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Objective:To investigate the effects of artesunate ( ART ) on neuronal apoptosis, inflammatory response after stroke in rats and microglia polarization.Methods:(1)Animal experiment: twenty-seven male SD rats of SPF grade were divided into sham operation group, model group and ART treatment group according to the random number table method, with 9 rats in each group.Rats in the model group and ART treatment group were used to establish a stroke model by middle cerebral artery occlusion (MCAO). And rats in the ART treatment group were intraperitoneally injected with ART (25 mg/kg) once a day for three days before modeling, while the rats in sham operation group and the model group were injected with the same amount of solvent.And 24 h after the modeling, TTC staining was used to evaluate the volume of cerebral infarction, Western blot was used to detect the expression of Bcl2 in the infarct area, penumbra and hippocampus, TUNEL method was used to detect neuronal apoptosis, and tissue immunofluorescence was used to observe the expression of tumor necrosis factor-α(TNF-α) in the penumbra region of cerebral cortex.(2)Cell experiments: microglia BV2 were cultured and divided into control group, oxygen-glucose deprivation/reoxygenation group, oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group.The levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β) and TNF-α were detected by qRT-PCR, the expressions of M2 type microglia marker protein CD206 and ARG1 were detected by Western blot, the BV2 cell medium after treatment in each of the above groups was collected as conditioned medium to culture HT22 hippocampal neuron cells and cell activity was measured by CCK8 method.GraphPad Prism 7 software was used for data analysis.One-way ANOVA was used for comparison of differences among multiple groups, and LSD was used for further two-by-two comparisons.Results:(1)Animal experiment results: TTC staining results showed that the percentage of cerebral infarction volume in the ART treatment group was smaller than that in the model group ((23.09±8.51)%, (39.63±5.71)%, t=33.93, P<0.01). The results of TUNEL staining showed that the number of apoptotic cells in the model group and ART treatment group was higher than that in the sham operation group ((638.90±177.82)cells/mm 2, (72.75±13.21) cells/mm 2, (16.16±2.73) cells/mm 2, both P<0.05), and the number of apoptotic cells in the ART treatment group was lower than that in the model group ( P<0.05). Western blot results showed that the levels of Bcl2 protein in penumbra and infarct area of the model group were both lower than those in sham group(both P<0.05). The levels of Bcl2 protein in penumbra, the hippocampus and infarcted area of the ART treatment group were significantly lower than those of the model group(all P<0.05). The results of tissue immunofluorescence showed that the fluorescence intensities of TNF-α in the model group and ART treatment group were higher than those in the sham group (all P<0.05), while the fluorescence intensity of TNF-α in the ART treatment group was lower than that in the model group ( P<0.05). (2)Cell experiment: qRT-PCR results showed that compared with the control group, the mRNA levels of IL-6, IL-1β and TNF-α (all P<0.05) in oxygen-glucose deprivation/reoxygenation group were significantly higher than those of the control group.And the mRNA levels of IL-1β, IL-6 and TNF-α in oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group were significantly lower than those of the oxygen-glucose deprivation/reoxygenation group (all P<0.05). Western blot results showed that compared with the control group, the expression of CD206 ((0.85±0.04), (1.07±0.07), P<0.05) was significantly down-regulated in the oxygen-glucose deprivation/reoxygenation group.The CD206 and ARG in oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group((1.22±0.06), (1.35±0.08)) and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group((1.24±0.14), (1.14±0.07)) were significantly higer than those of oxygen-glucose deprivation/reoxygenation group((0.85±0.04), (0.85±0.05))(all P<0.05). The results of CCK8 showed that compared with the control group, the cell viability in the oxygen-glucose deprivation/reoxygenation group was significantly decreased( P<0.05). The cell viability of the oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, the oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group, the oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group were all higher than those of oxygen-glucose deprivation/reoxygenation group(all P<0.05). Conclusion:ART reduces neuronal apoptosis after stroke, decreases the neuroinflammatory response after stroke, and promotes oxygen-glucose deprivation/reoxygenation-activated microglia BV2 polarization to the M2 type.
