ObjectiveTo investigate the effect of diammonium glycyrrhizinate (DG) plus bone marrow mesenchymal stem cells (MSCs) transplantation in the treatment of acute exacerbation of pulmonary fibrosis induced by bleomycin (BLM) in rats.MethodsMSCs were isolated from male Wistar rats and cultured in vitro. Twenty-four female Wistar rats were randomly divided into 4 groups. The NC group was intratracheally injected with normal saline; the BLM group, the MSC group and the DGMSC group were intratracheally injected with BLM for 7 days; then the MSC group was injected with 0.5 mL of MSCs solution (2.5×106 cells) into the tail vein; the DGMSC group was intraperitoneally injected with DG for 21 days in a dose of 150 mg·kg–1·d–1 on the base of the MSCs injection. The rats were sacrificed on the 28th day and the lung tissue was extracted. Pathological examination was performed to determine the degree of alveolitis and pulmonary fibrosis. Immunofluorescence was used to detect the number and distribution of alveolar type Ⅱ epithelial cells. Alkali hydrolysis method was used to determine the content of hydroxyproline (HYP) in lung tissue; thiobarbituric acid method was used to measure the content of malondialdehyde (MDA) in lung tissue; colorimetric method was used to determine the superoxide dismutase activity (SOD) and total antioxidant capacity (T-AOC); enzyme linked immunosorbent assay was used to detect the expression levels of tumor necrosis factor-α (TNF-α ) and transforming growth factor-β1 (TGF-β1) in lung tissue homogenates.ResultsThe DG combined with MSCs injection can reduce the degree of alveolitis and pulmonary fibrosis in BLM model rats. The content of HYP and TGF-β1 in lung tissue homogenate of the DGMSC group were significantly lower than those in the MSC group (P<0.05). Meanwhile, DG combined with MSCs injection significantly increased the antioxidant capacity of the BLM model rats. MDA content decreased, SOD activity and T-AOC ability improved significantly in the DGMSC group compared with the MSC group (P<0.05). The alveolar type Ⅱ epithelial cells were significantly increased and the cell morphology was maintained in the DGMSC group compared with the MSC group.ConclusionsDG has a synergistic effect with MSCs in treatment of acute exacerbation of pulmonary fibrosis. The mechanism may be related to reducing inflammatory factors during pulmonary fibrosis, attenuating oxidative stress and promoting MSCs migration into lung tissue and transformation to alveolar type Ⅱ epithelial cells.
Objective To investigated the early risk factors of AIDS severe pneumonia complicated with acute respiratory distress syndrome in order to carry out early recognition and intervention of ARDS and improve the prognosis of patients. Methods The clinical data of 232 patients with severe AIDS pneumonia admitted to Chengdu Public Health Clinical Medical Center from January 2017 to December 2020 were retrospectively analyzed, including general data, vital signs, laboratory examination indexes, basic diseases, etc. Firstly influential indexes for complicated with ARDS were screened by single factor logistic regression analysis, then the multicollinearity assessment indicators were filtered out in multi-factor logistic stepwise regression analysis, finally the receiver operating characteristic (ROC) curves were drawn and the predictive value of the indicators were assessed. Results Thirty-three of 232 AIDS patients with severe pneumonia were complicated with ARDS. The mortality rate in ARDS group was 81.8%. The intra-group mortality of non-ARDS group was 33.7%. Single factor logistic regression analysis showed that pH, acute physiology and chronic health evaluation Ⅱ grade, sequential organ failure assessment grade, white blood cell count, lactate dehydrogenase, α-hydroxybutyric acid dehydrogenase (α-HBDH), alanine aminotransferase (ALT), aspartic acid aminotransferase (AST), calcium, fibrinogen degradation produc (FDP) and D-dimer, total 11 indicators were associated with the incidence of ARDS. The multicollinearity analysis of the 11 indicators showed that there was no multicollinearity problem among the other 9 indicators except the variance inflation factor of ALT and AST which was greater than 10. Multivariate logistic stepwise regression analysis showed α-HBDH (OR=1.001, 95% confidence interval 1.000 - 1.002, P=0.045) and D-dimer (OR=1.044, 95% confidence interval 1.006 - 1.083, P=0.024) were independent factors. ROC curve indicated the following: alpha hydroxy butyric acid dehydrogenase (the area under ROC curve=0.667, P=0.002, the optimal threshold was 391 U/L, the corresponding sensitivity and specificity was 78.8% and 61.8%, respectively), D-dimer (the area under ROC curve=0.602, P=0.062, the optimal threshold was 4.855 μg/mL, the corresponding sensitivity and specificity was 42.4% and 82.9%, respectively). Conclusion AIDS severe pneumonia complicated with ARDS is associated with many factors, among whichα-HBDH (≥391 U/L) and D-dimer (≥ 4.855 μg/mL) on admission are independent risk factors, which have great early predictive value and can provide reference for early clinical identification of ARDS high-risk patients.
