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Objective In this study, inbred BALB/c mice infected with the pneumonia virus of mice (PVM) were used to establish an animal model of viral pneumonia, and the changes in the pro-inflammatory alarmin molecule, high mobility group box 1 protein (HMGB1), during PVM infection were observed, as well as the in vivo intervention effects of the HMGB1 inhibitor, glycyrrhizic acid (GA), on PVM-induced lung injury. Methods Three-week-old female BALB/c mice were randomly divided into three groups, each consisting of 6 mice. One group, uninfected by PVM, served as the control group (Control). The other two groups were inoculated intranasally with PVM at a dose of 1×104 50% tissue culture infective dose (TCID50)/25 μL, and subsequently treated with GA saline solution (GA group) or plain saline solution (normal saline, NS group) via gavage for 15 consecutive days. During this period, changes in body weight and appearance were monitored in each group. At the end of the experiment, lung tissue samples were collected from all groups. The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry. The expression levels of HMGB1 and its Toll-like receptor 4 (TLR-4), advanced glycosylation end-product-specific receptor (AGER), and inflammatory cytokines such as interleukin (IL)-1β, IL-2, and tumor necrosis factor-α (TNF-α) in lung tissues of mice were measured using real time fluorescence quantitative PCR. Results Compared with the Control group, the NS group showed a significant weight loss after 6 days (P<0.05). Histopathological tests revealed pronounced inflammatory lesions in their lungs. Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm, and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1, IL-1β, and IL-2 were significantly upregulated (P<0.05). In the GA group, there was no significant change in the clinical symptoms or body weight. However, compared with the NS group, the pathological damages of lung tissues in the GA group were significantly reduced, and the expression levels of HMGB1, IL-1β, IL-2, and interferon-γ (IFN-γ) in lung tissues were also significantly decreased (P<0.05), although the expression level of AGER was significantly increased (P<0.05).ConclusionPVM infection can cause significant inflammatory pathological lung damages in mice, and GA can effectively alleviate the damages. Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.
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ObjectiveTo provide more basic information of comparative medicine for the study of biological changes and pathogenesis of COVID-19 by systematical sorting and analyzing the transcriptome data.MethodsFollowing a retrieval strategy, using COVID-19 and SARS-CoV-2 as key words, transcriptome datasets related to COVID-19 from January 2020 to May 2023 were collected from GEO, ArrayExpress and GEN Transcriptome databases. The composition, distribution, and research application of COVID-19 transcriptome data resources were analyzed. Data distribution was visually displayed and correlation analysis was performed. The research applications and limitations of existing COVID-19 transcriptome data were analyzed from the perspectives of clinical medicine and comparative medicine, focusing on clinical-related molecular mechanisms, biomarkers and related immune responses, treatment intervention strategies, etc. The research value and application prospects were discussed.Results A total of 975 sets of COVID-19 transcriptome data were included. Among three databases, datasets from humans accounted for the highest proportion, namely 71.9%, 77.9%, and 90%, respectively. Species other than humans, such as mice, were the main sources of data, with the respiratory and nervous systems having the highest distribution of data. Twenty-seven datasets were associated with clinical significance. Analysis revealed that respiratory tract injury and other related molecular mechanisms were obtained through transcriptome data mining. Biomarkers such as cfDNA could be used as therapeutic targets. The severity of COVID-19 infection was associated with cell changes and disorders represented by M1 macrophages. Comparative medical analysis showed that mice, hamsters, and other animals were susceptible to SARS-CoV-2. Rhesus monkeys and cynomolgus monkeys exhibited infection characteristics highly similar to human. Apart from respiratory symptoms, hamsters also exhibited digestive system symptoms. SARS-CoV-2 can replicate in the respiratory organs of various susceptible animals, the intestines of ferrets and the ears of minks, resulting in interstitial pneumonia, diffuse lung injury and other pathological changes of varying degrees. Based on the differences in immune responses, hamsters can be used for neutralizing antibody reaction research.Conclusion Currently there is a wealth of COVID-19 transcriptome data, but there is a lack of comparative transcriptome research. Transcriptomics can be combined with comparative medicine to further explore the differences in comparative medicine of COVID-19.
