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@#[摘 要] 目的：基于蛋白质组学技术探讨麻疹减毒活疫苗191株（MV-Hu191）在体内外对三阴性乳腺癌MDA-MB-231、4T1细胞的影响及其作用机制。方法：采用CCK-8法检测MV-Hu191对MDA-MB-231和4T1细胞增殖的影响；液相色谱-质谱联用技术分析MV-Hu191处理对MDA-MB-231细胞中蛋白质谱的影响，多重数据库筛选蛋白质谱中的典型差异蛋白质并进行GO、KEGG、亚细胞定位与功能注释。瘤内注射1×106 TCID50 MV-Hu191干预4T1细胞移植瘤模型小鼠，流式细胞术检测小鼠脾组织中T细胞亚群，ELISA法检测小鼠血清TNF-α和IL-6含量。结果：体外实验结果表明，MV-Hu191具有抑制MDA-MB-231和4T1细胞增殖的作用，差异均具有统计学意义（P<0.01）。蛋白质组学分析结果显示，MV-Hu191作用MDA-MB-231细胞后明显上调蛋白质有38个、下调有12个；差异表达的蛋白质主要参与细胞黏附、信号受体激活、细胞代谢、应激反应等生物学过程，22个差异蛋白质亚细胞定位位于细胞外，KEGG功能分类显示与免疫调节功能相关的差异蛋白质最多且均为上调蛋白，包括C4A、C8B、SERPINF2、A2M、SERPINC1、CTSB、SERPING1、C5；PPI预测发现免疫相关差异蛋白与CD4、CD8、TNF-α及IL-6相互关联。体内实验结果显示，MV-Hu191干预组小鼠脾组织中CD4+ T细胞数量略高于对照组，但差异无统计学意义（P>0.05），CD4+/CD8+ T细胞比值明显高于对照组（P<0.05），血清TNF-α和IL-6含量显著上升（均P<0.01）。结论：MV-Hu191显著抑制MDA-MB-231、4T1细胞增殖及拮抗4T1细胞荷瘤小鼠成瘤性，其机制可能是MV-Hu191通过激活免疫效应分子实现抗肿瘤作用。
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Objective@#To investigate the characteristics of dead HIV/AIDS cases within 1 year after confirmatory testing in Jingzhou City, Hubei Province from 1996 to 2021, so as to provide the evidence for facilitating early identification and treatment of AIDS.@*Methods@#The basic and follow-up data of HIV/AIDS cases were retrieved from the HIV/AIDS Comprehensive Response Information System of Chinese Disease Prevention and Control Information System, and mortality density and its trend were evaluated within 1 year after confirmatory testing. The factors affecting death within 1 year after confirmatory testing were identified using a Cox proportional hazards model, and the demographics, detection, treatment and cause of death were analyzed among dead HIV/AIDS cases within 1 year after confirmatory testing.@*Results@#A total of 3 304 HIV/AIDS cases were included, with 508 deaths within 1 year after confirmatory testing. The overall mortality density was 17.43 per 100 person-years, and the mortality density appeared a tendency towards a reduction from 1996 to 2021 (χ2trend=21.053, P<0.001). Of all dead HIV/AIDS cases within 1 year after confirmatory testing, 77.76% were men, 67.72% at ages of 45 years and older, 83.86% with transmission by heterosexual contact, 83.66% identified in medical institutions, 62.20% without antiretroviral therapy, and 47.83% without detection of CD4+T cell count. Mortality that was not associated with AIDS was the predominant cause of death among dead HIV/AIDS cases within 1 year after confirmatory testing (58.86%). Age of 30 years and older (HR: 1.781-4.644, 95%CI: 1.073-7.784), identification in medical institutions (HR=2.130, 95%CI: 1.306-4.474), initial CD4+T cell count of <200 cells/μL (HR: 2.649-12.879, 95%CI: 1.669-19.189), no antiretroviral therapy (HR=7.945, 95%CI: 5.743-10.993) and initiation of antiretroviral therapy 4 to 12 months after confirmatory testing (HR=1.636, 95%CI: 1.005-2.662) resulted in a higher risk of mortality within 1 year after confirmatory testing.@*Conclusions@#The mortality density appeared a tendency towards a reduction among cases within 1 year after confirmatory testing in Jingzhou City from 1996 to 2021. Mortality within 1 year after confirmatory testing was associated with advanced age, heterosexual contact transmission, identification in medical institutions, low CD4+T cell counts, and delay or absence of antiretroviral therapy.
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This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure.
