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Background The senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear. Objective To explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethods This study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO2 suspension (100 mg·mL−1). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L−1 and 1125 mmol·L−1). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO2. The in vitro experimental groups were ① SiO2 induction groups: control group, 50 μg·mL−1 SiO2 group, 100 μg·mL−1 SiO2 group, and 200 μg·mL−1 SiO2 group, and ② oxamate treatment groups: control group, SiO2 group (100 μg·mL−1), low-dose oxamate (25 mmol·L−1) treatment group, and high-dose oxamate (50 mmol·L−1) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting. Results Compared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO2-induced MLE-12 cells (P<0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P<0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P<0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO2-induced group (P<0.05). Compared with the SiO2 group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P<0.05). Conclusion Lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.
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Background Pneumoconiosis is the most serious occupational disease in China, and silicosis accounts for about half of it. Any intervention effect of physical exercise as the key and core of lung rehabilitation training on silicosis is still unclear. Objective To explore potential intervention effect of physical exercise on silicotic mice. Methods Forty SPF C57BL/6 male mice were randomly divided into four groups, 10 in each group, including a control group, a physical exercise group, a silicosis model group, and a silicosis model + physical exercise intervention group. Silicotic mouse model was established by using 50 μL SiO2 suspension (200 mg·mL−1). A treadmill was used to prepare mice receiving physical exercise at 0° inclination, 12.3 m·min−1, 60 min·d−1, 5 d·week−1 for 4 weeks. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after Van Gieson (VG) staining; expression of p-protein kinase R-like endoplasmic reticulum kinase (PERK) was detected by immunofluorescence staining; expressions of cyclin dependent kinase inhibitors (p21) and p-p38 mitogen activated protein kinase (p38) were detected by immunohistochemistry. The protein expressions of endoplasmic reticulum stress signal factors [p-inositol-requiring enzyme-1α (p-IRE-1α), p-PERK, and p-eukaryotic initiation factor-2α (p-eIF-2α)], senescence signal factors (p-p53, p21, and p16), mitogen-activated protein kinase (MAPK) signal factors [p-p38, p-extracellular regulated protein kinases (p-ERK), and p-stress-activated protein kinase (p-JNK)] were detected by Western blotting. Results After designed acute SiO2 exposure, the images of micro computed tomography (CT) showed high density shadows in lung tissues of the silicotic mice and less shadows in lung tissues of the physical exercise intervention mice. After HE staining, the proportions of silicotic nodule area in lung tissues was (18.67±3.89) % in the silicosis model group, and significantly decreased to (8.78±1.05) % in the silicosis model + physical exercise intervention group (P<0.05). After VG staining, the proportion of collagen fiber area of lung tissues was (10.37±2.18) % in the silicosis model group, and significantly decreased to (4.35±0.89) % in the silicosis model + physical exercise intervention group (P<0.05). The results of immunofluorescence staining showed that in the silicosis model group, the expression of p-PERK increased at the location of silicotic nodules, while in the silicotic model + physical exercise intervention group, the expression of p-PERK decreased. The immunohistochemical staining results showed that the expression of p21 and p-p38 increased in the lung tissues of the silicosis model group; the expression of p21 and p-p38 decreased in the lung tissues of the silicosis model + physical exercise intervention group. The results of Western blotting showed that compared with the control group, the expression levels of p-IRE-1α (0.11±0.03), p-PERK (0.95±0.40), p-eIF-2α (3.53±0.91), p-p53 (1.78±0.07), p21 (1.98±0.10), p16 (1.26±0.17), p-p38 (0.41±0.09), p-ERK (0.42±0.05), and p-JNK (3.20±1.23) of the silicosis model group were all upregulated (P<0.05). Compared with the silicosis model group, the expression levels of p-IRE-1α (0.03±0.01), p-PERK (0.31±0.12), p-eIF-2α (0.30±0.06), p-p53 (0.76±0.08), p21 (0.18±0.11), p16 (0.70±0.24), p-p38 (0.03±0.00), p-ERK (0.19±0.03), and p-JNK (0.46±0.21) of the silicosis model + physical exercise intervention group were downregulated (P<0.05). Conclusion Physical exercise may alleviate pulmonary fibrosis in silicotic mice, and inhibit abnormal expressions of endoplasmic reticulum stress signal, MAPK signal, and senescent signal.