Post-traumatic stress disorder (PTSD) presents with complex and diverse clinical manifestations, making accurate and objective diagnosis challenging when relying solely on clinical assessments. Therefore, there is an urgent need to develop reliable and objective auxiliary diagnostic models to provide effective diagnosis for PTSD patients. Currently, the application of graph neural networks for representing PTSD is limited by the expressiveness of existing models, which does not yield optimal classification results. To address this, we proposed a multi-graph multi-kernel graph convolutional network (MK-GCN) model for classifying PTSD data. First, we constructed functional connectivity matrices at different scales for the same subjects using different atlases, followed by employing the k-nearest neighbors algorithm to build the graphs. Second, we introduced the MK-GCN methodology to enhance the feature extraction capability of brain structures at different scales for the same subjects. Finally, we classified the extracted features from multiple scales and utilized graph class activation mapping to identify the top 10 brain regions contributing to classification. Experimental results on seismic-induced PTSD data demonstrated that our model achieved an accuracy of 84.75%, a specificity of 84.02%, and an AUC of 85% in the classification task distinguishing between PTSD patients and non-affected subjects. The findings provide robust evidence for the auxiliary diagnosis of PTSD following earthquakes and hold promise for reliably identifying specific brain regions in other PTSD diagnostic contexts, offering valuable references for clinicians.
This study aims to investigate the role of calreticulin in (CRT) pressure overload induced cardiac hypertrophy. In our study, cardiac hypertrophy was induced by left ventricular pressure overload in male SD rats subjected to transverse aortic constriction (TAC) operation. Expression of gene and protein of calreticulin, markers of cardiac hypertrophy and endoplasmic reticulum stress (ERS) were measured with real-time qPCR and Western blot respectively. Meanwhile, atorvastatin (a known ERS inhibitor) and calreticulin-specific small interference ribonucleic acid (siRNA) were used to inhibit the expression of ERS and calreticulin respectively. The experimental data demonstrated that the gene and protein levels of calreticulin, hypertrophic and ERS markers were increased significantly in the heart tissues of TAC rat models after 4 weeks. Moreover, atorvastatin administration improved the cardiac function and reduced the expression of calreticulin and ERS markers in TAC rats. In addition, cultured primary neonatal rat cardiomyocytes (NCMs) were treated with norepinephrine (NE), angiotensionⅡ (AngⅡ) or isoprenaline (ISO) to induce hypertrophic phenotype and ERS. The expression of hypertrophic markers was reduced in NCMs transfected with calreticulin-siRNA. The results suggested that calreticulin might be a promising target for the treatment of cardiac hypertrophy.
Objective To investigate whether cigarette smoke promote endoplasmic reticulum associated apoptosis gene Caspase-12 expression. Methods Forty adult male Wistar rats were randomly divided into four groups, ie. group A ( control group) , group B ( exposed to cigarette smoke for two months) ,group C ( exposed to cigarette smoke for four months) , and group D ( exposed to cigarette smoke for four months, then quit smoking for one month) . The COPD rat model was established with passive smoking.Percentage of forced expiratory volume in first 0. 3 second to forced vital capacity ( FEV0. 3 /FVC) and peak expiratory flow ( PEF) were measured. Reverse transcriptase-polymerase chain reaction ( RT-PCR) was used to determine the mRNA expression of Caspase-12. Immunohistochemistry and Western blot were used todetermine the protein expression of Caspase-12. Caspase-12-fluorometric-assay-kit was used to determine Caspase-12 activity. Results The pulmonary function decreased ( P lt; 0. 05) and the lung structure was damaged in the group B compared with the group A. The lung function markedly decreased( P lt; 0. 05) andthe lung structure was obviously damaged in the group C compared with the group B. The pulmonary function had minor improvement( P gt; 0. 05) , and the lung structure injury was also significant in the group D in contrast with the group C. The expression and activity of Caspase-12 were remarkably increased in the group B compared with the group A( P lt; 0. 05) , elevated significantly in the group C compared with the group B ( P lt; 0. 05) , decreased slightly in the group D compared with the group C ( P gt; 0. 05 ) . Conclusion Cigarette smoke promotes the development of COPD by inducing the endoplasmic reticulum associated apoptosis gene Caspase-12 expression.