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Objective:To explore the levels of programmed death receptor 1 (PD-1) and lymphocyte activating gene 3 (LAG-3) in the immune microenvironment of diffuse large B-cell lymphoma (DLBCL), their relationship with clinicopathological features, and their impact on prognosis.Methods:The tumor tissue sections and formaldehyde fixed paraffin embedded tissues from 174 DLBCL patients diagnosed at the First Affiliated Hospital of Xinjiang Medical University from February 2012 to August 2017 were retrospectively collected. The tissue chips were prepared, and the immunohistochemistry (IHC) method was used to detect the expressions of PD-1 and LAG-3 proteins in tumor infiltrating lymphocytes (TIL) of tissue chips [including whether they were positive (positive for IHC score 1-9 points, negative for 0 point) and expression level (high expression was 4-9 points on IHC score, low expression was 0-3 points)]. The relationship between the expression levels of PD-1 and LAG-3 and the clinicopathological characteristics of patients was analyzed. Spearman correlation coefficient was used to analyze the correlation between the expression levels of PD-1 and LAG-3. Kaplan-Meier method was used to draw overall survival (OS) and progression free survival (PFS) curves of patients with different expression levels of PD-1 and LAG-3, and log-rank test was used for comparison between the groups. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of OS and PFS in patients.Results:Of the 174 DLBCL patients, 95 (54.6%) were male and 79 (45.4%) were female; the median age was 60 years old (5-87 years old). The proportions of patients with PD-1 and LAG-3 positive in TIL of tumor tissues were 79.3% (138/174) and 78.8% (137/174), and the proportions of patients with high expression were 35.6% (62/174) and 37.9% (66/174), respectively. Among patients with bone marrow involvement, the proportion of patients with high expression of PD-1 [62.5% (15/24) vs. 32.5% (39/120), P= 0.006], the proportion of patients with high expression of LAG-3 [54.2% (13/24) vs. 32.5% (39/120), P= 0.050] were higher than those without bone marrow involvement. The expression levels of PD-1 and LAG-3 were not associated with gender, age, clinical stage, international prognostic index score, functional status (PS) score, lactate dehydrogenase level, whether there were B symptoms, whether it was intranodal, tumor length, whether it was germinal center B cell type, number of extranodal involvement sites, and whether it was treated with R-CHOP regimen (all P > 0.05). There was a positive correlation between PD-1 and LAG-3 expression levels in TIL of tumor tissues ( r = 0.202, P = 0.008). Multivariate Cox regression analysis showed that PS score (>2 points vs. ≤2 points: HR = 5.458, 95% CI 2.082-14.307, P = 0.001), R-CHOP regimen treatment (no vs. yes: HR = 2.181, 95% CI 1.086-4.379, P = 0.028) were independent influencing factors of OS, and PS score (>2 points vs. ≤2 points: HR = 3.913, 95% CI 1.579-9.698, P = 0.003), R-CHOP regimen treatment (no vs. yes: HR = 2.609, 95% CI 1.412-4.819, P = 0.024), LAG-3 expression level (low expression vs. high expression: HR = 0.531, 95% CI 0.283-0.995, P = 0.048) were independent influencing factors of PFS. There were no statistical differences in PFS and OS between patients with high and low PD-1 expression levels in TIL (both P > 0.05). PFS and OS in patients with high LAG-3 expression were worse than those in patients with low expression (both P < 0.05). OS in patients with high expressions of PD-1 and LAG-3 was worse than that in patients with low expressions of PD-1 and LAG-3 ( P = 0.044). Conclusions:The expression levels of PD-1 and LAG-3 in TIL of DLBCL patients' tumor tissues are related to bone marrow involvement, which are not related to most other clinicopathological features, and the prognosis of patients with high expressions of PD-1 and LAG-3 is poor.
