender compared with non-COVID-19 controls. Our findings bring new insights for stress-response pathways involving the proteostatic network implicated for host resilience and suggest that targeting of GRP78 expression might afford an alternative therapeutic strategy to modulate host-viral interactions during SARS-CoV-2 infections.
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Objectiveezrin gene is overexpressed in pancreatic cancer, and its upstream sequence plays an important role in gene expression. This study intends to knock out ezrin transcriptional regulatory region and identify its gRNA target sites for gene editing in pancreatic cancer cells.MethodsThe reporter gene expression vectors carrying the upstream segment of ezrin gene were transiently transfected into Panc-1 cells. The ezrin transcriptional regulatory regions were identified by double luciferase reporter gene detection system. Then, the online software was utilized to predict the gRNA target sites located at the upstream and downstream of ezrin transcriptional regulatory region. Two recombinant plasmids pX459-sgRNA-L and pX458-sgRNA-R contained these two sequences were constructed for gene editing. Moreover, in order to identify the targeted knockout of ezrin transcriptional regulatory region, the recombinant plasmids were co-transfected into Panc-1 cells, and the genome DNA contained gRNA target sites were amplified, subcloned and sequenced. Finally, Panc-1 cells transfected with recombinant plasmids were preliminary sorted using puromycin treatment. The cell proliferation was detected by water-soluble tetrazolium salt method.ResultsLuciferase data showed that ezrin gene fragment -1297/-1186 enhanced the transcriptional activity of SV40 promoter and ezrin promoter in Panc-1 cells. Subclonal sequencing data revealed that the recombinant plasmids carrying the gRNA target sequence of ezrin transcriptional regulatory region were co-transfected into Panc-1 cells could trigger the genomic DNA fragments, which located between gRNA-L and gRNA-R target sites. Cell proliferation assay showed that the proliferation was significantly inhibited after transfection.ConclusionThe targeted knockout of ezrin transcriptional regulatory region was achieved and the inhibition of Panc-1 cell proliferation may be related to this knockout.
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Objective: To study the possible mechanism of dichroa alkali salt (DAS) in inducing vomiting. Method: Mice pica model was used to observe the antagonistic effect of the three different kinds of antiemetic drugs[dopamine receptor antagonist metoclopramide, 5-hydroxytryptamine 3 (5-HT3) receptor antagonist ondansetron and neurokinin-1 receptor antagonist aprepitant] on body mass, food intake, kaolin consumption, diarrhea and death induced by DAS to preliminarily clarify the possible pathogenic pathway of DAS. Then, the expression of 5-HT and substance P(SP) in ileum and medulla of mice induced by DAS alone at different time points was detected by enzyme-linked immunosorbent assay to confirm whether DAS could affect the changes of these two neurotransmitters. Result: After treatment with ondansetron and aprepitant, DAS-induced reduction in food intake of mice was significantly improved on the 4th day after continuous administration and on the 1st day after drug administration (Prd day after administration, DAS-induced body mass loss of mice was significantly improved (PConclusion: The mice pica model can be used to effectively characterize DAS-induced vomiting. DAS-induced pica in mice may be associated with the increase of 5-HT and SP in ileum and medulla. Ondansetron and aprepitant can effectively antagonize DAS-induced pica in mice.