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Objective:To explore the differential diagnosis value of preoperative D-dimer in renal oncocytoma (RO) and chromophobe renal cell carcinoma (Ch-RCC) .Methods:From January 2015 to April 2022 in the Second Hospital of Anhui Medical University, clinical data of 47 cases of rare renal tumors were collected. According to postoperative pathology, patients were divided into RO group (15 cases) and Ch-RCC group (32 cases). General clinical data and preoperative blood indicators were analyzed. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were performed to evaluate the differential diagnosis value of D-dimer between RO and Ch-RCC.Results:There were no significant differences between two groups in gender ( χ2=0.41, P=0.522), age ( t=0.50, P=0.618), hypertension ( χ2<0.01, P=0.994), diabetes ( P=0.541), smoking history ( χ2=1.67, P=0.196), tumor laterality ( χ2=0.67, P=0.414). Besides, preoperative D-dimer was significantly higher in the Ch-RCC group [0.47 (0.29, 0.77) μg/ml] in comparison with RO group [0.21 (0.19, 0.27) μg/ml], with a statistically significant difference ( Z=4.44, P<0.001). In addition, there were no significant differences in hemoglobin ( t=-1.61, P=0.116), platelet ( t=0.26, P=0.800), leucocyte ( t=0.10, P=0.921), neutrophil ( t=-0.87, P=0.390), lymphocyte ( Z=0.82, P=0.418), monocyte ( Z=1.43, P=0.153), neutrophil-lymphocyte ratio ( Z=0.09, P=0.927), platelet-lymphocyte ratio ( t=0.42, P=0.676), and lymphocyte-monocyte ratio ( Z=-0.96, P=0.338) between Ch-RCC group and RO group. ROC curve analysis showed that when the cut-off value of preoperative D-dimer was 0.78 μg/ml, the AUC for differential diagnosis of RO and Ch-RCC was 0.90 (95% CI: 0.82-0.99, P<0.001), with a sensitivity of 0.78 and a specificity of 1.00. Conclusion:Preoperative level of D-dimer is significantly increased in Ch-RCC patients, which exhibits favourable preoperative differential diagnosis value between Ch-RCC and RO.
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This study aims to investigate the effect and mechanism of arctigenin(ARC) in the treatment of vascular endothelial injury in rats with pregnancy-induced hypertension(PIH). Fifty SD rats pregnant for 12 days were randomly assigned into a control group, a model group, an ARC group, a rapamycin(RAP, autophagy inducer) group, and an ARC+3-methyladenine(3-MA, autophagy inhibitor) group, with 10 rats in each group. The rats in the other groups except the control group were intraperitoneally injected with nitrosyl-L-arginine methyl ester(50 mg·kg~(-1)·d~(-1)) to establish the PIH model on the 13th day of pregnancy. On the 15th day of pregnancy, the rats in ARC, RAP, and ARC+3-MA groups were intraperitoneally injected with ARC(50 mg·kg~(-1)·d~(-1)), RAP(1 mg·kg~(-1)·d~(-1)), and 3-MA(15 mg·kg~(-1)·d~(-1))+ARC(50 mg·kg~(-1)·d~(-1)), respectively. The pregnant rats in the control group and the model group were intraperitoneally injected with the same amount of normal saline. The blood pressure and 24 h urine protein(24 h-UP) of pregnant rats in each group were measured before and after intervention. Cesarean section was performed to terminate pregnancy on day 21, and the body weight and body length of fetal rats were compared among groups. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes of placenta. The expression of endothelin-1(ET-1) and endothelial nitric oxide synthase(eNOS) in placenta was detected by immunohistochemistry. The serum levels of ET-1 and nitric oxide(NO) were determined with corresponding kits. The expression of microtubule-associated protein 1 light chain 3(LC3), Beclin-1, NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein with CARD domain(ASC), caspase-1, interleukin(IL)-1β, and IL-18 was determined by immunofluorescence and Western blot. The level of reactive oxygen species(ROS) in placenta was measured by fluorescence staining. The results showed that on day 12 of pregnancy, the blood pressure and 24 h-UP had no significant differences among groups. On days 15, 19, and 21, the blood pressure and 24 h-UP in the model group were higher than those in the control group(P<0.05). On days 19 and 21, the blood pressure and 24 h-UP in ARC group and RAP group were lower than those in the model group(P<0.05), and they were higher in the ARC+3-MA group than in the ARC group(P<0.05). On day 21, the model group had lower body weight and body length of fetal rats(P<0.05), higher serum level of ET-1, and lower serum level of NO(P<0.05) than the control group. Moreover, the placental tissue showed typical pathological damage, down-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and eNOS(P<0.05), up-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1β, and IL-18(P<0.05), and elevated ROS level. Compared with the model group, ARC and RAP groups showed increased body weight and body length of fetal rats(P<0.05), lowered serum level of ET-1, elevated serum level of NO(P<0.05), reduced pathological damage of placental tissue, up-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and eNOS(P<0.05), down-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1β, and IL-18(P<0.05), and lowered ROS level. Compared with ARC group, 3-MA reversed the effects of ARC on the above indicators. In conclusion, ARC can inhibit the activation of NLRP3 inflammasome and mitigate vascular endothelial damage in PIH rats by inducing autophagy of vascular endothelial cells.