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Objective To investigate the clinical effect of pars plana vitrectomy combined with segmental scleral buckling(PPV-SSB)in the treatment of inferior rhegmatogenous retinal detachment(RRD).Methods Totally 87 eyes of 87 patients with inferior RRD who attended the Ophthalmology Department Ⅱ,the First Affiliated Hospital of Zhengzhou University from October 2020 to April 2022 were retrospectively included.Among them,45 patients(45 eyes)were treated with PPV-SSB(PPV-SSB group),and 42 patients(42 eyes)were treated with PPV(PPV group).The retinal reattachment rate,best corrected visual acuity(BCVA)and complications of patients who underwent single surgery in the two groups were compared.Results After a single surgery,the retinal reattachment rate was 95.56％(43/45)in the PPV-SSB group and 80.95％(34/42)in the PPV group,with a statistically significant difference(P=0.033).At 3 months and 6 months af-ter surgery,there were significant differences in BCVA between the PPV-SSB group and the PPV group(P=0.010,0.004).The incidence of postoperative phacoscotasmus in the PPV-SSB group and the PPV group was 28.89(13/45)and 54.76％(23/42),respectively,with a significant difference(P=0.018),while there were no significant differences in the inci-dence of the remaining few complications(all P＞0.05).Conclusion PPV-SSB has a higher retinal reattachment rate,better visual effect and fewer complications in the treatment of inferior RRD.
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Objective@#To analyze physical fitness and health status and gender differences of middle school students among 5 minorities (Mongolian, Hui, Uyghur, Zhuang and Korean), and to provide the theoretical basis for the strategy formulation.@*Methods@#The present data came from 3 waves of Chinese National Survey on Students Constitution and Health (2010, 2014, and 2019). According to National Standards for Students Physical Health (2014 Revision), excellent, and excellent good physical fitness and health status were defined. Cochran Armitage test was used to examine the trends of physical fitness and health status. Chi square test and Logistic regression were used to analyze the difference of physical fitness and health status by sex and survey year.@*Results@#From 2010 to 2019, the excellent physical fitness and health status rate of Mongolian, Hui, Uyghur, Zhuang and Korean students increased from 1.8%, 0.7%, 0.3%, 0.5% and 1.3% to 4.3%, 2.8%, 1.2%, 1.3% and 3.5%, respectively. The excellent good physical fitness and health status rate of Mongolian, Hui, Uyghur and Zhuang students increased from 12.9%, 8.0%, 7.2 % and 8.4% to 24.7%, 20.1%, 12.6% and 19.8%( Z =6.15，6.71，4.12，3.06，5.26；11.88，13.42，6.70，11.08， P <0.05), respectively. In 2019, students aged 13 to 15 years showed higher proportion of excellent/excellent good physical fitness and health status than that of students aged 16 to 18. Boys were more likely to be in excellent/excellent good physical fitness and health status than girls from 2010 to 2019. The sex difference in excellent/excellent good physical fitness and health status narrowed during 2010 and 2019.@*Conclusion@#Physical fitness and health status of minority students improved while sex difference narrowed during last decade, but there is still a long way to reach the goal proposed by China. Targeted intervention should be proposed to promote physical fitness and health status in accordance with the developmental characteristics, especially for girls and students aged 16 to 18 years.
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DNA methylation is one of the key epigenetic regulatory mechanisms in development and spermatogenesis. However, the dynamic regulatory mechanisms of genome-wide DNA methylation during testicular development remain largely unknown. Herein, we generated a single-base resolution DNA methylome and transcriptome atlas of precocious porcine testicular tissues across three developmental stages (1, 75, and 150 days old). The results showed that the dynamic methylation patterns were directly related to the expression of the DNMT3A gene. Conjoint analysis revealed a negative regulatory pattern between promoter methylation and the positive regulation of 3'-untranslated region (3'UTR) methylation. Mechanistically, the decrease in promoter methylation affected the upregulation of meiosis-related genes, such as HORMAD1, SPO11, and SYCE1. Demethylation in the 3'UTR induced the downregulation of the INHBA gene and knockdown of INHBA inhibited cell proliferation by reducing the synthesis of activin A. These findings contribute to exploring the regulatory mechanisms of DNA methylation in testicular development.
