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1.
Int J Cardiol ; 381: 88-93, 2023 06 15.
Article in English | MEDLINE | ID: mdl-36914072

ABSTRACT

BACKGROUND: The aim of this study was to investigate the clinical characteristics of patients between active and inactive Takayasu's arteritis with pulmonary artery involvement (PTA) and to identify better markers of disease activity in these patients. METHODS: Sixty-four PTA patients in Beijing Chao-yang hospital (2011 to 2021) were included. According to National Institutes of Health criteria, 29 patients were in active stage and 35 were in inactive stage. Their medical records were collected and analyzed. RESULTS: Compared with inactive group, patients in active group were younger. More patients in active stage presented fever (41.38% vs 5.71%), chest pain (55.17% vs 20%), increased C-reactive protein (2.91 vs 0.46 mg/L), erythrocyte sedimentation rate (35.0 vs 9 mm/h), and platelet count (291 vs 221 × 109/L). Pulmonary artery wall thickening was more common in active group (51.72% vs 11.43%). These parameters were restored after treatment. The incidence of pulmonary hypertension was comparable between groups (34.48% vs 51.43%), but patients in active group had lower pulmonary vascular resistance (PVR) (361.0 vs 891.0 dyn·s·cm-5) and higher cardiac index (2.76 ± 0.72 vs 2.01 ± 0.58 L/min/m2). On multivariate logistic regression analysis, chest pain [odds ratio (OR) 9.37, 95%CI (1.98-44.38), P = 0.005], increased platelet count (>242.5 × 109/L) [OR 9.03, 95%CI (2.10-38.87), P = 0.003] and pulmonary artery wall thickening [OR 7.08, 95%CI (1.44-34.89), P = 0.016] were independently associated with disease activity. CONCLUSION: Chest pain, increased platelet count, and pulmonary artery wall thickening are potential new indicators of disease activity in PTA. Patients in active stage may have lower PVR and better right heart function.


Subject(s)
Hypertension, Pulmonary , Takayasu Arteritis , Humans , Takayasu Arteritis/diagnostic imaging , Pulmonary Artery/diagnostic imaging , Hypertension, Pulmonary/epidemiology , Chest Pain/diagnostic imaging , Chest Pain/epidemiology
2.
Clin Appl Thromb Hemost ; 28: 10760296221140882, 2022.
Article in English | MEDLINE | ID: mdl-36464656

ABSTRACT

BACKGROUND: Pulmonary endarterectomy (PEA) is the preferred treatment for CTEPH patients which can significantly improve symptoms and pulmonary hemodynamics. Therefore, this retrospective study evaluated the long-term outcomes after pulmonary endarterectomy (PEA) and analyze the predictors of long-term outcomes for chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: From 2002-2020, 76 CTEPH patients successfully discharged after PEA in Beijing Chaoyang Hospital were followed-up by scheduled clinical visits or telephone interviews. The follow-up time lasted for 18 years and median time was 7.29 years. RESULTS: The survival rate at 1,3,5,10,15 years postoperatively was 100.00%, 97.10%, 95.40%, 89.80% and 82.90%, respectively. Multivariate logistics regression analysis showed that postoperative mPAP (hazard ratio: 1.144; 95%confidence interval: 1.018-1.285; P = 0.023) was associated with a higher risk of late death, right atrium right and left diameters (hazard ratio: 1.113; 95%confidence interval, 1.006-1.231; P = 0.038) were associated with a higher risk of major adverse events. CONCLUSION: Pulmonary endarterectomy is an effective way to treat CTEPH. Long-term outcome is excellent for patients who undergoing pulmonary endarterectomy who survived from peri-operation time. Postoperative mPAP is a significant prognostic factor for long-term death and right atrium right and left diameters is a significant prognostic factor for major adverse events. That shows patients with high postoperative mPAP and right atrium right and left diameter should be followed up closely.


