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Patients with glioblastoma (GBM) generally have a bad prognosis and short overall survival after being treated with surgery, chemotherapy or radiotherapy due to the histological heterogeneity, strong invasive ability and rapid postoperative recurrence of GBM. The components of GBM cell-derived exosome (GBM-exo) can regulate the proliferation and migration of GBM cell via cytokines, miRNAs, DNA molecules and proteins, promote the angiogenesis via angiogenic proteins and non-coding RNAs, mediate tumor immune evasion by targeting immune checkpoints with regulatory factors, proteins and drugs, and reduce drug resistance of GBM cells through non-coding RNAs. GBM-exo is expected to be an important target for the personalized treatment of GBM and a marker for diagnosis and prognosis of this kind of disease. This review summarizes the preparation methods, biological characteristics, functions and molecular mechanisms of GBM-exo on cell proliferation, angiogenesis, immune evasion and drug resistance of GBM to facilitate developing new strategies for the diagnosis and treatment of GBM.
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Humans , Glioblastoma/genetics , Exosomes/metabolism , MicroRNAs/metabolism , Prognosis , Cell Proliferation , Brain Neoplasms/genetics , Cell Line, TumorABSTRACT
In recent years, the use of fluorescent contrast agents staining to guide surgery has flourished in various fields of surgery under the concept of precision surgery, which is helpful to guide surgery and provide surgeons with actual visible fluorescence imaging.Clinically, fluorescent contrast agent can be used to display tumor’s outline with high recognition degree, guide operation in real time, locate lymph node metastasis, detect small metastases, and identify important anatomical structures during the operation to avoid possible side-injury. Great progress has been made in the study of fluorescent contrast agents that can mediate surgery, including the study and surgical application development of classical fluorescent contrast agents such as indocyanine green and methylene blue, etc, as well as the discovery and clinical application of new targeted fluorescent contrast agents such as folate receptor targeting contrast agents, monoclonal antibody based fluorescent targeting contrast agents and intelligent contrast agents, etc. This paper will review the research and surgical application of fluorescent contrast agents in two aspects: classical fluorescent contrast agents and new targeted fluorescent contrast agents.
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Objective@#To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL).@*Methods@#A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams.@*Results@#There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission.@*Conclusions@#ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.
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In recent years,the use of fluorescent contrast agents staining to guide surgery has flourished in various fields of surgery under the concept of precision surgery,which is helpful to guide surgery and provide surgeons with actual visible fluorescence imaging.Clinically,fluorescent contrast agent can be used to display tumor's outline with high recognition degree,guide operation in real time,locate lymph node metastasis,detect small metastases,and identify important anatomical structures during the operation to avoid possible side-injury.Great progress has been made in the study of fluorescent contrast agents that can mediate surgery,including the study and surgical application development of classical fluorescent contrast agents such as indocyanine green and methylene blue,etc,as well as the discovery and clinical application of new targeted fluorescent contrast agents such as folate receptor targeting contrast agents,monoclonal antibody based fluorescent targeting contrast agents and intelligent contrast agents,etc.This paper will review the research and surgical application of fluorescent contrast agents in two aspects:classical fluorescent contrast agents and new targeted fluorescent contrast agents.
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Objective:To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL).Methods:A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams.Results:There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. Conclusions:ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.