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OBJECTIVE@#To detect the expression level of HK2 gene in the bone marrow of newly diagnosed patients with acute myeloid leukemia (AML) and investigate its influence on the clinical characteristics and prognosis.@*METHODS@#The expression level of HK2 gene in the bone marrow of 90 newly diagnosed patients with AML that accompanying clinical characteristics and survival status were detected by RT-qPCR, and compared with 18 allogeneic hematopoietic stem cell transplantation (allo-HSCT) donors. The Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards regression model were used to analyze the correlation of HK2 expression level with clinical characteristics and prognosis.@*RESULTS@#Compared with allo-HSCT donors, the HK2 expression was significantly increased in newly diagnosed AML patients (P <0.01). Compared with patients with total response (OR, complete response + complete response with incomplete hematologic recovery) after 2 courses of induction chemotherapy, the expression of HK2 in patients without OR was significantly increased (P <0.05). There was a significant difference in the relative expression of HK2 between patients with and without OR after 2 courses of induction therapy (P <0.001). The median survival time of patients with high expression of HK2 was significantly shorter than that of patients with low expression of HK2 (P <0.05). The multivariate Cox proportional hazards regression analysis showed that prognostic stratification, the expression level of HK2, and whether two courses of induction therapy achieved OR were independent factors affecting the prognosis of AML patients (P <0.05).@*CONCLUSIONS@#Compared with allo-HSCT donors, the expression level of HK2 gene is increased in the bone marrow of newly diagnosed AML patients. The prognosis of patients with high expression of HK2 is poor. The expression level of HK2 is an independent factor affecting the prognosis of AML patients.
Subject(s)
Humans , Bone Marrow , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/therapy , Prognosis , Retrospective Studies , Transplantation, Homologous/adverse effectsABSTRACT
Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.
Subject(s)
Animals , Ear, Inner/growth & development , Embryo, Nonmammalian/drug effects , Gene Expression Regulation, Developmental/drug effects , Hair Cells, Auditory/metabolism , Lateral Line System/growth & development , Locomotion/drug effects , Ototoxicity/physiopathology , Toluene/toxicity , ZebrafishABSTRACT
OBJECTIVE@#To test the reliability and validity of the Chinese version of parenting sense of competence scale (PSOC) in Chinese mothers of preschool children, and to explore the perception of preschool children's mothers on their own parenting skills and their comfort of being a parent in Yanqing District of Beijing.@*METHODS@#A cross-sectional survey was conducted using a convenience sample in 1 384 preschool children's mothers in Yanqing District of Beijing. SPSS 21.0 and Mplus 7.4 software were used for statistical analysis to test the structural validity, criterion related validity, internal consistency and split half reliability of the scale, and to analyze the score of the scale and its influencing factors.@*RESULTS@#The PSOC had good reliability and validity. Exploratory factor analysis showed that each item of the PSOC had more than 0.4 factor loading in efficacy factor or satisfaction factor, and there was no double load phenomenon. Confirmatory factor analysis showed that the factor loadings ranged from 0.212 to 0.843 in efficacy factor and satisfaction factor, respectively. The goodness of fit test showed that all the fitting indexes were within the acceptable range, and the correlation between the effectiveness subscale and the satisfaction subscale was high. The Cronbach's α coefficient of the whole scale, the efficacy subscale and the satisfaction subscale were 0.872, 0.802, and 0.874, respectively. The Spearman-Brown coefficient of PSOC was 0.851. The average score of the whole scale, the efficacy subscale, and the satisfaction subscale were 72.33±11.31, 35.54±5.91, and 36.79±7.11, respectively, and the score of parenting competence in Chinese mothers of preschool children was influenced by the mother's educational level and the annual income of her family.@*CONCLUSION@#The PSOC has satisfactory reliability and validity in Chinese mothers of preschool children. It can be used as an evaluation instrument for measuring the parenting competency, self perceived efficacy and satisfaction in the mainland Chinese mothers of preschool children. The competency of preschool children's mothers in Yanqing District of Beijing is very good, which may be related to the higher education level of the mothers and the higher annual income of their families in this study.