الموضوعات
Female , Pregnancy , Animals , Rats , Humans , Rats, Sprague-Dawley , Hypertension, Pregnancy-Induced/drug therapy , Endothelial Cells , Inflammasomes , Interleukin-18 , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Beclin-1 , Cesarean Section , Reactive Oxygen Species , Placenta , Caspase 1 , Autophagyالملخص
Objective:To investigate the correlation between uncoupling protein 2 (UCP2) and fat mass and obesity associated (FTO) gene polymorphisms and visceral fat area in a population undergoing health examinations.Methods:In this retrospective cohort study, 120 people who underwent physical examination in the Health Management Department of Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from January 2020 to December 2021 with a visceral fat area ≥100 cm 2 under the abdominal navel section CT images were included in the superstandard group. In addition, 120 people who received health checkup in the meantime with a visceral fat area <100 cm 2 were included in the normal group. Basic information including age, gender, height, weight, body mass index (BMI), and visceral fat area was collected for both groups. Genotyping was performed, and logistic regression analysis was used to determine the association between UCP2 and FTO gene polymorphisms and visceral fat area. Results:The weight, body mass index, total cholesterol, triglyceride and low density lipoprotein cholesterol (LDL-C) in the superstandard group were all significantly higher than those in the normal group [(78.74±5.35) vs (65.83±4.22) kg, (27.89±3.24) vs (23.43±2.91) kg/m 2, (3.21±1.51) vs (2.32±1.47) mmol/L, (5.29±1.34) vs (4.86±1.16) mmol/L, (2.73±0.89) vs (2.51±0.82) mmol/L], the level of high density lipoprotein cholesterol (HDL-C) was significantly lower than that in normal group [(1.02±0.31) vs (1.23±0.43) mmol/L] (all P<0.05); there were no significant differences in age, gender, height, fasting blood glucose and glycated hemoglobin between the two groups (all P>0.05). The expression ratio of AG/GG allele in UCP2-866A/G and TA, AA and A allele in FTO rs9939609 gene locus in superstandard group were all significantly higher than those in normal group (82.50% vs 69.17%, 38.33% vs 19.17%, 7.50% vs 4.17%, 23.75% vs 15.00%) (all P<0.05). The expression of UCP2 gene ( OR=2.303, 95% CI: 1.456-3.642) and FTO gene ( OR=2.782, 95% CI: 1.149-6.733) were positively correlated with increased visceral fat area (both P<0.05). Conclusion:The presence of UCP2-866A/G or FTO rs9939609 gene polymorphisms in individuals undergoing health examinations significantly increases the risk of increased visceral fat area.