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This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in de novo acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of de novo AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing.We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. FLT3-ITD was the most common mutated gene (16.2%, 42/259), followed by CEBPA (15.1%, 39/259), NRAS (14.7%, 38/259), and NPM1 (13.5%, 35/259). Concurrence was observed in 97.1% of the NPM1 mutated cases and in 29.6% of the double mutated CEBPA cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the IDH2 gene: R140 mutations were associated with NPM1 and/or FLT3-ITD mutations, whereas R172 mutations co-occurred with DNMT3A mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with NPM1 mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , CCAAT-Enhancer-Binding Proteins , Genetics , China , DNA Mutational Analysis , GTP Phosphohydrolases , Genetics , Gene Expression Profiling , Gene Frequency , Genetic Predisposition to Disease , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute , Genetics , Membrane Proteins , Genetics , Mutation , Nuclear Proteins , Genetics , Phenotype , Retrospective Studies , fms-Like Tyrosine Kinase 3 , GeneticsABSTRACT
Acute radiation exposure usually causes severe dysfunction in various tissues of the organism, among which hematopoiesis, digestion, skin, cardiovascular and nervous system are most obviously affected, often leading to extensive apoptosis and acute radiation syndrome. Apoptosis inhibition or loss could increase proliferation of tumor cells through p53 and NF-κB pathways. Toll-like receptors ( TLRs) are a class of protein molecules involved in non-specific immunity. Up-regulation of the NF-κB pathway results in a significant increase in the radioresistance of cells. TLR4 has a basal cell radiation damage protection effect. Traditional TLR4 agonist lipopolysaccharide is limited in clinical application due to severe toxicity. Recently, some new TLRs agonists have been reported, which have protective effects against the lethal effects of ionizing radiation and lower toxic side effects. Among them, TLR2, TLR4, TLR5 and TLR9 play key roles in radiation protection, such as TLR2 receptor agonist bacterial lipoprotein (BLP), TLR4 receptor agonist heat-activated Salmonella typhimurium (HKST), TLR5 receptor agonism Bacterial flagellin and TLR9 receptor agonist. However, those different TLRs recognize specific components of the pathogen and thus initiate different downstream signaling pathways with different protective effects.
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Objective To investigate the clinical and molecular biological characteristics of mixed_phenotypic acute leukemia (MPAL) with SET_NUP214 fusion gene positive and extramedullary infiltration. Methods The clinical characteristics, diagnosis and treatment of one MPAL patient with SET_NUP214 and extramedullary infiltration who was admitted to Hebei Yanda Ludaopei Hospital in November 2017 were analyzed, and the literature was reviewed. Results The patient was diagnosed as MPAL with extramedullary infiltration. Gene detection found SET exon7_NUP214 exon17 fusion positive accompanied with PHF6, SRSF2 and NRAS mutations. After intensive chemotherapy, the patient achieved complete remission, and then received hematopoietic stem cell transplantation (HSCT), followed by early extramedullary relapse after transplantation, and achieved secondary remission after consolidation chemotherapy. Conclusions MPAL with SET_NUP214 fusion gene positive and extramedullary infiltration has a poor prognosis, and it is easy to relapse. Currently, HSCT is the best available treatment strategy for such patients.
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General anesthesia and surgery have been associated with acute cognitive impairment in several elderly individuals. Present study was conducted to determine whether the general anaesthesia exposure and cognitive dysfunction are linked or not. This is a China-based retrospective, population-based and case-control study. Using Chinese database inhabitants of Shenyang, China, incident cases detected with cognitive abnormalities between January 2007 and December 2012 were identified. With respective to every incident case, age- and gender-matched control subject was chosen among the general population pool of Shenyang inhabitants who were not having cognitive anomalies in the year. Medical records were scrutinized to examine the exposures to surgical procedures necessitating anesthesia after 45-years of age. We examined 577 cases of cognition-impaired [dementia] patients, every incident case with a conforming control subject. Among the cognitive impaired patients, 414 [71.7%] underwent 821 surgical operations needing general anesthesia exposure; of the controls, 404 [70%] underwent 833 surgical procedures. The present study found that general anaesthetic agents encounter was not markedly associated with cognitive anomalies [odds ratio, 0.87; 95% CI, 0.71-1.09; P=0.29]. Moreover, no substantial relation was observed when the anaesthetic agents encounter was measured as number of surgical operations [odds ratios [OR], 0.83, 0.89, and 1.0 for 1, 2-3, and 4 exposures, correspondingly, matched with none; P=0.52]. Our present work witnessed no substantial link between surgical procedures requiring single or multiple general anesthesia exposure post 45-years of age and cognitive dysfunction
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Lux reporter plays an important role in molecular biology,clinical microbiology and biochemical detection,owing to its high sensitivity,fast reaction and convenience.Here the component,types and characteristics of lux reporter system were introduced.Moreover,the recent advance of its application in environment detection,food safety,new drug discovery and tumor locating were reviewed.
