ObjectiveTo investigate the molecular pathogenesis of pulmonary fibrosis induced by bleomycin in a murine model,and provide novel insights for clinical diagnosis and treatment. MethodsFrom Gene Expression Omnibus,we downloaded microarray data extracted from experiments of bleomycin induced pulmonary fibrosis in wild-type mice. With BRB-Array Tools,differentially expressed genes at different time points during disease development were screened,selected and analyzed by DAVID software. ResultsBRB array analysis identified 45101 differentially expressed genes. After induction by bleomycin on 7th day,1164 genes and 735 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. On 14th day,731 genes and 390 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. DAVID analysis revealed that the up-regulated genes were significantly enriched in cell cycle,p53 signaling and chemokine signaling pathway,damaging reaction and collagen metabolism gene sets. While the down-regulated genes were enriched in the drug metabolism pathway gene set. ConclusionsBioinformatics methodologies are able to efficiently analyze microarray data and extract its underlying information,provide novel insights for major molecular events and shift of cell signaling pathway during pulmonary fibrosis progression,and furthermore,finding molecular markers for early diagnosis and therapeutic targets.
The dose data produced by treatment plan system (TPS) in intensity-modulated radiation therapy (IMRT) has many gradient edge points. Considering this feature we proposed a new interpolation algorithm called treatment plan dose interpolation algorithm based on gradient feature in intensity-modulated radiation therapy (TDAGI), which improves the Canny algorithm to detect the gradient edge points and non-edge points by using the gradient information in the dose data plane. For each gradient edge point, the corresponding gradient profile was traced and the profile's sharpness was calculated, and for each non-edge point, the dispersion was calculated. With the sharpness or dispersion, the kernel coefficients of bi-cubic interpolation can be obtained and can be used as the central point to complete the bi-cubic interpolation calculation. Compared with bi-cubic interpolation and bilinear interpolation, the TDAGI algorithm is more accurate. Furthermore, the TDAGI algorithm has the advantage of gradient keeping. Therefore, TDAGI can be used as an alternative method in the dose interpolation of TPS in IMRT.
ObjectiveTo investigate the clinical heterogeneity and auto-immunologic state in patients with diabetic ketosis (DK) or diabetic ketoacidosis (DKA). MethodsDiabetic patients who presented with DK/DKA were recruited from West China Hospital of Sichuan University from January 1, 2000, to December 31, 2008. We analyzed the clinical classification, biochemical profiles, and auto-immunologic state of the patients. ResultsAmong them, 257 (15.0%) patients had type 1 diabetes, while 883 (51.6%) with type 2 diabetes, and 515 (30.1%) could be typed as "atypical diabetes" or "untying diabetes". The average age of hospitalized patients with type 1 diabetes was (31.1±13.5) years, which was significantly lower than that of the type 2 diabetes patients [(58.1±13.2) years] (P<0.001). The most common contributing factor for DK/DKA was infection, followed by noncompliance with therapy. Glutamic acid decarboxylase antibody positive rate was 4.37% in patients with "atypical diabetes", which was similar with type 2 diabetes group (2.69%, P=0.79), but lower than that of the patients with type 1 diabetes (13.79%, P<0.001). ConclusionsWe conclude that DK or DKA can occur not only in type 1 diabetic patients but also in patients with type 2 diabetes under infection or stress condition. DK/DKA patients have a high clinical heterogeneity. The auto-immunologic state and β-cell function have significant implications for the diagnosis and classification of diabetes.