Subject(s)
Hypertension, Pulmonary , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/surgery , Retrospective Studies , Endarterectomy , Postoperative Period , Patient Discharge
4.
Metab Eng ; 67: 198-215, 2021 09.
Article in English | MEDLINE | ID: mdl-34166765

ABSTRACT

Actinomycetes are recognized as excellent producers of microbial natural products, which have a wide range of applications, especially in medicine, agriculture and stockbreeding. The three main indexes of industrialization (titer, purity and stability) must be taken into overall consideration in the manufacturing process of natural products. Over the past decades, synthetic biology techniques have expedited the development of industrially competitive strains with excellent performances. Here, we summarize various rational engineering strategies for upgrading the performance of industrial actinomycetes, which include enhancing the yield of natural products, eliminating the by-products and improving the genetic stability of engineered strains. Furthermore, the current challenges and future perspectives for optimizing the industrial strains more systematically through combinatorial engineering strategies are also discussed.


Subject(s)
Actinobacteria , Biological Products , Actinobacteria/genetics , Actinomyces , Metabolic Engineering , Synthetic Biology
5.
Bioresour Technol ; 330: 124982, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33743279

ABSTRACT

Microbial fermentation is currently still the major way to produce structural complicated clinical drugs. Yet, the low productivity and genetic instability of producing strains remain the bottlenecks in microbial pharmaceutical industry. Fidaxomicin is a microbial drug against the Clostridium difficile infection. Here, a genome-based combinatorial engineering strategy was established to improve both fidaxomicin production and the genetic stability of Actinoplanes deccanensis YP-1. Guided by genomic analysis, several genetic instability-associated elements were cumulatively deleted, generating a more genetically stable mutant. Further rational engineering approaches including elimination of a pigment pathway, duplication of the fidaxomicin gene cluster, overexpression of a positive regulator and optimization of the fermentation medium, led to an overall 27-folds improvement in fidaxomicin production. Taken together, the genome-based rational combinatorial engineering strategy was efficient to enhance the fidaxomicin production and ameliorate the genetic stability of YP-1, it can also be widely used in other industrial actinomycetes for strain improvement.


Subject(s)
Actinoplanes , Clostridioides difficile , Aminoglycosides , Anti-Bacterial Agents , Fidaxomicin
6.
Mol Med Rep ; 23(2)2021 02.
Article in English | MEDLINE | ID: mdl-33313943

ABSTRACT

Pulmonary hypertension (PH) is a life­threatening disease that often involves vascular remodeling. Although pulmonary arterial smooth muscle cells (PASMCs) are the primary participants in vascular remodeling, their biological role is not entirely clear. The present study analyzed the role of enhancer of zeste homolog 2 (EZH2) in vascular remodeling of PH by investigating the behavior of PASMCs. The expression levels of EZH2 in PASMCs in chronic thromboembolic pulmonary hypertension (CTEPH), a type of PH, were detected. The role of EZH2 in PASMC migration was investigated by wound­healing assay following overexpression and knockdown. Functional enrichment analysis of the whole­genome expression profiles of PASMCs with EZH2 overexpression was performed using an mRNA Human Gene Expression Microarray. Quantitative (q)PCR was performed to confirm the results of the microarray. EZH2 expression levels increased in CTEPH cell models. The overexpression of EZH2 enhanced PASMC migration compared with control conditions. Functional enrichment analysis of the differentially expressed genes following EZH2 overexpression indicated a strong link between EZH2 and the immune inflammatory response and oxidoreductase activity in PASMCs. mRNA expression levels of superoxide dismutase 3 were verified by qPCR. The results suggested that EZH2 was involved in the migration of PASMCs in PH, and may serve as a potential target for the treatment of PH.


Subject(s)
Enhancer of Zeste Homolog 2 Protein/biosynthesis , Enhancer of Zeste Homolog 2 Protein/genetics , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/metabolism , Muscle, Smooth, Vascular/metabolism , Pulmonary Artery/metabolism , Cell Line , Cell Movement/genetics , Female , Gene Expression Regulation , Gene Knockdown Techniques , Gene Ontology , Humans , Hypertension, Pulmonary/chemically induced , Inflammation/genetics , Inflammation/immunology , Male , Middle Aged , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism , NADPH Oxidase 1/metabolism , Oxidoreductases/metabolism , Superoxide Dismutase/metabolism , Tissue Array Analysis , Transcriptome , Vascular Remodeling/genetics
7.
J Thromb Thrombolysis ; 51(3): 703-710, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32894400

ABSTRACT

A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.