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@#Abstract: Objective To investigate the occurrence of multidrug-resistance among tuberculosis patients in Hainan Province from 2014 to 2020 and to analyze the influencing factors, aiming to provide reference for formulating drug-resistant tuberculosis control strategies in this region. Methods This study collected sputum samples from the patients with pulmonary tuberculosis admitted to the Second Affiliated Hospital of Hainan Medical University from 2014 to 2020, and performed isolation and identification of Mycobacterium tuberculosis and drug susceptibility testing. After the strains were identified as positive, drug sensitivity tests were conducted, and multi-drug resistant patients were found. Clinical data was retrospectively collected, and chi-square test and unconditioned logistic regression were used to analyze the influencing factors of multidrug resistance. Results A total of 2 672 patients underwent sputum culture, strain identification, and drug susceptibility testing in TB designated hospitals in Hainan Province from January 1, 2014 to December 31, 2020. Among them, 1 942 patients with available drug susceptibility test results and complete clinical data were enrolled, among which 398 cases with drug-resistant TB were included in the case group, and 1 544 cases without drug resistance were included in the control group. Multivariate logistic regression analysis showed that farmers, rural residence, treatment history of retreatment, irregular medication history, number of pulmonary cavities ≥3, and BMI<18.5 were independent risk factors for MDR-TB. The risk of MDR-TB in farmers was higher than that in non-farmers (OR=1.542, 95%CI: 1.150-2.020); patients living in rural areas had a higher risk of multidrug resistance than those living in urban areas (OR=1.445, 95%CI: 1.095-1.907); the risk of MDR in the retreatment patients was higher than that in the initial treatment patients (OR=5.616, 95%CI: 4.250-7.421); the risk of multi-drug resistance in patients with irregular medication was higher than that in patients with regular medication (OR=2.665, 95%CI: 2.012-3.531); the risk of multidrug resistance in patients with pulmonary cavity number ≥3 was higher than that in patients with pulmonary cavity number <3 (OR=5.040, 95%CI: 3.768-6.740); compared with patients with BMI<18.5, patients with BMI=18.5-24.0 and BMI≥24.0 had a lower risk of multidrug resistance (OR=0.735, 95%CI: 0.555-0.975 and OR=0.447，95%CI:0.225-0.888, respectively). Conclusions Retreatment, farmer occupation, rural residence, irregular medication and low BMI may be the risk factors for multidrug resistance in Hainan Province.
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@#Abstract: Objective To investigate the type and distribution of drug resistance of Mycobacterium tuberculosis (MTB) in Hainan tuberculosis hospital from 2019 to 2021, and to provide reference for the development of drug resistant tuberculosis prevention and control strategy. Methods From 2019 to 2021, a total of 1 687 strains of sputum were isolated and cultured and identified as MTB. Drug sensitivity testing was performed on eight anti-tuberculosis drugs: isoniazid (INH), rifampicin (RFP, R), ethambutol (EMB), streptomycin (SM), kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), and propylthioisoniacamide (PTO). The drug resistance analysis was conducted. Results Among the 1 687 MTB strains, the overall drug resistance rate was 41.32% (697), with a single drug resistance rate of 11.62% (196), a multi-drug resistance rate of 4.10% (69), a extensive drug resistance rate of 23.71% (400), a pan-drug resistance rate of 1.90% (32), and a rifampicin resistance rate of 28.10% (474), and the main drug resistance types were extensive drug resistance and rifampicin resistance. The order of resistance to the eight drugs was OFX (64) > SM (62) > INH (48) > RFP (19) > CPM (2) > KM (1) > EMB (0) and PTO (0). The rate of resistance to INH and RFP of first-line drugs in newly treated patients was lower than that in retreated patients (χ2=0.110, 0.765; P>0.05); the rate of resistance to second-line drugs OFX, CPM and KM in initially treated patients was lower than that in retreated patients (χ2=1.037, 1.212, 1.653; P>0.05). The total drug resistance rate in 2019 was 51.16%, which was higher than that in 2020 (35.08%) and 2021 (38.89%). The difference between groups was significant (χ2=29.25,16.60; P=0.000), but there was no significant difference in overall drug resistance rate between 2020 and 2021 (χ2=1.823, P=0.177). Among the occupational types of tuberculosis patients, farmers were the main ones, accounting for 56.25% (949). The patients with drug-resistant tuberculosis were mainly distributed in Haikou City (165) > Wanning City (72) > Chengmai County(64) > Wenchang City (51) = Dongfang City (51) > Danzhou City (48), and patients in these six areas accounting for 64.71%(451/697). Conclusions The drug resistance rate of tuberculosis in Hainan Province is relatively high, with OFX and SM resistance being the main types of drug resistance. The extensive drug resistance rate is higher than the national average level. Therefore, surveillance and treatment should be strengthened and optimized to reduce the prevalence of drug-resistant tuberculosis.