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<p><b>OBJECTIVE</b>Aging is associated with a progressive decline in muscle strength, muscle mass and impaired physical function, which reduces mobility and impairs quality of life in the elderly population. The 6-12 months of exercise can enhance the muscle strength, but these improvements can only be maintained for a short period. In this study, we investigated the effects of long-term Tai Chi (TC) exercise on muscle strength of lower extremities.</p><p><b>METHODS</b>A cross-sectional study was conducted in 205 long-term TC practitioners (age: 60-89 years) and 205 age and gentle matched controls who did not practice TC. Each of the activity group was further divided into three distinct age groups: G1, 60-69 years; G2, 70-79 years; and G3, 80-89 years. Hand-held dynamometery was used to measure the maximum isometric strength of iliopsoas, quadriceps femoris, tibialis anterior and hamstrings in both sides of the participants. Unpaired t tests were performed to compare the difference of strength between the TC and non-Tai Chi (NTC) groups. Multivariate analysis of variance (MANOVA) was used to compare the lower muscle strengths among the different age groups in the TC and NTC groups. Pearson's correlations were used to quantify the linear relationship between the months of TC practice and lower limbs muscle strength.</p><p><b>RESULTS</b>The inter-rater reliabilities of iliopsoas, quadriceps femoris, tibialis anterior and hamstrings were intraclass correlation coeffificient (ICC) (1,1) = 0.895 (0.862-0.920), ICC (2,2) = 0.905 (0.874-0.928), ICC (3,3) = 0.922 (0.898-0.941) and ICC (4,4) = 0.930 (0.908-0.947). The strength of the muscles in the TC group did not differ among different age groups (P>0.05). The strength of iliopsoas, quadriceps femoris, tibialis anterior and hamstrings in TC group was higher than that in the NTC group (P<0.05). A correlation between muscle strength and extension of the exercise period was positive (P<0.05).</p><p><b>CONCLUSIONS</b>Results shed light on the orientation and magnitude of long-term TC in preventing muscle strength loss with aging. TC might be a good form to slow down the trend of age-related decline in muscle strength in community-dwelling population.</p>
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Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Envelhecimento , Fisiologia , Extremidade Inferior , Fisiologia , Força Muscular , Fisiologia , Reprodutibilidade dos Testes , Tai Chi ChuanRESUMO
<p><b>BACKGROUND</b>High levels of nitric oxide (NO) produced by inducible NO synthase (iNOS) have been associated with atherosclerosis processes. Naoxintong is a traditional Chinese medicine for treatment of cerebrovascular and cardiovascular disease. The aim of the present study was to detect and quantify changes of iNOS mRNA and NO levels in the vessel wall after the administration of Naoxintong in an atherosclerotic rabbit model.</p><p><b>METHODS</b>Forty New Zealand white rabbits were randomly divided into five groups (n = 8). Rabbits were fed a standard diet (group A), an atherogenic diet consisting of 79% standard feed + 1% cholesterol + 5% lard + 15% egg yolk powder (group B), an atherogenic diet with Naoxintong 0.25 mg×kg(-1)×d(-1) (group C), an atherogenic diet with Naoxintong 0.5 mg×kg(-1)×d(-1) (group D), or atherogenic diet with Naoxintong 1.0 mg×kg(-1)×d(-1) (group E) for 12 weeks.</p><p><b>RESULTS</b>Supplemented administration of Naoxintong led to a down-regulation of cholesterol (CHOL) (P < 0.001) and low-density lipoprotein (LDL) (P < 0.001). The trend became more notable as the dose of Naoxintong increased; group C vs. group B (CHOL, P = 0.568; LDL-cholesterol (LDL-C), P = 0.119), group D vs. group B (CHOL, P = 0.264; LDL-C, P = 0.027), group E vs. group B (CHOL, P = 0.028; LDL-C, P = 0.002). Atherosclerotic lesions in aorta were reduced in Naoxintong groups (groups C, D, E) compared to group B. Group B had higher iNOS mRNA (P = 0.001) and NO level (P < 0.001) than group A. Compared with the atherogenic diet fed-rabbits, Naoxintong supplements decreased the expression of iNOS mRNA (P < 0.001) and the NO level (P < 0.001) in the vessel wall. Groups given a higher Naoxintong dose exhibited greater benefits. iNOS mRNA and NO levels seemed to be reduced in group C, although the difference did not quite reach statistical significance (iNOS mRNA, P = 0.130; NO, P = 0.038). iNOS mRNA and NO levels significantly decreased in group D (iNOS mRNA, P = 0.019; NO, P = 0.018) and group E (iNOS mRNA, P = 0.004; NO, P < 0.001).</p><p><b>CONCLUSION</b>Naoxintong has beneficial effects on atherosclerosis treatment by reducing expression of iNOS mRNA and the NO level in the vessel wall.</p>
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Animais , Coelhos , Aterosclerose , Tratamento Farmacológico , Metabolismo , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Óxido Nítrico , Metabolismo , Óxido Nítrico Sintase Tipo II , Genética , MetabolismoRESUMO
