Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
1.
Acta Pharmaceutica Sinica B ; (6): 1671-1685, 2023.
Article in English | WPRIM | ID: wpr-982808

ABSTRACT

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC50 > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

2.
China Journal of Chinese Materia Medica ; (24): 5294-5303, 2023.
Article in Chinese | WPRIM | ID: wpr-1008727

ABSTRACT

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.


Subject(s)
Humans , NF-kappa B/metabolism , Interleukin-10 , Nucleus Pulposus/metabolism , Tumor Necrosis Factor-alpha/metabolism , Aggrecans/metabolism , Toll-Like Receptor 4/metabolism , RNA, Messenger/metabolism
3.
China Journal of Chinese Materia Medica ; (24): 4852-4863, 2023.
Article in Chinese | WPRIM | ID: wpr-1008655

ABSTRACT

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.


Subject(s)
Animals , Mice , Network Pharmacology , Vascular Endothelial Growth Factor A , Molecular Docking Simulation , Arthritis, Rheumatoid/genetics , Tumor Necrosis Factor-alpha , NF-kappa B , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional
4.
Chinese Journal of Trauma ; (12): 307-313, 2022.
Article in Chinese | WPRIM | ID: wpr-932244

ABSTRACT

Objective:To investigate the risk factors of cement vascular leakage after vertebral augmentation for osteoporotic vertebral compression fracture (OVCF).Methods:A case-control study was conducted to analyze the clinical data of 217 patients with OVCF undergone vertebral augmentation [percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP)] in First and Second Affiliated Hospital of Kunming Medical University from October 2019 to October 2020. There were 79 males and 138 females, at the age range of 58-88 years [(73.1±6.9)years]. According to the occurrence of bone cement vascular leakage, the patients were divided into vascular leakage group ( n=39) and vascular leakage free group ( n=178). The gender, age, bone mineral density, time from injury to operation, anatomical position of injured vertebrae, degree of vertebral compression, integrity of posterior wall, intravertebral fissure sign, vertebrobasilar venous foramen, surgical approach, surgical method, cement injection period, cement injection speed, cement injection volume and cement injection area were recorded. Univariate analysis was used to detect the correlation of those indices with cement vascular leakage after vertebral augmentation. Multivariate Logistic regression analysis was used to identify the independent risk factors for cement vascular leakage after vertebral augmentation. Results:Univariate analysis showed that there was a correlation of cement vascular leakage after vertebral augmentation with time from injury to operation, degree of vertebral compression, integrity of posterior wall, intravertebral fissure sign, vertebrobasilar venous foramen, surgical method, cement injection period, cement injection speed, cement injection volume and cement injection area (all P<0.05), apart from gender, age, bone mineral density, anatomical position of injured vertebrae or surgical approach (all P>0.05). Multivariate Logistic regression analysis showed intravertebral fissure sign ( OR=7.00, 95% CI 1.57-31.30, P<0.05), vertebrobasilar venous foramen ( OR=7.52, 95% CI 1.94-29.16, P<0.01), PVP ( OR=10.98, 95% CI 2.51-47.94, P<0.01), injection of cement in thinning period ( OR=5.91, 95% CI 1.45-24.15, P<0.05), injection of large volume of cement ( OR=3.60, 95% CI 1.70-7.65, P<0.01) and marginal injection of cement ( OR=24.80, 95% CI 5.28-116.37, P<0.01) were significantly associated with cement vascular leakage after vertebral augmentation for OVCF. Conclusion:Intravertebral fissure sign, vertebrobasilar venous foramen, PVP, injection of cement in thinning period, injection of large volume of cement and marginal injection of cement are independent risk factors for cement vascular leakage after vertebral augmentation for OVCF.