Subject(s)
Child, Preschool , Female , Humans , Beijing , China , Cross-Sectional Studies , Mothers , Parenting , Psychometrics , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
OBJECTIVE@#To analyze and investigate the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with T cell acute lymphoblastic leukemia (T-ALL) and their significance.@*METHODS@#Sixty patients with T-ALL and 60 patients with acute myelogenous leukemia (AML) diagnosed in our hospital from June 2012 to March 2015 were enrolled in T-ALL group and AML group, respectively. Another 30 healthy people were enrolled in the control group. Peripheral blood was collected to detect the expression levels of HES1, C-MYC and NF-kB by RT-PCR. The general data and the expression of HES1, C-MYC and NF-kB in peripheral blood were compared among the patients with different type of leukemia, cytogenetical types and different prognosis.@*RESULTS@#There was no significant difference in baseline data, such as age and sex among the 3 groups (P>0.05). The Hb level, WBC and Plt count, BM blast cell ratio in T-ALL and AML groups all were significantly higher than those in control group (P<0.01), but there were no statistical difference in above-mentioned indicators between T-ALL and AML groups (P>0.05). The expression levels of HES1, C-MYC and NF-kB in peripheral blood among 3 groups were significantly differenct (P<0.01), the expressions levels of HES1, C-MYC and NF-kB in T-ALL and AML groups were significantly higher than those in control were significantly group (P<0.01), moreover, the expression levels of above-mentional indicators in T-ALL groups were significantly higher than than those in AML group (P<0.01). The expression levels of HES1, C-MYC and NF-kB iin T-ALL patients with poor prognosis were significantly higher than those in T-ALL patients with favorable prognosis (P<0.01); the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with different theraptic efficacy were follow: complete remission group<partial remission group<no remission group (P<0.01).@*CONCLUSION@#The HES1, C-MYC and NF-kB are highly expressed in peripheral blood of the patients with T-ALL, moreover, the expression levels maybe different, because of the cytogenetic, and theraptic efficacy.
Subject(s)
Humans , Leukemia, Myeloid, Acute , NF-kappa B , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Remission Induction , T-Lymphocytes , Transcription Factor HES-1ABSTRACT
OBJECTIVE: observe the changes of localization and expression of acetylated tubulin alpha( Ac-tubulin α) in fibroblasts of silicosis fibrosis. METHODS: i) A total of 22 autopsy case with coal workers' pneumoconiosis( CWP) was selected as CWP group( autopsy lesion lung tissue) and their adjacent normal lung tissues surrounding fibrotic regions were selected as the control group using typical sampling method. ii) Specific pathogens free healthy male rats were randomly divided into control group and 5 dust-exposed groups with 10 rats in each group. In dust-exposed group,the rats were exposed to 2 000 mg/m~3 of silica dust for 0,2,4,8,12 and 16 weeks respectively by dynamic inhalation. The rats in control group were given no treatment. iii) Primary cultured rat lung fibroblasts were induced by Ang Ⅱ at a concentration of 100 nmol/L at different time points( 0,5,15 and 30 min,1,3,6,12,24 and 48 hours). iv) The expression of Ac-tubulin α and α-smooth muscle actin( α-SMA) were detected by immunohistochemical staining. The expression of Ac-tubulinα/Vimentin and Ac-tubulin α/α-SMA were observed by immunofluorescence staining. The relative expression ofα-SMA and Ac-tubulin α protein was detected by Western blot. RESULTS: The positive expression of Ac-tubulin α in lung tissue of CWP group was down-regulated while that of α-SMA was up-regulated compared with the control group( P < 0. 01). Immunofluorescence results showed that Vimentin positive expression in the CWP group was significantly increased in the lesion fibrosis area,while Ac-tubulin α expression was absent. The co-expression of Ac-tubulin α and Vimentin was detected in normal lung tissue of control group. The animal experiment results showed that the expression of Ac-tubulin αin lung tissue of rats was down-regulated and that of α-SMA was up-regulated with the prolongation of dust exposure time( P < 0. 01). The Ang Ⅱ induced the differentiation of fibroblasts into myofibroblasts,and the expression of Ac-tubulin α in fibroblasts gradually decreased and the expression of α-SMA gradually increased with the prolongation of Ang Ⅱ induction time( P < 0. 05). CONCLUSION: The lack of expression of Ac-tubulin α may be involved in the occurrence and development of silicotic fibrosis.