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BACKGROUND@#Asymptomatic coronary artery stenosis (ACAS) ≥50% is common in patients with acute ischemic cerebrovascular disease (AICVD), which portends a poor cardiovascular and cerebrovascular prognosis. Identifying ACAS ≥50% early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients. This study aimed to investigate whether aortic arch plaque (AAP), an early atherosclerotic manifestation of brain blood-supplying arteries, could be a predictor for ACAS ≥50% in AICVD.@*METHODS@#In this cross-sectional study, atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography (CTA) in AICVD patients without coronary artery disease history. The patients were divided into ACAS ≥50% and non-ACAS ≥50% groups according to whether CTA showed stenosis ≥50% in at least one coronary arterial segment. The AAP characteristics of CTA were depicted from aspects of thickness, extent, and complexity.@*RESULTS@#Among 118 analyzed patients with AICVD, 29/118 (24.6%) patients had ACAS ≥50%, while AAPs were observed in 86/118 (72.9%) patients. Increased AAP thickness per millimeter (adjusted odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.18-2.05), severe-extent AAP (adjusted OR: 13.66, 95% CI: 2.33-80.15), and presence of complex AAP (adjusted OR: 7.27, 95% CI: 2.30-23.03) were associated with ACAS ≥50% among patients with AICVD, independently of clinical demographics and cervicocephalic atherosclerotic stenosis. The combination of AAP thickness, extent, and complexity predicted ACAS ≥50% with an area under the receiver-operating characteristic curve of 0.78 (95% CI: 0.70-0.85, P < 0.001). All three AAP characteristics provided additional predictive power beyond cervical and intracranial atherosclerotic stenosis for ACAS ≥50% in AICVD (all P < 0.05).@*CONCLUSIONS@#Thicker, severe-extent, and complex AAP were significant markers of the concomitant ACAS ≥50% in AICVD, possibly superior to the indicative value of cervical and intracranial atherosclerotic stenosis. As an integral part of atherosclerosis of brain blood-supplying arteries, AAP should not be overlooked in predicting ACAS ≥50% for patients with AICVD.
الموضوعات
Aged , Female , Humans , Male , Middle Aged , Aorta, Thoracic , Pathology , Cerebrovascular Disorders , Diagnosis , Coronary Stenosis , Diagnosis , Cross-Sectional Studies , Odds Ratio , Plaque, Atherosclerotic , Diagnosis , Risk Factorsالملخص
OBJECTIVE: To explore the infection and distribution characteristics of human papillomavirus(HPV)inWuchang district to obtain the epidemic profile and characteristics of HPV in this area.METHODS:Female patients withsexual life history were randomly selected from Wuchang Hospital in Wuhan from July 2013 to June 2018.The patient′scervical exfoliated cells were collected and tested for HPV infection and genotyping.The infection rates of each type ofHPV were calculated and the differences in HPV infections in different age groups were compared.RESULTS:The HPVinfections rate was 18.8%.Among them,high-risk type accounted for 74.9%,significantly higher than low-risk type,accounting for 15.2%.Young women under 30 years old had the highest high-risk and low-risk infection rate(25.8%,21.0%)respectively.HPV 16(20.0%),HPV18(18.0%),and HPV52(14.0%)were top three genotypes among the high-risk types,and HPV11(33.0%),HPV6(32.0%)and HPV CP8304(26.0%)were top three genotypes among the low-risktypes.Among the positive patients,the infection rate of single and double genotype was 76.2% and 18.0%,and somepatients even had five infections.Most of the genotypes could be detected in multiple infected samples except HPV43.CONCLUSION:The prevalence of HPV in women with sexual life history in Wuchang region is 18.8% and it is mainlyhigh-risk infection.The main genotypes are HPV16,HPV18 and HPV52.The high risk population is the young womenunder 30 years old.It is of great clinical significance to strengthen HPV screening and enhance women′s self-testawareness in this region.
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Objective To investigate the feasibility of sequential intensity-modulated radiotherapy (sIMRT)and simultaneously integrated boost intensity-modulated radiotherapy(SIB-IMRT)in the radiotherapy of brain metastasis,the dosimetric difference of target volumes and organs at risk(OARs). Methods Twenty pa-tients diagnosed as brain metastasis were randomly selected,with SIB-IMRT and sIMRT programs developed for each patient. Dosimetric differences between target areas and OARs were compared between the two radiotherapy protocols. Results Compared with sIMRT,SIB-IMRT had no significant difference in the average irradiation dose of the brainstem[(42.69 ± 2.18)Gy vs.(41.98 ± 0.96)Gy]and homogeneity index(HI)(1.46 ± 0.04 vs.1.42 ± 0.13)of P-CTV(P > 0.05). However,SIB-IMRT plan achieved higher than sIMRT in the conformation index (CI)(0.68 ± 0.05 vs. 0.44 ± 0.04)and HI(1.03 ± 0.01 vs. 1.06 ± 0.01)of P-GTV. Meanwhile,both maximum exposure dose of OARs and CI of P-CTV(0.68 ± 0.05 vs.0.44 ± 0.04)of SIB-IMRT were significant in comparison with sIMRT(P<0.05).Conclusions Both radiotherapies can meet target coverage and dose requirements.Com-pared to sIMRT technique,SIB-IMRT technique can decrease effectively the exposure dose of surrounding organs, and can give the tumor target more uniform physical dose conformation.