<p><b>BACKGROUND</b>Our previous study had demonstrated that ulinastatin (UTI) had a neuroprotective effect in experimental autoimmune encephalomyelitis (EAE). Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE.</p><p><b>METHODS</b>Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/ myelin basic protein (MBP)/ the precursor form of nerve growth factor (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting.</p><p><b>RESULTS</b>The combined treatment group had a lower clinical score (0.61 ± 0.06) and demyelinating score (1.33 ± 0.33) than the groups with normal saline (clinical score: 1.39 ± 0.08, P < 0.001; demyelinating score: 2.75 ± 0.49, P < 0.05) or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP (1.14 ± 0.06 vs. 0.65 ± 0.04, P < 0.001), MBP (1.28 ± 0.14 vs. 0.44 ± 0.17, P < 0.001), and decreased expressions of proNGF (1.08 ± 0.10 vs. 2.32 ± 0.12, P < 0.001), p75 (1.13 ± 0.13 vs. 2.33 ± 0.17, P < 0.001), and iNOS (1.05 ± 0.31 vs. 2.17 ± 0.13, P < 0.001) proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP (1.28 ± 0.14 vs. 1.01 ± 0.15, P < 0.05) expression and downregulate iNOS (1.05 ± 0.31 vs. 1.35 ± 0.14, P < 0.05) expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment (1.08 ± 0.10) than that in UTI (1.51 ± 0.24, P < 0.05) or methylprednisolone (1.31 ± 0.04, P < 0.05) treatment group.</p><p><b>CONCLUSION</b>Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.</p>
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Animais , Feminino , Camundongos , Combinação de Medicamentos , Encefalomielite Autoimune Experimental , Tratamento Farmacológico , Glicoproteínas , Usos Terapêuticos , Metilprednisolona , Usos Terapêuticos , Camundongos Endogâmicos C57BL , Esclerose Múltipla , Tratamento FarmacológicoRESUMO
<p><b>OBJECTIVE</b>To study the association between the clustering manifestation of factors as overweight and central obesity, family heredity, immoderate alcohol drinking, tobacco smoking, hyperlipidemia, hyperglycemia and the prevalence of hypertension.</p><p><b>METHODS</b>Data was from a program related to the comprehensive prevention and control strategies on cardiac-cerebral vascular disease carried out in the communities of Shanghai, to describe the relationship between the clustering of risk factors and hypertension. This program included 15 158 people with complete data at the age of 35 - 74, from 2008 - 2011. Both single factor and multi-factor analysis were used and longitudinal study was performed to further explore the causal relationship.</p><p><b>RESULTS</b>The overall prevalence of hypertension at the baseline survey was 41.9%. The associated ORs (age-adjusted) of hypertension parallelly increased with the number of risk factors under clustering. The associated OR of the males with 1, 2, 3, 4 as well as 5 and above risk factors were 3.157 [95% confidence interval (CI): 2.152 - 4.630], 6.428 (95%CI: 4.435 - 9.319), 11.797 (95%CI: 8.135 - 17.105), 19.723 (95%CI: 13.414 - 29.000), 33.051 (95%CI: 21.449 - 50.930) respectively. In females with 1, 2, 3 as well as 4 risk factors, the associated ORs were 2.917 (95%CI: 2.374 - 3.585), 6.499 (95%CI: 5.307 - 7.959), 15.717 (95%CI: 12.609 - 19.591) and 31.719 (95%CI: 21.744 - 46.270), respectively. For longitudinal study, the 2-year incidence of hypertension in males and females were 1.9% and 1.6%, respectively. Compared to those people without risk factors, the incidence was higher in the people with a larger number of clustering. When the clustering number reaching 2 or 3 in females, the relative risk (RR) were 2.111 (95%CI: 1.024 - 4.350) and 3.000 (95%CI: 1.287 - 6.995) respectively, with statistically significant difference.</p><p><b>CONCLUSION</b>The risk of hypertension parallelly increased with the clustering number of relevant risk factors. Comprehensive prevention and control on related risk factors was required.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Viés , China , Epidemiologia , Hipertensão , Epidemiologia , Estudos Longitudinais , Prevalência , Características de Residência , Fatores de RiscoRESUMO
<p><b>BACKGROUND</b>Despite the large scale technical innovations that have been made, a number of patients with neuromyelitis optica (NMO) are lacking NMO-IgG in both serum and cerebrospinal fluid. Longitudinally extensive spinal cord (LESC) lesions and linear lesions are associated with NMO. However, differences of spinal cord magnetic resonance imaging (MRI) features, including LESC lesions and linear lesions, between NMO-IgG positive and negative patients still remain unknown. The aim of the present study was to analyze the relationship between NMO-IgG status and spinal cord MRI features in NMO patients, particularly concerned about LESC lesions and linear lesions.</p><p><b>METHODS</b>Clinical data and spinal cord MRI of 52 NMO patients were retrospectively analyzed. Eight patients were NMO-IgG negative in both serum and cerebrospinal fluid, while 44 were NMO-IgG positive. Quantitative data between the two cohorts were compared by the Student's t test or Mann-Whitney U test, the chi-square test or Fisher's exact test was used to evaluate qualitative data.</p><p><b>RESULTS</b>NMO-IgG negative patients had a higher sex ratio (male/female) (P = 0.014). On axial MRI, lesions in the NMO-IgG negative group were mostly located in the peripheral cord (50%), and central lesions (55%) were more common in the NMO-IgG positive group (P = 0.051). LESC lesions were common in both cohorts. None of linear lesions was found in NMO-IgG negative patients, while the NMO-IgG positive cohort had significantly more linear lesions (48%) (P = 0.016).</p><p><b>CONCLUSIONS</b>Patients with NMO-IgG negativity may have different spinal cord lesion features compared to NMO-IgG positive patients. Diagnosis of NMO cannot be excluded even when NMO-IgG negativity and non-specific spinal lesions occur.</p>