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Objective: To explore the clinical and echocardiography characteristics between noncompaction of ventricular myocardium (NVM) and dilated cardiomyopathy (DCM) combining hypertrabeculation in order to distinguish NVM from DCM. Methods: Our research included 2 groups of patients: NVM group,n=31 and DCM combining hypertrabeculation group, n=50. The basic information as gender, age, family history, symptoms, ECG, plasma levels of BNP and echocardiography were recorded and examined in all patients; the size of cardiac chambers, myocardium, endocardium and hemodynamics were particularly focused. The trabeculation was analyzed by 17 segments method. Results:①Compared with NVM group, the patients in DCM combining hypertrabeculation group had the worse cardiac classiifcation, higher plasma levels of BNP (P 2.③The patients in DCM combining hypertrabeculation group had the less trabeculation segments (5.56 ± 1.56) and the apical was seldom involved, patients had the lower ration of NC/C as (1.91± 0.42), there was at most 1 segment with NC/C > 2. All P Conclusion: Echocardiography is a simple, practical and noninvasive method to distinguish NVM from DCM. NVM could be diagnosed by obvious left ventricular apex involvement with NC/C >2 in at least 2 segments of free ventricular walls.
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Objective To explore the effect of a new prone position for general anesthesia.Methods 50 patients in the group were made a retrospective study:All the 50 patients needed prone position surgeries under general anesthesia.After awake flexible fiberoptic intubation,with the anesthesia of thyrocricoid puncturing the intra-trachea surface,has been taken,patients lied in the prone position according to their own comfort with the guide of medical staff,which was followed by anesthesia induction and the operation.The SBP,DBP,HR and RPP were recor-ded at different point of time after patients entered the operation room.Results 33 cases of 50 patients completed the whole process successfully and the indexes at the time of the intubation had no significant difference with those at basic state(all P >0.05).17 operations suffered discomfort.The SBP,DBP,HR and RPP in these patients were (159.2 ±25.9)mmHg,(97.2 ±11.6)mmHg,(98.2 ±9)beats per minute and (16 028 ±6 725)respectively, which were higher than those at basic state(t =2.698,2.802,5.720,8.905,all P 0.05).Conclusion It is technically simple and easy to operate,the way that patients waiting for prone position surgeries lie in the prone position by themselves with awake flexible fiberoptic intubation lightens the workload of medical staff and reduces complications of the intubation,which is optional in clinical situations.
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<p><b>OBJECTIVE</b>This study investigated the effect of catheter-based renal sympathetic denervation (RDN) in pigs with rapid pacing induced heart failure.</p><p><b>METHODS</b>Heart failure was induced by rapid right ventricular pacing in 12 pigs and pigs were randomly divided into RDN group (n = 6): pacing+RDN at 7 days post pacing; control group (n = 6): pacing only. Echocardiography examination (LVEF, LVEDD and LVESD) was performed before pacing and at 1 and 2 weeks post pacing. Serum biochemical markers including renin, aldosterone and creatinine were also measured at baseline, 1 and 2 weeks after pacing. Repeated renal artery angiography was performed at 1 week after RDN. All pigs were sacrificed to examine the heart and renal pathology and renal artery sympathetic nerve staining at 2 weeks post pacing.</p><p><b>RESULTS</b>LVEF decreased 1 week after rapid pacing from (60.5 ± 6.0)% to (35.3 ± 9.8)%. LVEF was significantly higher [(42.8 ± 5.9) % vs. (33.4 ± 9.7)%, P = 0.001 8] while LVESD was significantly lower [(28.4 ± 3.7) mm vs. (33.0 ± 2.0) mm, P = 0.001 6] in the RDN group than in the control group at 2 weeks post pacing. At 2 weeks after pacing, plasma concentrations of renin and aldosterone were significantly lower in RDN group compared to the control group (all P < 0.05) . Kidney function and blood pressure were comparable between the two groups at 2 weeks post pacing. There were no signs of renal damages such as renal artery stenosis, dissection and thrombus in all pigs after 2 weeks pacing. Sympathetic neurons of adventitia were injured in RND group.</p><p><b>CONCLUSION</b>RDN could significantly improve cardiac function and attenuate left ventricular remodeling via inhibiting renin-angiotensin-aldosterone system in this pacing induced pig heart failure model.</p>