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Objective@#To investigate the trend in incidence of hepatitis C in Jingzhou City, Hubei Province from 2008 to 2022, and to examine the age-period-cohort effect, so as to provide the basis for the formulation of hepatitis C prevention strategies. @*Methods@#Demographic data and incidence data of hepatitis C in Jingzhou City from 2008 to 2022 were collected through the Chinese Disease Prevention and Control Information System, and the trend in incidence of hepatitis C was analyzed using average annual percent change (AAPC) and annual percent change (APC). The effects of age, period and cohort on the incidence of hepatitis C were examined with an age-period-cohort model. @*Results@#The average annual incidence of hepatitis C in Jingzhou City from 2008 and 2022 was 20.26/105, with a male incidence of 20.04/105 and a female incidence of 20.47/105. The incidence of hepatitis C initially rose and then fell (AAPC=5.375%, P<0.05), with a rising trend from 2008 to 2018 (APC=13.370%, P<0.05) and a decreasing trend from 2018 to 2022 (APC=-12.231%, P<0.05). The incidence of hepatitis C appeared a tendency towards a rise with age, and the 80-84 age group had the highest risk (RR=11.420, 95%CI: 7.631-17.090) in relative to the 45-49 age group. The incidence of hepatitis C appeared a tendency towards a rise followed by a decline with time, and an increased risk of hepatitis C was seen from 2013 to 2017 (RR=1.393, 95%CI: 1.272-1.525) and a decreased risk was seen from 2018 to 2022 (RR=1.237, 95%CI: 1.072-1.428) in relative to the period from 2008 to 2012. The incidence of hepatitis C appeared a tendency towards a rise followed by a decline with the cohort, and a higher risk was found in the 1965-1984 cohort (all RR>1.300) in relative to the 1960-1964 cohort. The incidence of hepatitis C, the age and period effects in men and women, and the cohort effects in men were consistent with the whole population. In addition to the 1965-1984 cohort, a higher risk was found in the 2000-2014 cohort in women (all RR>1.250).@*Conclusions@#From 2008 to 2022, the incidence of hepatitis C in Jingzhou City experienced a notable rise and subsequent decline. The incidence of hepatitis C increased with age, with higher risks seen among middle-aged and elderly people.
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Fluorescence imaging is a noninvasive and dynamic real-time imaging technique;however,it exhibits poor spatial resolution in centimeter-deep tissues because biological tissues are highly scattering media for optical radiation.The recently developed ultrasound-controlled fluorescence(UCF)imaging is a novel imaging technique that can overcome this bottleneck.Previous studies suggest that the effective contrast agent and sensitive imaging system are the two pivotal factors for generating high-resolution UCF images ex vivo and/or in vivo.Here,this review highlights the recent advances(2015-2020)in the design and synthesis of contrast agents and the improvement of imaging systems to realize high-resolution UCF imaging of deep tissues.The imaging performances of various UCF systems,including the signal-to-noise ratio,imaging resolution,and imaging depth,are specifically discussed.In addition,the challenges and prospects are highlighted.With continuously increasing research interest in this field and emerging multidisciplinary applications,UCF imaging with higher spatial resolution and larger imaging depth may be developed shortly,which is expected to have a far-reaching impact on disease surveillance and/or therapy.
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Objective@#To explore the relationship between sleep and exercise among grade 1-6 students in a certain city during the period of home based online courses in the epidemic, and to provide reference basis for the government and relevant departments to make relevant policies on student health promotion.@*Methods@#From April 22 to May 14 in 2020, 24 452 primary school students were selected by stratified cluster random sampling method to network questionnaire survey, which included general situation, sleep time,and exercise.@*Results@#Totally 21.6% of primary school students participated in low intensity exercise, 9.4% in moderate intensity exercise and 5.8% in high intensity exercise every day. Less than 10% of the students participated in all types of intense sports for more than 30 minutes each time. The report rate of sleep deprivation among students in grades 1 to 6 was 22.5%, 25.5%, 28.9%, 31.3%, 35.0%, 39.9%, respectively(χ 2=350.75, P<0.05). Multivariate Logistic regression analysis showed that after adjusting for gender, grade, oneness and other factors, high intensity exercise was negatively correlated with sleep deprivation(OR=0.91, 95%CI=0.86-0.97).@*Conclusion@#Insufficient sleep is common among primary students, and appropriate amount of high intensity exercise is a favorable factor to ensure adequate sleep time in primary school students.