Objective To investigate the status and influencing factors of psychosis-related post-traumatic stress disorder (PR-PTSD) in hospitalized patients with schizophrenia. Methods A questionnaire survey was conducted among the hospitalized patients with schizophrenia in three grade Ⅱ or above psychiatric hospitals in Chengdu between March and July, 2022, using the convenient sampling method. Questionnaires included the General Information Questionnaire, Impact of Event Scale-revised (IES-R), Self-rating Depression Scales, Simplified Coping Style Questionnaire, and Intolerance of Uncertainty Scale. If the score showed skewed distribution, it was expressed by the median (lower quartile, upper quartile). According to IES-R score, the patients included were divided into 2 groups. The patients whose score ≥33 were divided into PR-PTSD group, and <33 were divided into non-PR-PTSD group. The general information of the two groups of patients were compared. The correlation between PR-PTSD and depression, coping style and intolerance of uncertainty of the included patients were analyzed. The factors affecting the PR-PTSD of hospitalized patients with schizophrenia were analyzed by multivariate binary logistic regression analysis. Results A total of 388 patients were included. Among them, there were 282 cases in the non-PR-PTSD group and 106 cases in the PR-PTSD group. The IES-R score was 23.00 (15.00, 33.00), the depression score was 45.00 (38.00, 53.00), the negative coping style score was 11.00 (8.00, 14.75), the positive coping style score was 20.00 (16.00, 25.00), and the intolerance of uncertainty score was 28.00 (22.25, 33.00). IES-R was positively correlated with depression (r=0.370, P<0.001), negative coping style (r=0.396, P<0.001), positive coping style (r=0.111, P=0.029) and intolerance of uncertainty (r=0.467, P<0.001). Regression analysis showed that depression [(odds ratio, OR)=1.073, 95% confidence interval (CI) (1.043, 1.105), P<0.001)], negative coping style [OR=1.121, 95%CI (1.040, 1.208), P=0.003], intolerance of uncertainty [OR=1.081, 95%CI (1.045, 1.118), P<0.001] were the influencing factors of PR-PTSD in hospitalized patients with schizophrenia. Conclusions The prevalence of PR-PTSD in hospitalized patients with schizophrenia is high. Depression, negative coping style and intolerance of uncertainty are the risk factors for PR-PTSD in hospitalized schizophrenia patients.
ObjectiveTo investigate effects of high expression of miR-499a-5p on lung injury in rats with acute respiratory distress syndrome (ARDS) by targeting matrix metallopeptidase-16 (MMP-16).MethodsThe experiment set up sham operation group, model group, miR-499a-5p mimic group, MMP-16 group, miR-499a-5p mimic+MMP-16 group, D-ribofuranosylbenzimidazole (DRB, Nrf2 signaling pathway inhibitor) group, miR-499a-5p mimic+DRB group. A rat model of ARDS was constructed by cecal puncture. One hour before surgery, the transfection complex (50 μL) was injected into the trachea with a micro-syringe. DRB (5 mg/kg) was intraperitoneally injected 30 min before surgery. The expression levels of miR-499a-5p and MMP-16 in lung tissue were detected by RT-qPCR; Alveolar type Ⅱ epithelial cells of model group rats were separated and MMP-16 3 'UTR WT and MUT luciferase report plasmid were transfected into alveolar type Ⅱ epithelial cells with miR-499 respectively to verify the targeting relationship between miR-499 and MMP-16; the targeted relationship was verified by the dual luciferase reporter gene; lung injury was observed by hematoxylin-eosin staining; The level of inflammatory factors in bronchoalveolar lavage fluid (BALF) and the level of oxidative stress in lung tissue were detected by enzyme-linked immunosorbent assay; The expression levels of NAD(P)H: quinone oxidoreductase 1 (NQO1), heme oxygenase (HO)-1, and nuclear factor-erythroid 2-related factor 2 (Nrf2) proteins in lung tissues were analyzed by Western blotting.ResultsmiR-499a-5p was down-regulated in the lungs of ARDS model rats (P<0.01), while MMP-16 was highly expressed (P<0.01); miR-499a-5p and MMP-16 3'UTR regions had binding sites, and miR-499a-5p directly targeted negative regulation of MMP-16 