Subject(s)
Endarterectomy/adverse effects , Fondaparinux/administration & dosage , Heparin/adverse effects , Hypertension, Pulmonary , Platelet Count , Postoperative Complications , Thrombocytopenia , Adult , China/epidemiology , Cohort Studies , Endarterectomy/methods , Factor Xa Inhibitors/administration & dosage , Female , Heparin/administration & dosage , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/prevention & control , Male , Middle Aged , Platelet Count/methods , Platelet Count/statistics & numerical data , Postoperative Complications/blood , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/surgery , Risk Adjustment/methods , Thrombocytopenia/blood , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology
8.
Appl Microbiol Biotechnol ; 103(18): 7583-7596, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31327020

ABSTRACT

Fidaxomicin, an 18-membered macrolide antibiotic, is highly active against Clostridium difficile, the most common cause of diarrhea in hospitalized patients. Though the biosynthetic mechanism of fidaxomicin has been well studied, little is known about its regulatory mechanism. Here, we reported that FadR1, a LAL family transcriptional regulator in the fidaxomicin cluster of Actinoplanes deccanensis Yp-1, acts as an activator for fidaxomicin biosynthesis. The disruption of fadR1 abolished the ability to synthesize fidaxomicin, and production could be restored by reintegrating a single copy of fadR1. Overexpression of fadR1 resulted in an approximately 400 % improvement in fidaxomicin production. Electrophoretic mobility shift assays indicated that fidaxomicin biosynthesis is under the control of FadR1 through its binding to the promoter regions of fadM, fadA1-fadP2, fadS2-fadC, and fadE-fadF, respectively. And the conserved binding sites of FadR1 within the four promoter regions were determined by footprinting experiment. All results indicated that fadR1 encodes a pathway-specific positive regulator of fidaxomicin biosynthesis and upregulates the transcription levels of most of genes by binding to the four above intergenic regions. In summary, we not only clearly elucidate the regulatory mechanism of FadR1 but also provide strategies for the construction of industrial high-yield strain of fidaxomicin.


Subject(s)
Actinoplanes/metabolism , Anti-Bacterial Agents/biosynthesis , Bacterial Proteins/metabolism , Fidaxomicin/metabolism , Repressor Proteins/metabolism , Actinoplanes/genetics , Bacterial Proteins/genetics , Biosynthetic Pathways , Clostridioides difficile/drug effects , Gene Expression Regulation, Bacterial , Repressor Proteins/genetics
9.
J Neuropathol Exp Neurol ; 78(8): 685-693, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31271432

ABSTRACT

Solitary fibrous tumor/hemangiopericytomas (SFT/HPCs) are mesenchymal tumors characterized by "staghorn" blood vessels and collagen deposition. Little is known about SFT/HPCs with papillary architecture. We summarized the clinicopathologic features of 12 patients with papillary SFT/HPCs (8 males and 4 females; median age: 59 years), including 8 previously reported cases. Tumors were present in the meninges (75%, 9/12), adrenal gland (8%, 1/12), orbit (8%, 1/12), or spinal canal (8%, 1/12). Six tumors (50%) had a true papillary architecture with fibrovascular cores and 6 tumors (50%) had a pseudopapillary architecture with vascular cores. Nuclear staining for STAT6 was present in all tested tumors (10/10). RT-PCR indicated NAB2 ex6-STAT6 ex17 fusion in 4 tumors (80%, 4/5) and NAB2 ex4-STAT6 ex2 fusion in 1 tumor (20%, 1/5). Five patients (42%, 5/12), all with tumors in the meninges, developed local recurrence at a median of 61 months after surgery (range: 56-165 months; mean: 88.6 months). These results indicated that the papillary architecture is a morphological form of SFT/HPCs. The recognition of this pattern, with appropriate immunohistochemical analysis and assessment of NAB2-STAT6 fusion, should facilitate the distinction of these rare neoplasms from morphologically similar tumors in the meninges, lung, pleura, and soft tissue.

10.
Neural Regen Res ; 14(2): 306-312, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30531014

ABSTRACT

Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic (phrenic nerve group), intercostal (intercostal nerve group) or thoracodorsal nerves (thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study established an optimized animal model in which suturing the nerve graft to the distal site of the musculocutaneous nerve anastomosis prevented the inhibition of recovery from scar compression.