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Objective To evaluate the clinical value of 99Tcm-Tilmanocept(TMC) SPECT/CT for the detection of SLN by comparing with 99Tcm-sulfur colloid(SC) SPECT/CT. Methods From March 2016 to September 2016, a total of 160 patients (age range: 30-70 years), selected from Breast Surgery Department of Shandong Cancer Hospital, underwent SPECT/CT and planar imaging with either 99Tcm-TMC (TMC group, n=76) or 99Tcm-SC (SC group, n=84). The results of SLN SPECT/CT and planar imaging were compared. The positive rate of SLN in SPECT/CT was compared with operative results. One-way analysis of variance, χ2 test, and two-sample t test were used for data analysis. Results The radiochemical purity of 99Tcm-TMC (≥92%) had no significant difference in 4 h(F=0.720, P>0.05). In TMC group, the average number of SLN detected by SPECT/CT imaging was higher than that by planar imaging (1.34±0.64 vs 0.96±034; t=4556, P0.05). The average number of SLN detected by 99Tcm-TMC imaging was significantly lower than that detected by 99Tcm-SC (t=9.115, P<0.05). The intraoperative detection rates of SLN were 100% (76/76 and 84/84) in both groups. The average number of SLN detected during operation in TMC group was significantly lower than that in SC group (1.89±0.86 vs 3.05±1.29; t=6.642, P<0.01). In TMC group, the average number of SLN detected during operation was significantly higher than that detected by SPECT/CT(1.89±086 vs 1.34±0.64; t=4.492, P<0.05). In SC group, the average number of SLN detected during operation was significantly higher than that detected by SPECT/CT(3.05±1.29 vs 2.57±0.99; t=2.740, P<005). Conclusions SPECT/CT is superior to planar imaging for the detection and localization of SLN. 99Tcm-TMC is suitable for SLN imaging and intraoperative detection.
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In this paper, some items about the microbes listed in the current National Standard of Laboratory Animals were reviewed, including their host spectrum, impact of infection on the animals, their interference on research works and their epidemiology in laboratory animals.This paper may provide some clues for the update of our National Standard of Laboratory Animals.
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The development of laboratory animal science plays a supporting role in the biomedical field, pharmacy and other fields.It is an important symbol to measure the level of science and technology in each countries in the world. The quality of employees directly affects the speed and quality of the development of laboratory animal industry.The purpose of this standard is to regulate the requirements of animal practitioners, to strengthen the training and qualification certification, and to promote the quality of employees.
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Collaborative Cross mice ( CC mice) are series of inbred mice strains generated from hybrid strains of mice with different genetic background which used for human complex diseases and genetic diversity diseases studies. Genetic diversity of CC mice can reflect different mouse subspecies, the single nucleotide polymorphism is four times than traditional inbred mice. CC mice are more and more widely used in the field of life science and medical research. Based on information retrieval of CC mice, we introduced the related information resources of CC mice origin, database, application tools, and research results, to promote CC mice resources to be used widely in China.
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<p><b>BACKGROUND</b>Acute fatty liver of pregnancy (AFLP) is a rare but life-threatening complication occurring in the third trimester. It is often fatal to both mother and fetus. The complicated clinical manifestations as well as an insufficient understanding of the disease make the precise diagnosis and effective treatment of AFLP challenging. A full understanding of the risk factors, clinical features, and test findings of AFLP is critical for its timely diagnosis and treatment.</p><p><b>METHODS</b>We performed a retrospective study of 56 patients with AFLP between June 2008 and July 2013. We analyzed the clinical features, laboratory results, perioperative management, and patient outcomes.</p><p><b>RESULTS</b>The initial symptoms varied considerably, with nausea and vomiting (13/56, 23%) being the most common. Liver-function indexes were remarkable, including elevated levels of serum alanine aminotransferase (262.16 ± 281.71 U/L), aspartate aminotransferase (260.98 ± 237.91 U/L), lactic dehydrogenase (1011.76 ± 530.34 U/L), and direct bilirubin (85.59 ± 90.02 μmol/L). Coagulation disorders were indicated by abnormal levels of fibrinogen (245.95 ± 186.11 mg/dL), D-dimer (2.46 ± 4.01 mg/L), and fibrin degradation products (43.62 ± 48.71 mg/L). The main maternal complications were hypoproteinemia (75%), coagulopathy (54%), and acute renal failure (39%). Multivariate logistic regression analysis identified prothrombin time (PT; odds ratio [OR] = 1.558, 95% confidence interval [CI] =1.248-1.946, PORCIP= 0.009) as risk factors. The perinatal infant death rate was related to gestational age at delivery (ORCI PORCI PORCI PConclusions: Nausea and vomiting may be the most common symptoms of AFLP. Indexes of liver dysfunction and coagulation disorders should also be considered. PT and INR are risk factors for fatal complications in patients with AFLP, and perinatal mortality is linked to the level of fibrin degradation products. Timely delivery is crucial to controlling the development of AFLP.</p>