expression (P<0.01); overexpression of miR-499a-5p significantly reduced the right lung wet-to-dry weight ratio in the ARDS rats (P<0.05), reduced lung tissue damage (P<0.01), and reduced tumor necrosis factor α, interleukin (IL)-1β and IL-6 levels in BALF (P<0.01), decreased malondialdehyde and myeloperoxidase levels in lung tissue, increased total anti-oxidant capacity (P<0.01), and up-regulated NQO1, HO-1, Nrf2 protein expression in lung tissue (P<0.01). However, this phenomenon was significantly reversed after the addition of MMP-16 and DRB.ConclusionOverexpression of miR-499a-5p attenuates lung injury in rats with ARDS by targeting negative regulation of MMP-16 via activating the Nrf2 signaling pathway.
Post-traumatic stress disorder (PTSD) is a mental disorder causing great distress to individuals, families and even society, and there is not yet effective way of unified prevention and treatment up till now. Lots of neuroimaging techniques, however, such as the magnetic resonance imaging, are widely used to the study of the pathogenesis of PTSD with the development of medical imaging. Functional magnetic resonance imaging (fMRI) can be applied to detect the abnormalities not only of the brain morphology but also of the function of various cerebral areas and neural circuit, and plays an important role in studying the pathogenesis of psychiatric diseases. In this paper, we mainly review the task-related and resting-state functional magnetic resonance imaging studies of the PTSD, and finally suggest possible directions for future research.
Metabolic memory means if the hyperglycemia can't be controlled at early stage of diabetes, chronic complications such as diabetic retinopathy (DR) will continue to develop even if the blood glucose level maintains normal level at later stage. Oxidative stress plays an important role in the "metabolic memory" of DR, which interacts with the nitrative stress, advanced glycation end products, genetic modification and endoplasmic reticulum stress in the pathogenesis of DR. Further elucidation of the relationship between oxidative stress and "metabolic memory" of DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
Objective To study the effect and mechanism of recombinant human brain natriuretic peptide (rh-BNP) in alleviating myocardial ischemia-reperfusion (I/R) injury by regulating mitogen activated protein kinase (MAPK) pathway. Methods A total of 128 adult male Sprague-Dawley (SD) rats with specific pathogen free were selected. The SD rats were divided into groups according to random number table, including, sham operation (Sham) group, I/R group, I/R+rh-BNP group, negative control adenovirus (Ad-NC)+Sham group, Ad-NC+I/R group, Ad-NC+I/R+rh-BNP group, p38 mitogen-activated protein kinase adenovirus (Ad-p38MAPK)+I/R group and Ad-p38MAPK+I/R+rh-BNP group, with 16 SD rats in each group. Myocardial I/R injury model was established by ligation of left anterior descending coronary artery. Before modeling, rh-BNP was injected intraperitoneally or adenovirus was injected into myocardium; 180 minutes after reperfusion, the contents of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) in serum, myocardial infarction size, the contents of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and the expression of phosphorylated p38MAPK (p-p38MAPK), phosphorylated JNK (p-JNK) and phosphorylated extracellular regulated protein kinases 1/2 (p-ERK1/2) were detected. Results The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK and p-JNK in I/R group were higher than those in Sham group, p-ERK1/2 expression level was lower than that in Sham group (P<0.05). The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK in I/R+rh-BNP group were lower than those in I/R group (P<0.05), the expression of p-JNK and p-ERK1/2 had no significant difference compared with I/R group (P>0.05). The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK in Ad-p38mapk+I/R+rh-BNP group were higher than those in Ad-NC+I/R-rh-BNP group (P<0.05). Conclusion rh-BNP can alleviate myocardial I/R injury, which is related to inhibiting p38MAPK pathway, reducing inflammation response and oxidative stress response.