11.
Neural Regen Res ; 13(5): 862-868, 2018 May.
Article in English | MEDLINE | ID: mdl-29863017

ABSTRACT

Exogenous discharge can positively promote nerve repair. We, therefore, hypothesized that endogenous discharges may have similar effects. The phrenic nerve and intercostal nerve, controlled by the respiratory center, can emit regular nerve impulses; therefore these endogenous automatically discharging nerves might promote nerve regeneration. Action potential discharge patterns were examined in the diaphragm, external intercostal and latissimus dorsi muscles of rats. The phrenic and intercostal nerves showed rhythmic clusters of discharge, which were consistent with breathing frequency. From the first to the third intercostal nerves, spontaneous discharge amplitude was gradually increased. There was no obvious rhythmic discharge in the thoracodorsal nerve. Four animal groups were performed in rats as the musculocutaneous nerve cut and repaired was bland control. The other three groups were followed by a side-to-side anastomosis with the phrenic nerve, intercostal nerve and thoracodorsal nerve. Compound muscle action potentials in the biceps muscle innervated by the musculocutaneous nerve were recorded with electrodes. The tetanic forces of ipsilateral and contralateral biceps muscles were detected by a force displacement transducer. Wet muscle weight recovery rate was measured and pathological changes were observed using hematoxylin-eosin staining. The number of nerve fibers was observed using toluidine blue staining and changes in nerve ultrastructure were observed using transmission electron microscopy. The compound muscle action potential amplitude was significantly higher at 1 month after surgery in phrenic and intercostal nerve groups compared with the thoracodorsal nerve and blank control groups. The recovery rate of tetanic tension and wet weight of the right biceps were significantly lower at 2 months after surgery in the phrenic nerve, intercostal nerve, and thoracodorsal nerve groups compared with the negative control group. The number of myelinated axons distal to the coaptation site of the musculocutaneous nerve at 1 month after surgery was significantly higher in phrenic and intercostal nerve groups than in thoracodorsal nerve and negative control groups. These results indicate that endogenous autonomic discharge from phrenic and intercostal nerves can promote nerve regeneration in early stages after brachial plexus injury.

12.
Thromb Res ; 166: 10-18, 2018 06.
Article in English | MEDLINE | ID: mdl-29649767

ABSTRACT

BACKGROUND: Despite the availability of clinical practice guidelines (CPGs), the risk of death or thromboembolic complication associated with heparin-induced thrombocytopenia (HIT) remains high. Our aim was to systematically review the quality of CPGs for HIT and summarize the recommendations. METHODS: CPGs for HIT were systematically searched on PubMed, Embase, guidelines' websites, and Google up to August 6, 2017. Independently, three appraisers assessed the quality of CPGs using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument and extracted the data. Recommendations were summarized, and a comparative study was conducted to analyze the consistency among guidelines. RESULTS: A total of 11 CPGs were evaluated. The quality assessed by AGREE II varied widely, not only between domains within guidelines, but also between guidelines across domains. The domain of scope and purpose and clarity of presentation obtained the highest median scores, while the domain of rigor of development and editorial independence obtained the lowest median scores. The ACCP guideline and BSH guideline were recommended for use in dealing with HIT, achieving a score of at least 50% in all six AGREE II domains. Recommendations across guidelines were inconsistent, especially in the choice of non-heparin anticoagulant for HIT. CONCLUSIONS: Future HIT guidelines should place more emphasis on methodological quality and improve efforts to include cost and local availability of drugs when providing recommendations.


Subject(s)
Guidelines as Topic , Heparin/adverse effects , Thrombocytopenia/chemically induced , Humans , Thrombocytopenia/pathology
13.
Blood Coagul Fibrinolysis ; 29(3): 275-281, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29538004