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Adolescent , Adult , Humans , Middle Aged , Young Adult , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Bilirubin , Metabolism , Fatty Liver , Blood , Metabolism , Pathology , L-Lactate Dehydrogenase , Metabolism , Pregnancy Complications , Blood , Metabolism , Pathology , Retrospective Studiesالملخص
<p><b>OBJECTIVE</b>To study the relationship between the levels of erythropoietin (EPO) in serum and brain injury in preterm infants.</p><p><b>METHODS</b>Three hundred and four preterm infants (gestational age: 28-34 weeks) born between October 2014 and September 2015 were enrolled in this study. Brain injury was diagnosed using cerebral ultrasound and MRI. The levels of EPO, S100 protein, neuron-specific enolase (NSE) and myelin basic protein (MBP) in serum were detected using ELISA. To compare the incidence of brain injury in different serum EPO levels in preterm infants, and the relationship between brain injury and serum EPO levels was analyzed.</p><p><b>RESULTS</b>The incidence rate of brain injury in preterm infants was 41.1% (125/304). The incidence rate of brain injury in the low EPO level group was significantly higher than that in the middle-high EPO level groups (P<0.01). The serum levels of S100 protein, NSE, and MBP in the brain injury groups were significantly higher than in the control group (P<0.01). The serum EPO levels were negatively correlated with serum S100 protein concentration and NSE levels (P<0.05). According to the multiple logistic regression analysis, low gestational age, low birth weight, asphyxia, prolonged mechanical ventilation, anemia and low serum EPO levels were the risk factor for brain injury in preterm infants.</p><p><b>CONCLUSIONS</b>There is a higher incidence rate of brain injury in preterm infants with lower serum EPO levels. The serum EPO levels may be correlated with brain injury in preterm infants.</p>
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Female , Humans , Infant, Newborn , Male , Brain Injuries , Blood , Epidemiology , Erythropoietin , Blood , Infant, Premature , Blood , Myelin Basic Protein , Bloodالملخص
The aim of the present study is to explore the role of miR-124 and its promoter region DNA methylation in homocysteine (Hcy)-induced atherosclerosis. ApoE(-/-) mice were fed with hypermethionine diet for 16 weeks to duplicate hyperhomocysteinemia model. Meanwhile, a normal control group (C57BL/6J mice fed with normal diet, N-control) and a model control group (ApoE(-/-) mice fed with normal diet, A-control) were set. The degree of atherosclerosis was observed by HE and oil red O staining. Automatic biochemical analyzer was used to detect the serum levels of Hcy. Foam cell model was duplicated and oil red O staining was used to confirm whether the model was successfully established. And foam cells were stimulated with 0, 50, 100, 200, 500 μmol/L Hcy and 50 μmol/L Hcy + 10 μmol/L AZC respectively. Real-time quantitative PCR (RT-qPCR) was used to detect the expressions of miR-124 in mice aorta and foam cells; Nested landing methylation specific PCR (nMS-PCR) was used to detect the levels of miR-124 promoter DNA methylation in mice aorta and foam cells. Meanwhile, the effects of DNA methylation inhibitor AZC on miR-124 expression were observed at the cellular level. The effect of miR-124 promoter DNA methylation status on lipid accumulation in foam cells was observed by oil red O staining. The results showed that compared with model control group, the serum levels of Hcy in high methionine group were significantly increased (P < 0.01) and developed aortic atherosclerotic plaque, the expression of miR-124 was markedly decreased (P < 0.01), while the levels of miR-124 promoter DNA methylation were significantly increased (P < 0.01). Given different levels of Hcy, the expression of miR-124 in foam cells was decreased, while the levels of miR-124 promoter DNA methylation were increased in a dose-dependent manner (P < 0.05, P < 0.01). AZC reversed the results of mentioned indices as above markedly (P < 0.05). Downregulation of miR-124 may play a role in Hcy-induced atherosclerosis and its promoter DNA methylation status may be an important mechanism in this process.