ObjectiveTo analyze the expression profile changes of osteogenic-related genes during spontaneous calcification of rat bone marrow mesenchymal stem cells (BMSCs). MethodsBMSCs were isolated from 3-day-old healthy Sprague Dawley rats;cells at the 4th generation were used to establish the spontaneous calcification model in vitro. Spontaneous calcification process was recorded by inverted phase contrast microscope observation and alizarin red staining after 7 and 14 days of culture. For gene microarray analysis, cell samples were collected at 0, 7, and 14 days after culture; the differentially expressed genes were analyzed by bioinformatics methods and validated by real-time quantitative PCR (RT-qPCR) assay. ResultsRat BMSCs calcified spontaneously in vitro. When cultured for 7 days, the cells began to aggregate and were weakly positive for alizarin red staining. After 14 days of culture, obvious cellular aggregation and typical mineralized nodules were observed, the mineralized nodules were brightly positive for alizarin red staining. A total of 576 gene probe-sets expressed differentially during spontaneous calcification, corresponding 378 rat genes. Among them, 359 gene probe-sets expressed differentially between at 0 and 7 days, while only 13 gene probe-sets expressed differentially between at 7 and 14 days. The 378 differentially expressed genes were divided into 6 modes according to their expression profiles. Moreover, according to their biological functions, differentially expressed genes related to bone cell biology could be classified into 7 major groups:angiogenesis, apoptosis, bone-related genes, cell cycle, development, cell communication, and signal pathways related to osteogenic differentiation. In cell cycle group, 12 down-regulated genes were linked with each other functionally. Matrix metalloproteinase 13 (Mmp13), secreted phosphoprotein 1 (Spp1), Cxcl12, Mmp2, Mmp3, Apoe, and Itga7 had more functional connections with other genes. The results of genes Spp1, Mgp, Mmp13, Wnt inhibitory factor 1, Cxcl12, and cyclin A2 by RT-qPCR were consistent with that of gene microarray. ConclusionThe first 7 days after rat BMSCs were seeded are a key phase determining the fate of spontaneous calcification. Multiple genes related with cell communication, bone-related genes, cell cycle, transforming growth factor-β signaling pathway, mitogen-activated protein kinase signaling pathway, and Wnt signaling pathway are involved during spontaneous calcification.
Objective To detect the bile acid profile in serum based on liquid chromatography-tandem mass spectrometry, and construct a combined biomarker diagnostic model for differentiating acute myocardial infarction (AMI) from unstable angina (UA). Methods A total of 180 patients with acute coronary syndrome who visited Huludao Central Hospital between August 2023 and February 2024 were randomly selected, and there were 117 patients with UA and 63 patients with AMI. Using liquid chromatography-tandem mass spectrometry, 15 bile acid subtypes in serum were detected. Orthogonal partial least squares discriminant analysis was used to compare the serum bile acid metabolic profiles of the subjects. Differences in metabolites were screened based on a significance level of P<0.05 and variable importance in projection (VIP)>1. Multiple logistic regression analysis was performed to construct a diagnostic model for differentiating AMI from UA, and the diagnostic performance of the model was evaluated using receiver operating characteristic (ROC) curve and other statistical methods. Results The differential bile acid biomarkers in the serum of UA and AMI patients included glycodeoxycholic acid, glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), glycocholic acid, and aurodeoxycholic acid (TDCA) (P<0.05, VIP>1). A binary logistic stepwise regression analysis showed that three bile acid biomarkers (GCDCA, DCA, and TDCA) and three common biochemical indicators (aspartate aminotransferase, creatine kinase, and total bile acid) were factors differentiating AMI from UA (P<0.05). The area under the ROC curve of the model was 0.986 [95% confidence interval (0.973, 0.999), P<0.001], demonstrating a good diagnostic performance. Conclusions GCDCA, DCA, and TDCA can serve as potential biomarkers for distinguishing AMI from UA. The model combining these three bile acids with aspartate aminotransferase, creatine kinase, and total bile acid can effectively identify AMI.