5.
Chinese Journal of Orthopaedics ; (12): 1283-1291, 2022.
Article in Chinese | WPRIM | ID: wpr-957123

ABSTRACT

Objective:To explore the risk factors of adjacent segment diseases (ASDis) after lumbar fusion, summarize the prevention strategies and provide reference for clinical treatment.Methods:All of 258 patients who underwent lumbar interbody fusion from March 2014 to March 2019 were retrospectively analyzed, including 95 males and 163 females, the age of whom was 61.8±8.4 years (range, 39-77 years). The patients were divided into ASDis group and non-ASDis group according to whether ASDis occurred at the follow-up of 24 months after operation. The patient's individual factors [gender, age, body mass index (BMI), main diagnosis, preoperative paraspinal muscle fatty degree, etc.] and surgical factors (operation type, fixed segment, fusion segment, etc.), sagittal parameters [lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL] were recorded. After univariate analysis of potential risk factors, the factors with P<0.05 were substituted into logistic regression model for multivariate analysis to determine the risk factors of ASDis after lumbar fusion. Results:ASDis occurred in 24 patients after lumbar fusion, with an incidence of 9.3% (24/258); univariate analysis showed that age ≥ 60 years old, complicated with osteoporosis, preoperative fatty degree of paraspinal muscle (GCS grade≥3), PLIF operation, suspension fixation, total laminectomy and multi-segment fusion (≥ 3 segments) were the potential risk factors for ASDis after operation (P<0.05); Gender, education level, partner status, type of work, BMI, obesity (BMI≥24 kg/m 2) , smoking, use of bisphosphonates, concomitant lumbar spinal stenosis, lumbar lordosis angle, pelvic incidence angle, pelvic tilt angle, sacral slope angle, and PI-LL had no significant correlation with ASDis. Logistic regression analysis showed that age ≥ 60 years ( OR=5.63, 95% CI: 1.56, 20.29, P=0.008), preoperative paravertebral muscle fatty GCS ≥ 3 ( OR=4.82, 95% CI: 1.36, 17.13, P=0.015), combined with osteoporosis ( OR=14.04, 95% CI: 2.53, 77.79, P=0.002), PLIF ( OR=9.69, 95% CI: 1.91, 49.03, P=0.001), and multi-segment fixation ( OR=9.36, 95% CI: 1.77, 49.41, P=0.008) were the risk factors for ASDis after lumbar fusion; Incomplete laminectomy ( OR=0.09, 95% CI: 0.02, 0.37, P=0.001) and suspension fixation ( OR=0.16, 95% CI: 0.02, 0.94, P=0.042) were the protective factors of ASDis after lumbar fusion. Conclusion:The patients with age ≥ 60 years old, osteoporosis and preoperative paraspinal muscle fatty degree ≥ 3 grade GCS should be more careful in choosing the surgical methods, and try to choose transforaminal interbody fusion, posterolateral fusion, short segment fusion, decompression with preservation of vertebral lamina, suspension fixation and other surgical methods to reduce the incidence of postoperative ASDis.

6.
Chinese Medical Journal ; (24): 1415-1421, 2020.
Article in English | WPRIM | ID: wpr-827573

ABSTRACT

BACKGROUND@#Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.@*METHODS@#CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.@*RESULTS@#Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.@*CONCLUSION@#Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

7.
Chinese Medical Journal ; (24): 2653-2659, 2020.
Article in English | WPRIM | ID: wpr-877873

ABSTRACT

BACKGROUND@#Liver fibrosis (LF) continues to develop and eventually progresses to cirrhosis. However, LF and early-stage cirrhosis (ESC) can be reversed in some cases, while advanced cirrhosis is almost impossible to cure. Advances in quantitative imaging techniques have made it possible to replace the gold standard biopsy method with non-invasive imaging, such as radiomics. Therefore, the purpose of this study is to develop a radiomics model to identify LF and ESC.@*METHODS@#Patients with LF (n = 108) and ESC (n = 116) were enrolled in this study. As a control, patients with healthy livers were involved in the study (n = 145). Diffusion-weighted imaging (DWI) data sets with three b-values (0, 400, and 800 s/mm) of enrolled cases were collected in this study. Then, radiomics features were extracted from manually delineated volumes of interest. Two modeling strategies were performed after univariate analysis and feature selection. Finally, an optimal model was determined by the receiver operating characteristic area under the curve (AUC).@*RESULTS@#The optimal models were built in plan 1. For model 1 in plan 1, the AUCs of the training and validation cohorts were 0.973 (95% confidence interval [CI] 0.946-1.000) and 0.948 (95% CI 0.903-0.993), respectively. For model 2 in plan 1, the AUCs of the training and validation cohorts were 0.944, 95% CI 0.905 to 0.983, and 0.968, 95% CI 0.940 to 0.996, respectively.@*CONCLUSIONS@#Radiomics analysis of DWI images allows for accurate identification of LF and ESC, and the non-invasive biomarkers extracted from the functional DWI images can serve as a better alternative to biopsy.


Subject(s)
Humans , Diffusion Magnetic Resonance Imaging , Liver Cirrhosis/diagnostic imaging , Machine Learning , ROC Curve , Retrospective Studies
8.
Chinese Journal of Hospital Administration ; (12): 48-51, 2018.
Article in Chinese | WPRIM | ID: wpr-665811

ABSTRACT

The hospital improved its rationality of medication by means of better pharmaceutical management ,full-course supervision of drug use ,and clarified responsibility system. It holds that IT means can play an early warning role for the rational medication ,while orchestrated work of section , departments and measured can improve the rationality and ensure patient safety .