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Animals , Mice , Aorta , Metabolism , Apolipoproteins E , Atherosclerosis , Genetics , DNA Methylation , Diet , Foam Cells , Metabolism , Homocysteine , Hyperhomocysteinemia , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs , Genetics , Promoter Regions, Geneticالملخص
Objective To study the significance of No12 lymphadenectomy in patients of advanced distal gastric cancer undergoing D2 distal or total gastrectomy.Methods Clinical and pathological data of 193 distal gastric cancer cases undergoing D2 gastrectomy and No12 lymphadenectomy during Jan 2012 and Jan 2013 were analyzed retrospectively.Results In Borrmann Ⅲ,Ⅳ No.12a LN metastasis was significantly higher than that in Borrmann Ⅰ,Ⅱ (x2 =4.841,P =0.028).In cases of multiple cancer 12a LN metastasis was significantly higher than that in gastric angle,gastric antrum (11.1% 、9.7% 、30.4%).High-differentiated cancer was lower in LN metastasis than that of low differentiated both in No.12a group (x2 =4.292,P =0.038),and in No.12b group (x2 =4.079,P =0.043).In cases with serosal invasion LN metastasis was higher than that without infiltration both in No.12a group (x2 =8.107,P =0.004),and in 12b group (x2 =3.836,P =0.050).In cases of N 0 ~ 1 the LN metastasis was lower than that in N 2 ~ 3 in 12a group (x2 =10.960,P=0.001),12b group (x2 =4.989,P =0.026),and in 12p group (x2 =4.433,P =0.035 respectively).In cases of tumor diameter <3 cm,3 ~5 cm and >5 cm,the 12a lymph node metastasis rate was 4.2%,10.0%,and 29.2%,respectively.Tumor size > 5 cm has higher metastasis rate in No.12a group (x2 =6.464,P =0.011).Conclusions No.12 lymphadenectomy should be included routinely in D2 gastrectomy in patients of distal gastric carcinoma.
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OBJECTlVE To estabIish a simpIe,sensitive and quick method for determination of B7011 in rat pIasma. METHODS The method of protein precipitation with methanoI was used for pre-treatment of pIasma sampIes determined by Iiquid chromatography mass spectrometer. The Iinear reIa-tionship,intra-batch and inter-batch precision,specificity,matrix effect,recovery rate,the accuracy and stabiIity of the pIasma sampIes were vaIidated. The concentration of B7011 in pIasma was determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. RESULTS The Iinear range of B7011 was 30-20 000 μg·L-1 ,the Iower Iimit of quantification was 30 μg·L-1 in pIasma,the in-tra-batch precision of 60,1000,16 000 and 10 000 ng·mL-1 was 5.61% -13.31%,2.31% -8.35%, 2.02%-9.47% and 4.0%-15.0% respectiveIy,and inter-batch precision was 10.05%,2.55%,3.75% and 8.58% respectiveIy. The recovery of 60,1000,and 16 000 μg·L-1 was 114.12%,109.2% and 101.06%respectiveIy. The average peak concentrations were 8373.28 and 8564.59 μg·L-1 ,the mean AUC was 98 400 and 104 000 μg·L-1·h and the t1/ 2z for B7011 was 41.7 and 63.6 h in bIood of maIe and femaIe rats, respectiveIy. CONCLUSlON The estabIished method is sensitive, fast and simpIe and concentration of B7011 in pIasma is determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. It can satisfy the requirements of pharmacokinetic and toxicokinetic studies.