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Metilación de ADN , Epigénesis Genética , Regiones no Traducidas 3' , Animales , ADN , Epigenoma , Masculino , Regiones Promotoras Genéticas , PorcinosRESUMEN
【Objective】 In this study， reactive oxygen species （ROS） scavenger N-acetyl-L-cysteine （NAC） was used to explore the inhibitory effect and mechanism of artesunate （ART） on pancreatic carcinoma （PC） cells. 【Methods】 Different concentrations of ART interfered with 3 PC cell lines CFPAC-1， Capan-2 and BxPC3. Cell viability was measured by CCK8； cell migration ability was measured by Transwell method， and the expressions of migration-related proteins E-cadherin， N-cadherin and Vimentin were measured by Western blotting. ROS probe DCFH-DA was used to measure intracellular ROS； LC3 cell immunofluorescence （IF） was used to detect the formation of intracellular autophagosomes. After adding NAC or autophagy inhibitor 3-MA， the cell viability was tested again by CCK8， and the expressions of p-AMPK/ AMPK， p-mTOR/mTOR， p62 and LC3Ⅱ/Ⅰ were detected by Western blotting. 【Results】 ART inhibited the growth of CFPAC-1 and Capan-2 in a time- and dose-dependent manner. After treatment of CFPAC-1 and Capan-2 cells with 200 μmol/L of ART for 48 h， the expression of E-cadherin was upregulated， while N-cadherin and Vimentin were downregulated， and the cell migration ability was significantly reduced. ART significantly upregulated intracellular ROS level and promoted the formation of autophagosomes. NAC could reduce the inhibitory effect of ART on CFPAC-1 and Capan-2 cells， upregulate p-AMPK/AMPK， P62 and LC3Ⅱ/Ⅰ， downregulate the expression of p-mTOR/mTOR， and intensify autophagy. 3-MA could not reverse the inhibitory effect of ART on PC cells. 【Conclusion】 ART is dependent on ROS， but not on autophagy， in exerting an anti-pancreatic carcinoma effect. NAC attenuates the inhibitory effect of ART on PC cells by activating protective autophagy through AMPK/mTOR signaling pathway.
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Abstract@#The health of children and adolescents is not only related to the growth and wellbeing of individuals, but also to the construction and development of countries. This study reviewed policies that were issued by the central government since the founding of New China which focused on the prevention and treatment of common diseases among school-age children and adolescents. The results revealed that, since the founding of New China, policies for the prevention and control of common diseases among school-age children and adolescents increased in number, and they began to focus on specific rather than general health problems. A gradual emphasis was placed on the specific implementation of prevention and control measures, rather than on guiding principles. Increasingly more attention has been paid to the prevention and treatment of common diseases among school-age children and adolescents.
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Objective To explore the fitting and its influencing factors of ICU nurses. Methods There were 268 nurses recruited from the First Affiliated Hospital of Xi′an Jiaotong University, the Ninth Hospital of Xi′an, Shaanxi Provincial People′s Hospital by convenience sampling between April and June 2018. The Fitting Scale, Social Undermining Scale, Perceived Organizational Support Scale and Supportive Communication Scale were used in the investigation. Results The score of person-organization fit was (32.20±5.17). The score of person-job fit was (55.14±8.24), with the lowest score of supply-value fit subscale (2.58±0.48). The score of perceived organizational support, social undermining and supportive communication were (45.36 ± 9.64), (46.27 ± 7.48) and (68.47 ± 11.25) respectively. Perceived organizational support, social undermining, contract nurses, and educational level could influence person- organization fit, which could explain 59.3% of the total variation. Working time, supportive communication and perceived organizational support could influence person- job fit, which could explain 47.6% of the total variation. Conclusions Nursing managers should improve the core value system of human resources management and organizational culture construction, enhance organizational support, construct humanities environment and coping strategy of undermining, provide the relevant training of interpersonal communication, and increase their organizational and job fitting.