ABSTRACT

: Acute pulmonary embolism is a common disease, which is associated with high mortality and morbidity. There is significant relationship between haptoglobin and pulmonary embolism, however, the usefulness of haptoglobin as a biomarker for the diagnosis of pulmonary embolism remains poorly defined. The aim of the present study was to investigate the change and clinical diagnostic value of haptoglobin in pulmonary embolism. A comparative proteomic analysis was used for clinical screening of serum proteins in 18 patients (9 patients with pulmonary embolism and 9 controls). ELISA was used to validate the dysregulated proteins in 48 patients (24 patients with pulmonary embolism and 24 controls). Immunohistochemical staining was performed to detect the expression of haptoglobin in pulmonary artery of both groups. The diagnostic value of the differential protein and its association with the severity of pulmonary embolism were evaluated. Eight proteins showed significant changes in serum of pulmonary embolism patients. Haptoglobin, as one of the eight differential proteins, was significantly overexpressed in the serum of pulmonary embolism patients. In accordance, the expression of haptoglobin was increased in pulmonary artery of pulmonary embolism patients. The ROC curve showed that serum haptoglobin was a specific parameter in the diagnosis of pulmonary embolism with an area under the curve of 0.764 (95% confidence interval, 0.622-0.906; P < 0.01); in particular, the haptoglobin level at least 256.74 mg/l was the most useful cut-off value, with the sensitivity of 62% and specificity of 83%. Increased haptoglobin level may be an acceptable diagnostic parameter for pulmonary embolism.


Subject(s)
Haptoglobins/analysis , Pulmonary Embolism/diagnosis , Acute Disease , Aged , Biomarkers/blood , Case-Control Studies , Female , Humans , Male , Middle Aged , Pulmonary Artery/metabolism , Sensitivity and Specificity
14.
Am J Physiol Lung Cell Mol Physiol ; 314(2): L276-L286, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29122755

ABSTRACT

Pulmonary arterial smooth muscle cell (PASMC) migration plays a key role in vascular remodeling, which occurs during development of chronic thromboembolic pulmonary hypertension (CTEPH). Activation of the renin-angiotensin system (RAS) contributes to vascular remodeling observed in many diseases, including idiopathic pulmonary arterial hypertension. However, the role of RAS imbalance in CTEPH has not been characterized. Here, we hypothesize that RAS imbalance regulates vascular remodeling by promoting PASMC migration in CTEPH. Serum renin and angiotensin II levels in patients with CTEPH were quantified by ELISA. The pulmonary endarterectomy tissues were stained and analyzed by immunohistochemistry. PASMCs were isolated and verified by immunofluorescence staining. PASMC migration was determined by Transwell assay. Phosphorylation and protein level were detected by Western blotting. Serum levels of renin and angiotensin II were increased in patients with CTEPH {renin [median (25th percentile, 75th percentile) in pg/ml], 1,199.94 [690.85, 1,656.90] vs. 595.43 [351.48, 936.43], P < 0.001; angiotensin II [in pg/ml], 63.97 [45.97, 345.24] vs. 56.85 [11.20, 90.37], P < 0.05}. The migration of PASMCs isolated from patients with CTEPH was enhanced compared with control. Angiotensin II promoted the migration of PASMCs via activation of angiotensin II receptor 1 and phosphorylation of ERK1/2, whereas angiotensin-(1-7) counteracted this effect through activation of the Mas receptor and ERK1/2. These results demonstrate that the renin-angiotensin system regulates migration of PASMCs from patients with CTEPH via the ERK1/2 pathway. Our findings suggest that angiotensin-(1-7) or reagents targeting the renin-angiotensin system will be beneficial in the development of novel therapies for CTEPH.


Subject(s)
Cell Movement , Hypertension, Pulmonary/pathology , Muscle, Smooth, Vascular/pathology , Pulmonary Artery/pathology , Thromboembolism/pathology , Angiotensin II/metabolism , Cell Proliferation , Cells, Cultured , Female , Humans , Hypertension, Pulmonary/metabolism , MAP Kinase Signaling System , Male , Middle Aged , Mitogen-Activated Protein Kinases , Muscle, Smooth, Vascular/metabolism , Phosphorylation , Pulmonary Artery/metabolism , Renin/metabolism , Renin-Angiotensin System , Signal Transduction , Thromboembolism/metabolism
15.
Biochem Biophys Res Commun ; 495(3): 2369-2375, 2018 01 15.
Article in English | MEDLINE | ID: mdl-29229385