9.
Chinese Journal of Tissue Engineering Research ; (53): 6333-6338, 2015.
Article in Chinese | WPRIM | ID: wpr-482049

ABSTRACT

BACKGROUND:Traditional internal fixation for thoracolumbar vertebral fractures easily causes poor vertebral reduction, and postoperative vertebral height loss easily appears. OBJECTIVE:To analyze the feasibility of lateral-position pedicle screw placement in spinal surgeryvia combined anterior-posterior approaches. METHODS: A total of 36 cases undergoing spinal surgical operation in the Baoji City Chinese Medicine Hospital from February 2013 to October 2014 were enroled in this study. The patients were divided into two groups according to the method of repair. 18 patients in the control group received prone-position pedicle screw placement, and 18 patients in the experimental group received lateral-position pedicle screw placementvia combined anterior-posterior approaches. Postoperative CT and X-ray examinations compared the adverse rate of screw placement and the rate of nerve root injury between the two groups. Operation time, length of stay, time of beginning movement, intraoperative blood loss and American Spinal Injury Association impairment scale score were compared between the two groups. RESULTS AND CONCLUSION:Significant differences in the adverse rate of screw placement and the rate of nerve root injury were detected between the two groups (P < 0.05), and the adverse rate of screw placement and the rate of nerve root injury were better in the experimental group than in the control group. Operation time, length of stay, and time of beginning movement were significantly better in the experimental group than in the control group (P < 0.05). Intraoperative blood loss was significantly lower in the experimental group than in the control group (P < 0.05). American Spinal Injury Association impairment scale scores were significantly higher in the experimental group than in the control group (P < 0.05). These findings confirm that lateral-position pedicle screw placementvia combined anterior-posterior approaches in spinal surgery can reduce intraoperative trauma, shorten the length of hospital stay, and promote functional recovery of spinal cord.

10.
Chinese Journal of Laboratory Medicine ; (12): 467-469, 2013.
Article in Chinese | WPRIM | ID: wpr-435173

ABSTRACT

Objective A comparability analysis was performed between the various parameters of the self-developed dry-type blood cell analyzer with the reference instrument (Sysmex XT-1800i).Methods In line with the evaluation program of blood cells issued by ICSH,the detection results,six parameters as HCT,Hb,GRAN (granulocytes),LM (lymphatic and monocytes),WBC and PLT,were compared between the two instruments.Some indexes of the subject instrument such as precision,comparability,outlier points,bias,etc.were analyzed and compared so as to calculate the equation of linear regression and the expected bias intervals.Results The intra and inter CV of the subject instrument about six parameters were respectively less than 5% and 6%,so it showed that the instrument had good precision.Correlation analysis showed that the classification results of HCT,Hb,GRAN and WBC had a good correlation (r =0.991,0.972,0.986,0.975,P <0.01),while that of LM and PLT were slightly lower (r =0.952,0.942,P <0.01) ; As to the medical decision level,HCT values were 14% and 70%,WBC 0.5 × 109/L and 3 ×109/L,and PLT 10 × 109/L,50 × 109/L and 100 × 109/L,and the acceptable bias of these values all fell in the confidence intervals; the values of the rest items were slightly higher than the high value of the confidence interval of expected bias.Conclusions The subject instrument produces the same results in the test of its parameters as the reference instrument Sysmex XT-1800i and therefore the two instruments are comparable.The subject instrument is particularly suitable for field rapid detection.

11.
Chinese Journal of Oncology ; (12): 114-117, 2009.
Article in Chinese | WPRIM | ID: wpr-255550

ABSTRACT

<p><b>OBJECTIVE</b>To detect serum hepatoma-specific datura stramonium lectin-tightly binding gamma-glutamyl transferase (DSA-GGT) in patients with primary hepatic cancer (PHC) by avidin-biotin ELISA method which was established in our laboratory, and carry on a study of its clinical application.</p><p><b>METHODS</b>To detect serum DSA-GGT in 45 healthy control subjects, 58 PHC patients and 203 non-PHC patients (including 36 patients with other tumors and 167 patients with benign liver diseases) with the method was established; meanwhile, AFP was detected by ELISA method.</p><p><b>RESULTS</b>38 individuals were DSA-GGT positive in 58 PHC patients, the sensitivity was 65.5%. 18 individuals were DSA-GGT positive in 203 patients without PHC, the specificity was 91.1%. The sensitivity and specificity of AFP in diagnosis of PHC patients was 69.0% and 90.6%, respectively. The sensitivity and specificity of combination of DSA-GGT and AFP was 93.1% and 85.7%, respectively. The average intra-CV and inter-CV of DSA-GGT ELISA was 8.9% and 11.5%, respectively.</p><p><b>CONCLUSION</b>The sensitivity and specificity of DSA-GGT ELISA method established in our lab is similar with that of AFP assay and the accuracy is good. Combination of DSA-GGT and AFP may improve the diagnostic sensitivity. The method should be potentially as a new way to improve diagnosis of PHC.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Avidin , Biotin , Carcinoma, Hepatocellular , Blood , Diagnosis , Enzyme-Linked Immunosorbent Assay , Methods , Liver Neoplasms , Blood , Diagnosis , Sensitivity and Specificity , alpha-Fetoproteins , gamma-Glutamyltransferase , Blood
SELECTION OF CITATIONS
SEARCH DETAIL