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Objective To explore the relocation stress in families of patients transferred from ICU, and the influence of social comparison orientation and family function on it. Methods There were 168 participants recruited from Critical Medical Department of the First Affiliated Hospital of Xi′an Jiaotong University by convenience sampling method between June 2017 and February 2018. The ICU patients′Family Relocation Stress Scale, Chinese version of the Iowa-Netherland Social Comparison Orientation Measure and Family Adaptation and Cohesion Evaluation Scale Ⅱ were used. Results The score of relocation stress and social comparison orientation were 58.47±7.66 and 37.83±9.11. The score of family real cohesion was 65.85 ± 7.83, which was higher than norms (t=-2.067, P<0.05). The score of dissatisfaction of adaptation was 9.22±4.41, which was higher than norms (t=-3.093, P<0.05). The results of regression analysis showed that the time of patient staying in ICU, education level, religion, social comparison orientation, family real cohesion and dissatisfaction of adaptation could influence relocation stress. Conclusion Health professionals should pay attention to the relocation stress in families, provide emotional support and effective information support, guide family members to correctly understand the patients′ condition and prognosis, respect their religious beliefs, give full play to their family functions, help them adapt to the role changes quickly and reduce the level of relocation stress.
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Objective@#To explore the fitting and its influencing factors of ICU nurses.@*Methods@#There were 268 nurses recruited from the First Affiliated Hospital of Xi′an Jiaotong University, the Ninth Hospital of Xi′an, Shaanxi Provincial People′s Hospital by convenience sampling between April and June 2018. The Fitting Scale, Social Undermining Scale, Perceived Organizational Support Scale and Supportive Communication Scale were used in the investigation.@*Results@#The score of person-organization fit was (32.20±5.17). The score of person-job fit was (55.14±8.24), with the lowest score of supply-value fit subscale (2.58±0.48). The score of perceived organizational support, social undermining and supportive communication were (45.36±9.64), (46.27±7.48) and (68.47±11.25) respectively. Perceived organizational support, social undermining, contract nurses, and educational level could influence person- organization fit, which could explain 59.3% of the total variation. Working time, supportive communication and perceived organizational support could influence person- job fit, which could explain 47.6% of the total variation.@*Conclusions@#Nursing managers should improve the core value system of human resources management and organizational culture construction, enhance organizational support, construct humanities environment and coping strategy of undermining, provide the relevant training of interpersonal communication, and increase their organizational and job fitting.
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Objective To explore the dynamic change and relationship between post-traumatic stress disorder (PTSD) and cognition in patients transferred from ICU. Methods Participants patients were selected from Critical Medical Department of the First Affiliated Hospital of Xi'an Jiaotong University by convenience sampling method between October 2016 to February 2017. The Montreal Cognitive Assessment (MoCA) and the PTSD Cheeklist-Vivilian Version (PCL-C) were used to collect data at 3 days, 3 months and 6 months after transferring from ICU. Results The incidence of cognitive disorder at 3 time points were 29.4％(30/102), 20.0％(18/90), 17.8％(13/73)respectively, and MoCA scores was 25.83 ± 6.29,28.57 ± 5.43,28.86 ± 5.11, the difference was significant (F=6.204,P<0.01). The incidence of PTSD symptoms were 42.2％(43/102), 23.3％(21/90), 19.2％(14/73)respectively, and PCL-C scores was 35.24 ± 5.94, 28.68 ± 5.13, 26.92 ± 4.85, the difference was significant (F=10.125,P<0.01). There were significant relationship between cognition and PTSD level (r =0.299-0.543,P <0.05). The PTSD level in cognitive disorder patients was 37.52 ± 5.88, 31.15 ± 5.12, 29.84 ± 4.82, and that in non-cognitive disorder patients was 34.32 ± 5.76, 27.68 ± 4.91, 25.74 ± 4.59 the difference was significant (t =2.117, 2.651, 3.334,P<0.05). Conclusions Health workers should pay attention to the mental status and cognitive impairment of patients transferred from ICU, implement psychological and cognitive interventions early, which could improve the cognitive status and PTSD progression of patients, and improve their quality of life.