Objective To evaluate the safety and effectiveness of anterior cervical discectomy and fusion (ACDF) by using zero-profile anchored cage (ZAC) in treatment of consecutive three-level cervical spondylosis, by comparing with plate-cage construct (PCC). Methods A clinical data of 65 patients with cervical spondylosis admitted between January 2020 and December 2022 and met the selection criteria was retrospectively analyzed. During consecutive three-level ACDF, 35 patients were fixed with ZAC (ZAC group) and 30 patients with PCC (PCC group). There was no significant difference in baseline data between the two groups (P>0.05), including gender, age, body mass index, surgical segment, preoperative Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), visual analogue scale (VAS) score, prevertebral soft tissue thickness (PSTT), cervical lordosis, and surgical segmental angle. The operation time, intraoperative blood loss, hospital stay, clinical indicators (JOA score, NDI, VAS score), and radiological indicators (cervical lordosis, surgical segmental angle, implant subsidence, surgical segment fusion, and adjacent segment degeneration), and the postoperative complications [swelling of the neck (PSTT), dysphagia] were recorded and compared between the two groups. Results Patients in both groups were followed up 24-39 months. There was no significant difference in follow-up duration between the two groups (P>0.05). The operation time and intraoperative blood loss were lower in ZAC group than in PCC group, and the length of hospital stay was longer, but there was no significant difference (P>0.05). At each time point after operation, both groups showed significant improvements in JOA score, VAS score, and NDI compared with preoperative scores (P<0.05), but there was no significant difference between the two groups at each time point after operation (P>0.05). Both groups showed an increase in PSTT at 3 days and 3, 6 months after operation compared to preoperative levels (P<0.05), but returned to preoperative levels at last follow-up (P>0.05). The PSTT at 3 days and 3 months after operation were significantly lower in ZAC group than in PCC group (P<0.05), and there was no significant difference between the two groups at 6 months and at last follow-up (P>0.05). The incidences of dysphagia at 3 days and 3 months were significantly lower in ZAC group than in PCC group (P<0.05), while no significant difference was observed at 6 months and last follow-up between the two groups (P>0.05). There was no postoperative complication in both groups including hoarseness, esophageal injury, cough, or hematoma. Both groups showed improvement in cervical lordosis and surgical segmental angle compared to preoperative levels, with a trend of loss during follow-up. The cervical lordosis loss and surgical segmental angle loss were significantly more in the ZAC group than in PCC group (P<0.05). The incidence of implante subsidence was significantly higher in ZAC group than in PCC group (P<0.05). There was no significant difference between the ZAC group and PCC group in the incidences of surgical segment fusion and adjacent segment degeneration (P>0.05). ConclusionIn consecutive three-level ACDF, both ZAC and PCC can achieve satisfactory effectiveness. The former can reduce the incidence of postoperative dysphagia, while the latter can better maintain cervical curvature and reduce the incidence of implant subsidence.
ObjectiveTo evaluate the effectiveness of very low profile/variable angle locking plate (VLP) internal fixation for posterior Pilon fractures extending to the medial malleolus by posteromedial approach. MethodsA retrospective analysis was made on the clinical data from 13 patients with posterior Pilon fractures extending to the medial malleolus between December 2011 and August 2012. There were 4 males and 9 females with an average age of 48.9 years (range, 23-68 years). Fractures were caused by falling in 9 cases and by traffic accident in 4 cases. The locations were the left ankle in 6 cases and the right ankle in 7 cases. According to the Orthopedic Trauma Association (OTA) classification, 6 cases were rated as type 43B1, 4 cases as type 43B2, and 3 cases as type 43B3. Twelve cases had fibular fractures, including 11 cases of Denis-Weber type B, 1 case of Denis-Weber type C. The interval of injury and operation was 7-14 days (mean, 11.4 days). Open reduction was performed and VLP internal fixation was used for posterior malleolar fracture by posteromedial approach. ResultsPrimary healing of incision was obtained in all patients. Tibial nerve palsy was observed in 2 cases, and was cured after oral administration of mecobalamin. Twelve cases were followed up 12-18 months (mean, 14.5 months). According to the Burwell-Charnley's radiological evaluation system, 11 cases achieved anatomical reduction, 1 case achieved fair reduction. The fracture union time was 3-6 months (mean, 3.7 months). No loosening or breakage of internal fixation occurred during follow-up. According to the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, the results were excellent in 7 cases, good in 4, and fair in 1; the excellent and good rate was 91.7%. ConclusionVLP internal fixation for posterior Pilon fractures extending to the medial malleolus by posteromedial approach can achieve good short-term effectiveness. The high quality of reduction is acquired under direct vision with low rate of soft tissue complications.