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Background Endophthalmitis is a serious infectious eye disease.Efficient drug therapy plays a key role in the early stage.There have been few researches on teicoplanin treating endophthalmitis and pharmacokinetics in ocular tissue.Objective The present study was to investigate the intraocular pharmacokinetic course and feature of intravitreal administration of teicoplanin.Methods Thirty-three Japanese white rabbits were included in this study and randomized into 6 groups.The right eyes of the rabbits were used in experiment.5 g/L of teicoplanin was injected into the vitreous cavity,and vitreous and aqueous humor samples were extracted after 15 minutes,30 minutes,1,2,4,6,12,24,48,96 and 192 hours,and the concentration of teicoplanin was determined by bioassay.Results The logarithmic value of the concentration of teicoplanin was raised with the increase in the bacterial inhibition zone diameters,of which the equation of the regression curve was Y =0.174X-0.813(R2=0.999).A good linear relationship was presented within 1.0-80.0 mg/L.Single intravitreal injection of teicoplanin was compliant with the two-compartment model.Moreover,the distribution phase Tα1/2 and elimination phase Tβ1/2 of vitreous were 1.68 and 152.15 hours,separately.And Tα1/2 and Tβ1/2 of the aqueous humor were 2.83 hours and 70.56 hours,individually.The peak teicoplanin concentrations in the vitreous and aqueous humor were(358.47±21.53)mg/L and(102.17±9.54)mg/L at 1 hour,respectively and remained at(4.38±0.68)mg/L and(2.38±0.38)mg/L,respectively 192 hours later.Conclusions Intravitreal injection of 0.5 mg of teicoplanin can remain therapeutic concentration for a long time in the vitreous and aqueous humor.
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<p><b>OBJECTIVE</b>To evaluate the clinical outcome among three different laser in situ keratomileusis (LASIK) ablations: Q-factor customized ablation (aberration smart ablation, ASA), wave-front guided ablation (WASCA) and ablation under wave-front guiding plus iris recognition system (IR+WASCA).</p><p><b>METHODS</b>This prospective study comprised 96 eyes of 96 patients, and they were randomly divided into three groups: 30 patients in ASA group, 32 in WASCA group, and 34 in IR+WASCA group. There were no any statistical differences in spherical equivalent (SE), age, sex, pupil diameter, higher-order aberrations (HOA) among three groups preoperatively. Wave-front analysis was performed before and 1, 3 months after operation.</p><p><b>RESULT</b>All patients got an uncorrected visual acuity (UCVA) ≥ 0.8 1 and 3 months after operation. The residual SE was in ± 0.50D both at 1 and 3 months after surgery. There was no statistical difference in SE value, HOA, change of HOA, and coma aberration postoperatively among three groups. Horizontal coma (Z3¹) aberration took the majority of coma. HOA, total coma aberrations and spherical aberration increased postoperatively (P = 0.000), but without significant difference between 1 month and 3 months after surgery.</p><p><b>CONCLUSION</b>That three customized LASIK are all effective, safe, accurate and stable; meanwhile WASCA may have better UCVA than the other two groups postoperatively.</p>
Subject(s)
Humans , Follow-Up Studies , Keratomileusis, Laser In Situ , Methods , Myopia , General Surgery , Prospective Studies , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To identify and explore the prognostic risk factors of the hemophagocytic syndrome (HPS).</p><p><b>METHODS</b>A retrospective study was conducted on 50 childhood patients with HPS who were admitted to our hospital between 2007 and 2011. All their medical records were reviewed and analyzed. For each patient, demographic, laboratory data and outcome information were collected. The patients were divided into deceased or survived groups based on the follow-up results. Comparative analysis of the data was done by using independent-samples test and logistic multiple and univariate regression.</p><p><b>RESULTS</b>Among the 50 HPS patients, 30 were male and 20 female, age ranged from 3 months to 10 years. Reduction of serum albumin, cholinesterase and natural killer (NK) cells was found in the forty-six patients. The laboratory features showed an elevation of serum ferritin with hypofibrinogenemia and hypertriglyceridemia in most of the patients. Forty of patients had hemophagocyte in bone marrow at diagnosis of HPS. The positive serum EBV-IgM was found in thirty-five patients.During the observation period, 25 of 37 patients (67.6%) died, while 13 of whom died within a month after hospitalization. The deceased patients were more likely to have lower albumin, cholinesterase, NK cells level and more prolonged active partial thromboplastin time than the survived patients (P < 0.05). Multivariate logistic regression analysis revealed that duration of illness > 1 month, albumin level < 25 g/L, cholinesterase level < 2000 U/L, NK cell level 0-3% and positive EBV-IgM were related with the prognosis significantly (P < 0.05 for all comparisons).</p><p><b>CONCLUSION</b>This study revealed that duration of illness > 1 month, decreases in albumin, NK cell and cholinesterase, and positive EBV-IgM were the risk factors related to mortality in children.</p>