ABSTRACT

Circular RNAs (circRNAs) is a novel type of non-coding RNAs generated from back splicing, which has been verified to mediate multiple tumorigenesis. However, the role of circRNA in osteosarcoma is still unclear. In the present study, we preliminarily screened the circRNAs expression profiles in osteosarcoma and investigated the potential regulation mechanism. The circRNAs expression profiles in osteosarcoma were screened using circRNA microarray analysis, and results showed that there were 1152 circRNAs up-regulated and 915 circRNAs down-regulated in tumor tissue compared to adjacent tissue. Hsa_circ_0001564, located at 5q35.3 and its associated-gene symbol is CANX, was one of the significantly overexpressed circRNAs in osteosarcoma tissue, as well as in osteosarcoma cell lines. In functional experiments, hsa_circ_001564 knockdown significantly suppressed the proliferation activity, induced cell cycle arrest in G0/G1 phase, and promoted apoptosis in HOS and MG-63 cells. Subsequently, we explored the probable mechanism of hsa_circ_001564, and fortunately, bioinformatics analysis revealed that miR-29c-3p contained the complementary binding region with hsa_circ_0001564, which was confirmed by dual-luciferase reporter assay. Moreover, rescue experiments illustrated that miR-29c-3p could reverse the oncogenesis effect of hsa_circ_001564. Our study discovers that hsa_circ_0001564 acts as miR-29c-3p sponge to mediate the tumorigenicity, which could act as a potential biomarker for the osteosarcoma and provide a novel insight for competing endogenous RNAs (ceRNAs) mechanism in osteosarcoma.


Subject(s)
Apoptosis/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , MicroRNAs/genetics , Osteosarcoma/genetics , Osteosarcoma/pathology , RNA/genetics , Carcinogenesis/genetics , Humans , RNA, Circular , Tumor Cells, Cultured
16.
Tumour Biol ; 39(7): 1010428317709991, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28695772

ABSTRACT

Circular RNAs are novel identified type of endogenous non-coding RNAs, which exert vital functions in human and animals. However, the in-depth role of circular RNAs in the progression of tumorigenesis, especially osteosarcoma, is still undefined. Our preliminary study had found that cir-GLI2 was significantly upregulated in osteosarcoma tissues compared to adjacent non-tumor tissue. Moreover, cir-GLI2 silencing could effectively suppress the proliferation, migration, and invasion capacity of osteosarcoma cells, indicating the tumor-promoting role. Besides, bioinformatics analysis and luciferase reporter assay predicted the direct binding to miR-125b-5p, which has been reported to function as a tumor suppressor in osteosarcoma. Furthermore, functional experiments validated that cir-GLI2 exerted the tumor-promoting effects on osteosarcoma cells via negatively targeting miR-125b-5p. In conclusion, our study demonstrated that cir-GLI2 acts as an oncogenic circular RNA in osteosarcoma genesis, providing a novel diagnostic and therapeutic target for osteosarcoma.


Subject(s)
Kruppel-Like Transcription Factors/genetics , MicroRNAs/genetics , Nuclear Proteins/genetics , Osteosarcoma/genetics , RNA/genetics , Apoptosis/genetics , Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness/genetics , Osteosarcoma/pathology , RNA, Circular , RNA-Binding Proteins/genetics , Zinc Finger Protein Gli2
17.
Heart Lung Circ ; 26(8): e54-e58, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28314671

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. METHODS: A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. RESULTS: Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. CONCLUSIONS: Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful.


Subject(s)
Arterio-Arterial Fistula , Computed Tomography Angiography , Dyspnea , Embolization, Therapeutic , Hypertension, Pulmonary , Pulmonary Artery/diagnostic imaging , Adult , Arterio-Arterial Fistula/complications , Arterio-Arterial Fistula/diagnostic imaging , Arterio-Arterial Fistula/therapy , Contrast Media/administration & dosage , Dyspnea/diagnostic imaging , Dyspnea/etiology , Dyspnea/therapy , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/therapy , Male
18.
Chin Med J (Engl) ; 130(4): 382-391, 2017 02 20.
Article in English | MEDLINE | ID: mdl-28218209

ABSTRACT

BACKGROUND: The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls. METHODS: We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test. RESULTS: The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381). CONCLUSIONS: The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.