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Imunoglobulina G , Sangue , Líquido Cefalorraquidiano , Imageamento por Ressonância Magnética , Neuromielite Óptica , Sangue , Líquido Cefalorraquidiano , Patologia , Estudos Retrospectivos , Medula Espinal , PatologiaRESUMO
<p><b>OBJECTIVE</b>To study the anatomical and biomechanical features of sacral pedicle and lateral mass so as to provide reference for clinical screw fixation technology of sacral pedicle and lateral mass.</p><p><b>METHODS</b>A total of 60 adult patients'spiral CT images of the sacrum and coccyx were selected randomly. The entry points of sacral pedicle and lateral mass screws were determined, and the screw trajectory was measured using the three dimensional reconstruction method. Meanwhile, the gross anatomy was scrutinized in 15 adult cadaver specimens to determine the sacral pedicle and lateral mass screw entry points. The length, width and angle of sacral pedicle and lateral mass screw trajectory were measured. Eight of 15 cadaver specimens were selected to test the maximal extraction force of sacral pedicle and lateral mass screws. The clinical data of 15 cases treated by pedicle and lateral mass screw technology were collected and analyzed.</p><p><b>RESULTS</b>The diameter and length of S(1)-S(5) sacral pedicle and lateral mass screw trajectory were regular, with about 20 degree inclination angle. The S(1) pedicle screw entry point was located at the intersection point of the basal lateral part of articular process and median line of transverse process, and no significant difference was found for the maximal extraction force between pedicle and lateral mass screws (P larger than 0.05). The entry points of S(2)-S(5) pedicle screws were located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of the transverse process. The lateral mass screw entry point of S(2)-S(5) was on the median side of intersection point between median line of the transverse process and lateral sacral crest. The maximal extraction force of pedicle screws was significantly greater than that of lateral mass screws (P less than 0.05).</p><p><b>CONCLUSION</b>Both the sacral pedicle and the lateral mass screw fixation techniques can offer effective fixation and reconstruction for fracture of the sacrum and coccyx, but pedicle screw fixation may be more convenient, safe and reliable than lateral mass screw fixation.</p>
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Adulto , Feminino , Humanos , Masculino , Fenômenos Biomecânicos , Parafusos Ósseos , Fixação Interna de Fraturas , Métodos , Imageamento Tridimensional , Sacro , Fisiologia , Cirurgia Geral , Tomografia Computadorizada por Raios XRESUMO
Objective To study the anatomical and biomechanical features of sacral pedicle and lateral mass to provide evidence for clinical sacral pedicle and lateral mass screw fixation technology. Method 60 adult patient's spiral CT images of sacrum and coccyx were selected randomly. The sacral pedicle and lateral mass screw entry point was determined, and the crew trajectory were measured using the three dimensional reconstruction. Meanwhile, the gross anatomy was done for 15 adult cadavers to determine the sacral pedicle and lateral mass screw entry point. The length, width and angle of sacral pedicle and lateral mass screw trajectory was measured. 8 of 15 cadaver specimens were selected to test for the maximal extraction force for sacral pedicle and lateral mass screws. ResultsThe diameter and length of S1~S5 sacral pedicle and lateral mass screw trajectory are significantly regular, with inclination angle is about 20°. The S1 pedicle screw entry point is located at intersection point of basal lateral part of articular process and median line of transverse process, no significant difference is found between the maximal extraction force of pedicle and lateral mass screws (P>0.05). The entry points of S2~5 pedicle screws are located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of transverse process. The lateral mass screw entry point of S2~5 is on the median side of intersection point between median line of transverse process and lateral sacral crest. The maximal extraction force of pedicle screws are significantly different from the lateral mass screws(P<0.05). Conclusions Both the sacral pedicle and the lateral mass screw fixation technology can offer effective fixation and reconstruction for the fracture of sacrum and coccyx, but the pedicle screw fixation may be more convenient, safe and reliable than the lateral mass screw fixation technology.