The impeller profile, which is one of the most important factors, determines the creation of shear stress which leads to blood hemolysis in the internal flow of centrifugal blood pump. The investigation of the internal flow field in centrifugal blood pump and the estimation of the hemolysis within different impeller profiles will provide information to improve the performance of centrifugal blood pump. The SST κ-ω with low Reynolds correction was used in our laboratory to study the internal flow fields for four kinds of impellers of centrifugal blood pump. The flow fields included distributions of pressure field, velocity field and shear stress field. In addition, a fast numerical hemolysis approximation was adopted to calculate the normalized index of hemolysis (NIH). The results indicated that the pressure field distribution in all kinds of blood pump were reasonable, but for the log spiral impeller pump, the vortex and backflow were much lower than those of the other pumps, and the high shear stress zone was just about 0.004%, and the NIH was 0.0089.
There is a shared problem in current optical imaging technologies of how to obtain the optical parameters of biological tissues with complex profiles. In this work, an imaging system for obtaining the optical parameters of biological tissues with complex profile was presented. Firstly, Fourier transformation profilometry was used for obtaining the profile information of biological tissues, and then the difference of incident light intensity at different positions on biological tissue surface was corrected with the laws of illumination, and lastly the optical parameters of biological tissues were achieved with the spatial frequency domain imaging technique. Experimental results indicated the proposed imaging system could obtain the profile information and the optical parameters of biological tissues accurately and quickly. For the slab phantoms with height variation less than 30 mm and angle variation less than 40o, the maximum relative errors of the profile uncorrected optical parameters were 46.27% and 72.18%, while the maximum relative errors of the profile corrected optical parameters were 6.89% and 10.26%. Imaging experiments of a face-like phantom and a human’s prefrontal lobe were performed respectively, which demonstrated the proposed imaging system possesses clinical application value for the achievement of the optical parameters of biological tissues with complex profiles. Besides, the proposed profile corrected method can be used to combine with the current optical imaging technologies to reduce the influence of the profile information of biological tissues on imaging quality.
Objective To analyze the changes of gene expression profiles during the process that human bonemarrow mesenchymal stem cells (hBMSCs) are induced to differentiate into cardiomyogenic cells with 5-azacytidine (5-aza). Methods hBMSCs were isolated from marrow of obsolete ribs and induced with 5-aza. Then immunocytochemicalstaining was used to detect the expressions of α-actin, cardiac troponin T (cTnT), and connexin 43, and the percentage ofcTnT positive cells was tested with flow cytometry. In the process of differentiation, variation of gene expression was screenedwith Genechi ps Operating System of human gene expression profiles. And the differentially expressed genes were functionallyanalyzed and hierarchical clustered. Results When BMSCs were induced in vitro with 5-aza, part of the cells turnedinto myogenic cells morphologically. Before induction, immunocytochemical staining for α-actin and cTnT showed sl ightpositive and for connexin 43 showed negative. While after 3 weeks of induction, immunocytochemical staining for α-actin,cTnT, and connexin 43 showed all positive. With flow cytometry, the percentage of cTnT positive cells was 7.43% ± 0.02%before induction, but it was 49.64% ± 0.05% after induction. During differentiation, 1 814 differentially expressed geneswere reported by gene chi ps. Of them, 647 genes were divided into 5 groups with hierarchical clustering. They had variousbiological functions, involving signal transduction, cell metabol ism, prol iferation, differentiation, development, andtopogenesis. Conclusion hBMSCs can differentiate into cardiomyogenic cells with the induction of 5-aza in vitro. Multi plegenes related with signal transduction, transcri ption, and growth factors are involved during this process.