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@#[Abstract] Objective: To explore whether gambogic acid can enhance the sensitivity of glioma U251 cells to temozolomide and further explore its mechanism. Methods: U251 cells were cultured in vitro and divided into blank control group, gambogic acid treatment group, temozolomide alone treatment group and combined treatment group. The cells survival rates of cells in each group was detected by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and changes in ROS level. Western blotting was used to detect the changes in protein expressions. Results: CCK-8 results showed that the cells survival rates of the four groups after treatment for 24 h were (98.65±3.68)%, (93.58±2.47)%, (66.81±2.39)% and (38.65±4.13)%, respectively. It can be seen that the combined treatment could significantly increase the inhibitory effect of temozolomide on U251 cells. The proportion of apoptotic U251 cells in the combined treatment group was (61.43±2.58)%, which was significantly higher than that of (26.68±1.82)% in the temozolomide-treated group. Combined treatment of gambogic acid and temozolomide could up-regulate ROS level in U251 cells, reduce the expressions of GLUT-3 and p-AKT, and inhibit the GLUT-3/AKT signaling pathway. Conclusion: Gambogic acid combined with temozolomide can enhance the sensitivity of U251 cells to temozolomide by up-regulating ROS level and inhibiting GLUT-3/AKT signaling pathway in U251 cells, and provides a theoretical basis for the application of gambogic acid in the treatment of glioma.
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Objective@#To investigats the specific changes of brain neuron oscillation in non-clinical high-trait anxiety college students by recording the resting state EEG of high and low trait anxiety subjects.@*Methods@#College students in a university were administered by using the S-TA Inventory, 27% of the number of people before and after the selection were divided into low-specific focus group (15) and high-trait anxiety group(15), based on the STAT score. After pre-processing, the data was divided into five frequency bands of δ(1-<4), θ(4-<8), α(8-<13), β(13-<30), γ(30-100)Hz and every electrode power value of those was calculated respectively. Correlation between power spectrum and trait anxiety scores was investigated.@*Results@#The high-trait anxiety group were in the frontal and central regions (t=3.47, 2.62) of the δ band, the frontal region (t=2.22) of the θ band, the frontal, central, right temporal, and posterior regions (t=2.77, 2.23, 3.65, 2.35) of the β band, the frontal, left temporal, central, right temporal, and posterior regions (t=2.83, 2.22, 2.64, 2.43, 2.09) of the γ band, than that in the low trait anxiety group. Furthermore, in central regions of the δ band; the frontal region of the θ band; the frontal, the central, and posterior regions of the β band; the frontal, left temporal, central, and posterior regions(r=-0.63, -0.51, -0.62, -0.53, -0.54, -0.59, -0.56, -0.55, -0.49) of the γ band, the correlation between trait anxiety scores and the power value were obvious negatively.@*Conclusion@#High trait anxiety college students have lower power spectrum than low trait anxiety college students. The degree of trait anxiety is related to the power spectrum. The changes of brain resting-state electrical signals in high-trait anxiety individuals may be related to the influence of trait anxiety on college students’ attention and working memory.
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ABSTRACT This study aimed to investigate the expression and mechanism of N- methyl -D- aspartate receptor 1 (NMDAR1) in the pathogenesis of Alzheimer disease (AD). Eighty adult Wistar rats were randomly divided into 4 groups (n=20 each) to receive an injection of 0, 5, 7 and 10 μl of 1 μg/μl amyloid-β 42 (Aβ1-42) in the hippocampus. Twenty rats in normal control group were injected with equal volume of saline. After 10 days, the hippocampus was isolated from 5 randomly selected rats in each group. The NMDAR1 protein and mRNA expression was determined by immunohistochemical staining and qRT-PCR. The aquaporin-1 (AQP-1) mRNA expression was also measured by qRT-PCR. We found that both NMDAR1 and AQP-1 expression in Aβ1-42 groups was increased in a dose-dependent manner. NMDAR1 and AQP-1 expression in 7 and 10 μl Aβ1-42 groups was significantly higher compared with 0 μl Aβ1-42 group (P <0.01). Further, the 10 μl Aβ1-42 group was randomly divided into 3 subgroups: AD-NMDA, AD-MK-801, and AD-Ctrl subgroup, which was given an intraperitoneal injection of NMDAR agonist NMDA, NMDAR antagonist MK-801 and saline, respectively. The relative APQ-1 expression in each subgroup was determined by qRT-PCR and Western blot analysis after 24 h. The AQP-1 expression was significantly decreased in AD-MK-801 group (P < 0.05), but was markedly increased in AD-NMDA group when compared with AD-Ctrl group (P <0.01). Our study suggested that expression abnormity of NMDAR1 is involved in the pathogenesis of AD. NMDAR1 might regulate the pathogenic process through stimulating the expression of AQP-1.
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BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.