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Objective To elucidate the expression of gankyrin in human gastric cancer cells and it's role in nimesulide induced apoptosis. Methods Four human gastric cancer cell lines including MKN28 (well differentiated), AGS (poorly differentiated), MKN45 (poorly differentiated), and SGC7901(moderately differentiated) were cultured and treated with nimesulide. Nimesulide induced growth inhibition and apoptosis of the cells were detected by methyl thiazolyl tetrazolium assay, and confirmed by flow cytometry. The expressions of gankyrin gene and protein were further assessed by real-time PCR and Western blotting. Results Gankyrin mRNA and protein were detected in all four human gastric cancer cell lines. The proliferations of AGS and SGC7901 cell lines were significantly suppressed by nimesulide in a time-dose dependent manner. When treated with 400 μmol/L of nimesulide for 48 hours, the significant apoptosis was found in AGS cells (23.30%±2.50%) and SGC7901 cells (16.80%±1.55% ) in comparison with controls (0.57%±0.19% and 0.88%± 0.17%, respectively, all P values <0.01). Apoptosis of AGS cells induced by nimesulide was accompanied by a considerably decreased gankyrin expression that was more significant at 24 hours (0.0035±0.0014) and 36 hours (0.0980±0.0160) in comparison with controls (0.4690±0.1190, all P values<0.01). Conclusion Gankyrin expresses in human gastric cancer cell lines and may be involved in nimesulide induced apoptosis of AGS cells.
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<p><b>OBJECTIVE</b>to evaluate the risk factors for postoperative pulmonary complications following transoral operation for the atlanta-axis disorders.</p><p><b>METHODS</b>total 104 cases were collected from January 2005 to June 2009. Twelve variables among patients with PPCs and without PPCs were analyzed by logistic regression analysis.</p><p><b>RESULTS</b>the incidence of postoperative pulmonary complications following transoral operation for the atlanta-axis disorders was 22.1% (23/104). There was significantly difference in 9 variables between patients with PPCs and without PPCs, and 5 variables as serum albumin < 35 g/L (OR = 15.185, P = 0.003), tracheotomy (OR = 32.254, P = 0.015), Frankle grade (OR = 8.866, P = 0.001), the duration of intubation > 4 d (OR = 7.934, P = 0.002), the duration of surgery > 6 h (OR = 16.889, P = 0.006) were found to be significantly related to the development to postoperative pulmonary complications by multivariate analysis.</p><p><b>CONCLUSION</b>serum albumin < 35 g/L, tracheotomy, Frankle grade, the duration of intubation > 4 d, the duration of surgery > 6 h are the risk factors for postoperative pulmonary complications following transoral operation for the atlanta-axis disorders.</p>
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Vértebra Cervical Áxis , Cirurgia Geral , Atlas Cervical , Cirurgia Geral , Modelos Logísticos , Pneumopatias , Boca , Cirurgia Geral , Análise Multivariada , Complicações Pós-Operatórias , Fatores de RiscoRESUMO
Objective To explore the correlation of tumor growth and endothelial progenitor cells (EPC) entering blood induced by surgical injury in tumor bearing nude mice. Methods Forty-two tumor bearing nude mice were randomly divided into seven groups (n=6): non-surgical injury groups (1 d and 30 d), anesthetic group, surgical injury groups (24 h, 48 h, 72 h and 30 d after surgery). Blood samples and xenograft tumor tissues were taken from anesthetic group 24 h after anaesthesia and surgical injury groups 24 h, 48 h, 72 h and 30 d after surgery. EPC levels in peripheral blood were measured by flow cytometry, serum VEGF levels were determined by ELISA, microvessel density (MVD) and expression of VEGF were detected by immunohistochemistry. Results The levels of EPC in 24 h post-surgery group, 48 h post-surgery group and 72 h post-surgery group were significantly higher than that in non-surgical injury 1 d group (P<0.05). The levels of VEGF in 24 h post-surgery group, 48 h post-surgery group, 72 h post-surgery group and anesthetic group were significantly higher than that in non-surgical injury 1 d group (P<0.05). There was no significant difference in MVD among groups (P>0.05). Pearson correlation analysis revealed that serum VEGF levels were related to EPC levels in peripheral blood (r=0.695 6, P<0.01), while EPC levels in peripheral blood were not related to MVD (r=0.221 4, P>0.05), and serum VEGF levels had no correlation with MVD (r=0.224 9, P>0.05). Conclusion Surgical injury has no obvious influence on xenograft tumor growth.