الملخص
<p><b>OBJECTIVE</b>This study aimed to evaluate the effectiveness of multi-disciplinary treatment approaches in reducing neurological disabilities in premature infants.</p><p><b>METHODS</b>A total of 117 infants who were born premature in our hospital between March 2008 and February 2010 but had no congenital malformations and no severe neonatal complications, were enrolled in this study. They were randomly allocated to a multi-disciplinary treatment group (n=63) and a control group (n=54). While patients in the control group underwent an early conventional treatment, those in the multi-disciplinary treatment group were subjected to regular development monitoring, neurological examination and screening for brain injury, neuro-nutrition and neurodevelopment therapies, and rehabilitation training.</p><p><b>RESULTS</b>The incidence rates of abnormalities in posture, reflex, sleep, muscle tone and EEG were significantly lower in the multi-disciplinary treatment group than in the control froup (P<0.05) at corrected postnatal ages of 6-12 months. At corrected postnatal ages of 6, 12, 18 and 24 months, both mental development index (MDI) and psychomotor development index (PDI) scores were significantly higher in the multi-disciplinary treatment group than in the control group (P<0.05). At corrected postnatal age of 3 years, incidence rates of cerebral palsy, language barrier, abnormal muscle tone and hearing impairment were significantly lower in the multi-disciplinary treatment group than in the control group (P<0.05).</p><p><b>CONCLUSIONS</b>Early multi-disciplinary intervention approaches may significantly improve mental and motor developments and reduce the incidence of cerebral palsy-associated neurological disabilities in premature infants.</p>
الموضوعات
Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Cerebral Palsy , Developmental Disabilities , Infant, Premature , Infant, Premature, Diseasesالملخص
Herb combination has been very popular in traditional medical prescriptions such as Traditional Chinese Medicine [TCM]. Persistent efforts and attempts have been made to dissect the action mode of TCM in recent years, which has provided certain evidence for inter-herbal interactions. However, the interactions among different components in a single herb have been largely neglected. In this experimental study, the interactions among different components of a single herb were explored. The effect of three main sesquiterpenes [germacrone, curdione, furanodiene] isolated from Curcuma WenyujinY.H. Chenet C Ling on MDA-MB-231 and MCF-7 breast cancer cell proliferation alone or in combination with a fixed-dose-combination was investigated. Furanodiene significantly inhibited cancer cell proliferation while germacrone and curdione showed no effect. Germacrone enhanced furanodiene's anti-proliferative effect. Curdione showed no effect on furanodiene's anti-proliferative effect but partly reversed the anti-proliferative effect of germacrone and furanodiene combined. The morphological and mitochondrial membrane potential [delta [PSI]m] changes showed similar results. However, they demonstrated complicated interactions on the expression of apoptotic-related proteins and key signal transduction proteins. Unpredictable and complex interactions among different components in Curcuma WenyujinY.H.Chenet C Ling may exist. The intra-herb interactions should be taken into consideration when attempts are made to interpret the art of TCM formulation or other similar recipes
الموضوعات
Humans , Sesquiterpenes, Germacrane , Furans , Heterocyclic Compounds, 2-Ring , Cell Proliferation , Herb-Drug Interactions , Medicine, Chinese Traditionalالملخص
<p><b>BACKGROUND</b>The level of c-Myc is closely associated with high pathological grade and the poor prognosis of gliomas. Vascular endothelial growth factor (VEGF) is the most important angiogenic factor that potently stimulates the proliferation and migration of vascular endothelial cells. This study aimed to address the biological importance of c-Myc in the development of gliomas, we downregulated the expression of c-Myc in the human glioblastoma cell line IN500 and studied the in vitro effect on cellular growth, proliferation, and apoptosis and the expression of VEGF and the in vivo effect on tumor formation in a xenograft mouse model.</p><p><b>METHODS</b>IN500Δ cells were stably transfected with shRNA-expressing plasmids for either c-Myc (pCMYC-shRNA) or as a control (pCtrl-shRNA). Following establishment of stable cells, the mRNA expressions of c-Myc and VEGF were examined by reverse transcription (RT)-PCR, and c-Myc and VEGF proteins by Western blotting and immunohistochemistry. Cell-cycle progression and apoptosis were determined by flow cytometry. The in vivo effect of targeting c-Myc was determined by subcutaneous injection of stable cells into immunodeficient nude mice.</p><p><b>RESULTS</b>The stable transfection of pCMYC-shRNA successfully knocked down the steady-state mRNA and protein levels of c-Myc in IN500, which positively correlated with the downregulation of VEGF. Downregulating c-Myc in vitro also led to G1-S arrest and enhanced apoptosis. In vivo, targeting c-Myc reduced xenograft tumor formation and resulted in significantly smaller tumors.</p><p><b>CONCLUSIONS</b>c-Myc has multiple functions in glioblastoma development that include regulating cell-cycle, apoptosis, and VEGF expression. Targeting c-Myc expression may be a promising therapy for malignant glioma.</p>