Subject(s)
Familial Primary Pulmonary Hypertension/drug therapy , Hypertension, Pulmonary/drug therapy , Administration, Inhalation , Adult , Aged , Arterial Pressure/drug effects , Atrial Natriuretic Factor/metabolism , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/therapeutic use , Endarterectomy , Familial Primary Pulmonary Hypertension/physiopathology , Female , Hemodynamics/drug effects , Humans , Hypertension, Pulmonary/physiopathology , Iloprost/administration & dosage , Iloprost/therapeutic use , Male , Middle Aged , Protein Precursors/metabolism , Retrospective Studies , Software , Vasodilator Agents/administration & dosage , Vasodilator Agents/therapeutic use
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(6): 829-32, 2016 Jun.
Article in Chinese | MEDLINE | ID: mdl-27320887

ABSTRACT

OBJECTIVE: To evaluate the mid-term clinical outcome of endoscopic greater saphenous vein harvesting (EVH) in coronary artery bypass grafting (CABG). Method A total of 205 patients receiving off-pump CABG between July, 2012 and April, 2013 at our department were enrolled in this study, including 66 patients (35 male and 31 female patients with a mean age of 60.3±7.92 years) undergoing EVH and 139 patients (109 male and 30 female patients with a mean age of 59.20±8.37 years) undergoing open greater saphenous vein harvesting (OVH). RESULTS: The surgical procedures were completed smoothly in all the cases. The perioperative mortality rates was 3.03% (2/66) in EVH group, as compared with 3.60% (5/139) in OVH group (P=1.00). Acute myocardial infarction (AMI) occurred during the perioperative period in 3 (2.16%) patients in OVH group and in 1 (1.52%) patient in EVH group. Perioperative low cardiac output syndrome was diagnosed in 4 (2.88%) patients in OVH group and in 2 (3.03%) in EVH group (P>0.05). During the follow-up, 8 (8.80%) patients in OVH group and 5 (8.06%) in EVH group had recurrent angina (P=0.93). No patients experienced AMI during the follow-up. The 2-year patency rate of the venous grafts was 83.59% in OVH group and 82.22% in EVH group (P=0.73). CONCLUSION: EVH has significant advantage in reducing the complications of the incision in the lower limbs. The mid-term patency rates of venous grafts are similar between OVH and EVH, but the long-term patency rate needs further evaluation.


Subject(s)
Coronary Artery Bypass , Saphenous Vein/transplantation , Tissue and Organ Harvesting , Vascular Surgical Procedures , Aged , Endoscopy , Female , Humans , Lower Extremity , Male , Middle Aged
20.
Neuroreport ; 27(1): 12-7, 2016 Jan 06.
Article in English | MEDLINE | ID: mdl-26544683

ABSTRACT

The transfer of a contralateral healthy seventh cervical spinal nerve root (cC7) to the recipient nerve in the injured side is considered a promising procedure for restoration of the physiological functions of an injured hand after brachial plexus root avulsion injury (BPAI). Growing evidence shows that transhemispheric cortical reorganization plays an important role in the functional recovery of the injured arm after cC7 nerve transfer surgery. However, the molecular mechanism underlying the transhemispheric cortical reorganization after cC7 transfer remains elusive. In the present study, we investigated the expression of miR-132, miR-134, and miR-485 in the rat primary motor cortex after cC7 transfer following BPAI by quantitative PCR. The results demonstrated the dynamic alteration in the expression of miR-132, miR-134, and miR-485 in the primary motor cortex of rats after cC7 transfer following BPAI. It indicates that microRNAs are involved in the dynamic transhemispheric functional reorganization after cC7 root transfer following BPAI. Together, this study is the first to provide evidence for the involvement of microRNAs during dynamic transhemispheric functional reorganization after cC7 transfer following BPAI. The results are useful for understanding the mechanism underlying transhemispheric functional reorganization after contralateral seventh cervical spinal nerve root transfer following BPAI.


Subject(s)
Brachial Plexus/injuries , Brachial Plexus/surgery , MicroRNAs/metabolism , Motor Cortex/metabolism , Neuronal Plasticity/physiology , Animals , Brachial Plexus/metabolism , Cervical Vertebrae , Disease Models, Animal , Functional Laterality/physiology , Gene Expression , Male , Nerve Transfer , Peripheral Nerve Injuries/metabolism , Peripheral Nerve Injuries/surgery , Polymerase Chain Reaction , Random Allocation , Rats, Sprague-Dawley , Spinal Nerve Roots/metabolism , Spinal Nerve Roots/surgery
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