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Objective To investigate the inhibitory effect of X-linked inhibitor of apoptosis associated factor-1(XAF1) on xenograft growth in nude mice with hepatocellular carcinoma. Methods The models of xenografted nude mice with human hepatocellular carcinoma cell line SMMC7721 were established. Intratumor injection was performed on three tumor sites in each group of mice (n=5) with recombinant adenovirus Ad5/F35-XAF1, control virus Ad5/F35-Null at the same infective titre or PBS of the same volume every two days for two weeks. The volumes of xenografts in all nude mice were measured every three days, and the differences between Ad5/F35-XAF1 group and the other two groups were compared. The apoptosis of tumor cells was determined by in situ end-labeling TUNEL method, the expression of XAF1 protein and microvessel density (MVD) were detected by immunohistochemistry. Results Intratumoral injection of Ad5/F35-XAF1 significantly inhibited the growth of tumor xenografts with smaller tumor size, less tumor weight and lower MVD compared with those injected with control virus Ad5/F35-Null and PBS (P<0.05 or P<0.01). However, the apoptosis index and expression of XAF1 protein in Ad5/F35-XAF1 group were significantly increased compared with the other two groups (P<0.01). Conclusion Ad5/F35-XAF1 significantly inhibits xenograft growth in nude mice with hepatocellular carcinoma, which is probably associated with the effects of XAF1 inducing hepatocellular carcinoma cell apoptosis and suppressing tumor angiogenesis.
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Objective To evaluate changes of regional cerebral metabolism by proton MR spectroscopy (~1H-MRS) in patients with minimal hepatic encephalopathy (MHE) and to correlate these changes with the neuropsychological test. Methods Fifty-four patients with cirrhosis including nine patients with hepatic encephalopathy (HE),23 patients with MHE,22 patients without HE and 13 controls underwent neuropsychological tests and ~1H-MRS scanning. The volumes of interest included occipital gray matter and left parietal white matter regions. Ratio of spectral peak areas of N-acetylaspartate (NAA),choline (Cho),myo-inositol (mI),and glutamine/glutamate (Glx) relative to creatine (Cr) were acquired. Statistical analysis was conducted using independent t test and one-way analysis of variance. The results of different groups were compared by using the nonparametric Mann-Whitney U test with Bonferroni correction. Correlations among the ~1H-MRS ratios, the grade of HE, neuropsychological test and ammonia data were calculated with Spearman correlation test. Results The ratios of NAA/Cr,Cho/Cr,mI/Cr,Glx/Cr of the occipital gray matter and left parietal white matter regions in patients with cirrhosis are 1.55±0.12,0.48±0.10,0.42±0.14,2.52±0.48 and 1.73±0.17,0.75±0.16,0.42±0.16,2.75±0.59respectively,and they are 1.53±0.10,0.48±0.09,0.51±0.11,2.20±0.39 and 1.69±0.15,0.82±0.14,0.53±0.12,2.40±0.40 in patients without HE,1.58±0.13,0.48±0.08,0.38±0.13,2.62±0.39 and 1.78±0.18,0.74±0.14,0.38±0.15,2.84±0.58 in patients with MHE,1.54±0.12,0.50±0.13,0.29±0.07,3.04±0.31 and 1.70±0.19,0.62±0.16,0.29±0.07,3.37±0.38 inpatients with HE.Compared with controls, decreased mI/Cr and Cho/Cr ratios and elevated Glx/Cr ratios were found in patients with cirrhosis (t=3.196,9.394,-6.527,P<0.01,occipital gray matter. t=5.592,9.717,-6.681,P<0.01,left parietal white matter= and in subgroup of patients without HE, with MHE and HE (F=5.097,25.896,20.204,P<0.01,occipital gray matter.F=16.435,28.660,21.283,P<0.01,left parietal white matter).Significant difference in these metabolic alterations was also found among the different groups of cirrhosis especially the ratios of Glx/Cr in occipital gray matter and left parietal white matter (P<0.0084).The ratios of mI/Cr also significantly altered between patients without HE and with MHE (P<0.0084).There was a significant negative correlation between the ratios of Cho/Cr,mI/Cr and the grade of HE (P<0.01= and a significant positive correlation between the ratios of Glx/Cr and the grade of HE (r=0.709,P<0.01,occipital gray matter; r=0.720,P<0.01,left parietal white matter=.NCT-A and DST of controls is (49±8) s and 39±6.They are (134±37),(83±26),(64±22) second and 15±2,25±9,35±8 in patients