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Objective To investigate the effects of gestrinone on growth and apoptosis, as well as the expression of phosphatase and tension homologue deleted on chromosome 10(PTEN) in isolated ectopic endometrium cells in vitro and the underlying mechanisms. Methods Ectopic endometrium cells were cultured and exposed to gestrinone of different doses of 0, 10 -6 and 10 -4 mol/L respectively. The inhibition of the cells during 48 hours was determined by methylthiazolyl tetrazolium (MTT) assay, and the cell growth curve was made. Gestrinone was administered to the cells and at 24 hours the morphological changes were observed by transmission electron microscopy and the apoptosis rate, cell cycle and PTEN expression were monitored by flow cytometry (FCM) at the same time. Results Gestrinone at different concentrations could inhibit the growth and proliferation of ectopic endometrium cells in a dose- and time-dependent manner. The inhibition rate of cell growth after exposed to gestrinone for 8,16,24,32,40 and 48 h was 99.6%,87.3%,79.8%,62.3%,51.7% and 44.2% in the 10 -6 mol/L group,and 99.2%,77.1%,69.6%,51.1%,33.7% and 23.6% in the 10 -4 mol/L group (P
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Objective To investigate the role of tumor suppressor gene PTEN(phosphatase and tension homologue deleted on chromosome 10,PTEN)in apoptosis of ectopic endometrial cells induced by gestrinone. Methods Ectopic endometrium cells obtained from endometriosis were cultured and exposed to gestrinone in different concentrations. The inhibition of the cells during 48 hours was determined by MTT assay, and the cell growth curve was plotted. Then the morphological changes in cells treated with gestrinone for 24h were observed with transmission electron microscope, and the apoptosis rate, cell cycle of the cells and PTEN expression were assessed with flow cytometry analysis (FCM) at the same time. Results Gestrinone in different concentrations could inhibit the growth and proliferation of ectopic endometrium cells in a does and time dependent manner, and the cell growth curve was changed accordingly. After 24 hours exposure to gestrinone in the concentrations of 10 -6 to10 -4 mol/L, some apoptotic changes were observed in the cells under transmission electron microscope. FCM showed that after the exposure to gestrinone, the apoptotic rate of ectopic endometrial cells was 1.3% in 10 6 mol/L group and 15.0% in 10 -4 mol/L group, indicating that there was significantly increase in apoptosis when compared with the control group. At the same time the level of PTEN expression was also increased. Conclusion Gestrinone can significantly inhibit the growth and proliferation of ectopic endometrial cells in endometriosis, and this effects seems to be related to an increase in PTEN expression.
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Objective To investigate the effects of exposure of gravid rats to the persistent organic pollutants (POPs), methoxychlor (MXC), on the placenta and their progeny during gestation periods. Methods According to different dosage levels of MXC [16, 32, 64 and 0 mg/(kg?d)], forty female SD rats aged 3-month were randomly divided into low-dosage group, mid-dosage group, high-dosage group and control group, with 10 animals for each. All the rats received intraperitoneal injection of MXC for 20 days. The influence of MXC on placenta of gravid rats and their progeny were observed in all aspects. Results With the increase in MXC dosage, intense changes were found in the rats, including an inerease in the number of corpus luteum of ovary, the number of nidation, fetal death and merging fetal (P