with HE,MHE and without HE respectively.The metabolic alterations of Cho/Cr,mI/Cr,Glx/Cr correlated significantly with neurepsychological tests in all subjects (P<0.01=.There was a significant positive and a negative correlation between the ratios of Glx/Cr and the data of NCT-A and DST respectively (r=0.570,-0.642,occipital gray matter; r=0.541,-0.632,left parietal white matter).The metabolic alterations of Glx/Cr had no correlation with ammonia data as well as other metabolic alterations.Conclusions ~1H-MRS study shows cerebral metabolic alterations of gray and white matter in patients with cirrhosis,especially the reduction in mI/Cr ratio and increase in Glx/Cr ratio. These changes correlate well with the neuropsychological tests and may be useful in predicting the presence of MHE.
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Objective To elucidate the effect of clavulanic acid (CLA) in suppressing the antibiotic resistance of Helicobacter pylori (Hp) to metronidazole (MZ) and its mechanism. Methods All Hp strains were isolated from biopsy specimens taken endoscopically and random amplified polymorphic DNA assay (RAPD) was used to certificate the distinct origin of these strains. The minimum inhibitory concentration (MIC) of CLA and MZ aganst Hp were determined by using agar dilution procedure and Epailometer test (E-test). The effect of CLA on the morphology of Hp was examined by transmission electron microscopy. Fluorescein-C6-aminopenicillanic acid (FLU-C6-APA) competition assay was used to detect the binding between CLA and penicillin-binding proteins (PBPs). Results Eleven strains were isolated. In vitro CLA could decrease the MIC of MZ resistant(1.442±0.459 vs 0.376±0.288, P=0.0077), but not affect the MIC for MZ sensitive strains significantly (P>0.05). Exposure to CLA resulted in morphological changes of Hp, including cell wall disintegration and cell lysis. Furthermore, CLA inhibited the binding of FLU-C6-APA to PBPs(30.5-33.5×103). Conclusions CLA suppresses the antibiotic resistance of Hp to MZ through its binding with PBPs which results in the morphology changes of Hp.
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<p><b>OBJECTIVE</b>To study the cost of the hypertensive outpatients.</p><p><b>METHODS</b>The study randomly selected 460 insured patients with hypertension and investigated their cost on each case in the out-patient department through 2002, based on the electronic system of medical insurance.</p><p><b>RESULTS</b>As a whole, the distribution of hypertensive outpatient expenditure takes on the positively skewed, with the median of 1 567.9 Yuan RMB. With the increase of age, the average expenses in each age group increased accordingly. In the study, the average number of outpatient attendances per patient was 19.5, the average expenses per visit was 115.4 Yuan RMB. In age groups 40 - 49 and 50 - 59, expenses of outpatient in male and female groups are obviously different in 2002 (Wilcoxon W(40 - 49) = 36, P(40 - 49) = 0.037; Wilcoxon W(50 - 59) = 374, P(50 - 59) = 0.023), as well as the number of out-patients (Wilcoxon W(40 - 49) = 52.5, P(40 - 49) = 0.007; Wilcoxon W(50 - 59) = 379, P(50 - 59) = 0.028). When considering the factors of gender and age at one time, the outpatient expenditures in the male group were significantly different between the different age groups (chi(2) = 22.3, P < 0.001), as well as the number of outpatients (chi(2) = 25.4, P < 0.001). In addition, the expenditure of drugs, which took a large proportion of the total expenditure of hypertensive outpatients (about 83.6 percent), was divided into three parts according to the degree of correlation with hypertension: direct expenses related to the with disease, the indirect expenses and the irrespective. The proportions of each part were 19.9 percent, 32.3 percent and 47.8 percent respectively.</p><p><b>CONCLUSION</b>When economic evaluation of community prevention is carried out, the cost and cost-benefit analysis based on the analysis of outpatient expenditure and the proportion of expenses on hypertension should be taken into account. Additionally, to provide appropriate mode of medicare, to impact the behaviors and expenditure of patients, and to provide low-cost but good effective drug are also essential and important factors.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Etários , Assistência Ambulatorial , China , Custos de Cuidados de Saúde , Hospitais Comunitários , Economia , Hipertensão , Economia , Terapêutica , Pacientes Ambulatoriais , Fatores Sexuais , Fatores de TempoRESUMO
Objective To evaluate the precise,accurate and specific of two direct methods for measuring low-density lipoprotein cholesterol(LDL-C)based on the principle of selective hydrolysys. Methods Both DAIICHI and Randox reagents were compared with PVS method and the ultracentrifugally separated HDL and LDL fractions were used.Results Both methods all had good precise,the total CV was 3.96%~4.42%(Daiichi)and 0.78%~3.19%(Randox),repectively.The average concentrations of 48 serum samples were 3.68±1.23 mmol/L(PVS method),3.25±1.11 mmol/L(DAIICHI method)and 3.37±1.21 mmol/L(Randox method),respectively.There was no statistics difference between the results from PVS method and other two direct methods.Furthermore it indicated that the results determined by both direct methods had good relationship with that by PVS method.It also indicated that both direct methods had good specific to LDL-C.The dilute test demonstrated that there were good linearity between both direct methods of LDL-C and the linearity range was 9.28 mmol/L at least.Conclusion The direct methods for determining LDL-C based on the principle of selective hydrolysis possessed good precise and accurate and specific to LDL-C,and was meet with clinical application.
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Whether InfusaSleeve(IS) catheter can deliver antisense oligodeoxynucleotide (ODNs) following arterial denuation is unknown. We evaluate the feasibility of local endoluminal delivery of C-myc ODNs to the site of arterial denudation by using IS catheter and to determine the biological importance of these effects. IS catheter was introduced into right side of iliac artery of 21 rabbits after angioplasty of iliac artery. Animals were randomized to the control group (n=6) receiving saline injection and the treated group receiving c-myc antisense (n=15, 1 mg ODNs per vessel). In two weeks and 40 days following the operation, angiography was performed. Morphometric analyses were carried out in balloon-denuded iliac arteries. The expression of c-myc protein was detected by using a mouse monoclonal antibody to c-myc. Morphometric analyses carried out at 40 days after transcatheter c-myc antisense oligomer administration. The results showed that maximal neointimal area was reduced from 7.66±3.7(×105 μm2) in the control group (n=6) to 4.04±1.02(×105 μm2) in the antisense treated group (n=6, P<0.05). These changes in vascular remodeling following denuding injury resulted in an increase in residual luman from 20~50% in the control group to 70~90% in the antisense-treated group. C-myc protein expression was virtually undetectable at baseline in locally ODNs-delivered arteries and detectable in control denuded arteries. The results show that: ①Single IS transcatheter administration allowed endoluminal delivery of ODNs to the site of arterial injury; ② c-myc antisense oligomer reduced the formation of neointime in denuded arteries, implying a therapeutic potential of this approach.
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Objective To evaluate X-ray stereotactic localized biopsy with resident metal wire in the diagnosis of breast minutelesions. Methods 28 cases of breast minute lesions were analyzed retrospectively,all cases were non-palpable clinically,but were positive by mammography.Needle biopsies were executed under X-ray stereotactic localization,and a thin metal wire was sited in lesion to instruct resection. Results All of 28 cases with minute lesion were successfully localized and completely resected,localization satisfaction rate was 93% percent.Pathological diagnosis showed benign lesion in 19 cases,and malignant lesion in 9 cases.Among the 9 malignant cases,there were 5 cases of invasive duct carcinoma,1 case of duct carcinoma with early invasion,2 cases of duct carcinoma,and 1 case of medullary carcinoma. Conclusion X-ray stereotactic localized biopsy with resident metal wire can provide accurate localization and precise diagnosis,especially in the diagnosis of occult breast cancer.It is an efficient method in the diagnosis of early breast carcinoma.