Subject(s)
Animals , Female , Male , Cardiac Pacing, Artificial , Catheter Ablation , Methods , Disease Models, Animal , Heart Failure , General Surgery , Kidney , Swine , Sympathectomy , MethodsABSTRACT
Penicillium decumbens T. is an important filamentous fungus for the production of cellulases to effectively degrade lignocellulose for second generation biofuel production. In order to enhance the capability of Penicillium decumbens to produce cellulases, we constructed a creB (a deubiquitinating enzyme encoding gene) deletion cassette, and generated a creB knockout strain with homologous double crossover recombination. This mutation resulted in a detectable decrease of carbon catabolite repression (CCR) effect. The filter paper activity, endoglucanase activity, xylanase activity and exoglucanase activity of the deltacreB strain increased by 1.8, 1.71, 2.06 and 2.04 fold, respectively, when comparing with the parent strain Ku-39. A 2.68 fold increase of extracellular protein concentration was also observed. These results suggest that the deletion of creB results in CCR derepression. These data also suggest that CREB influences cellulase production of Penicillium decumbens. In generation, this study provides information that can be helpful for constructing cellulase hyper-producing strain.
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Cellulase , Endopeptidases , Genetics , Metabolism , Gene Knockout Techniques , Lignin , Metabolism , Mutant Proteins , Metabolism , Penicillium , Genetics , Recombination, Genetic , Ubiquitinated Proteins , Genetics , UbiquitinationABSTRACT
<p><b>OBJECTIVE</b>To detect occult metastases in lymph nodes from patients with colorectal carcinoma and its clinical significance.</p><p><b>METHODS</b>The metastases in 260 lymph nodes from 39 histologically verified colorectal cancer patients were studied by both hematoxylin-eosin (HE) staining and cytokeratin-20 (CK20) specific RT-PCR. Ten normal lymph nodes were served as negative controls, and HT29 colon cancer cell line and 5 colorectal cancer specimens as positive controls.</p><p><b>RESULTS</b>Ten normal lymph nodes were CK20-negative, HT29 cells and 5 tumor specimens were all CK20-positive. All 29 lymph nodes from 16 patients which confirmed metastases by HE staining exhibited CK20 positive expression; an additional 28 lymph nodes from 5 patients with no histologically detectable metastases expressed CK20 mRNA, i.e. presence of metastases. The difference of the positivity was significant (11.1% vs 21.9%, P < 0.01). According to the HE staining, the cases of Dukes' A, B, C and D were 3, 20, 12 and 4, respectively. In the 20 patients of Dukes' B stage, 5 of them had CK20-positive lymph nodes.</p><p><b>CONCLUSION</b>CK20-specific RT-PCR is a highly sensitive, specific and simple method for detecting occult metastases in lymph nodes. The detection of CK20 mRNA expression in lymph nodes is recommended to precisely determine tumor stage and postoperative adjuvant therapy for patients with colorectal cancer, and further studies should be done in future to confirm the findings.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Colorectal Neoplasms , Genetics , Pathology , Gene Expression Regulation, Neoplastic , HT29 Cells , Intermediate Filament Proteins , Genetics , Keratin-20 , Lymph Node Excision , Lymph Nodes , Metabolism , Pathology , Lymphatic Metastasis , Genetics , Pathology , RNA, Messenger , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Objective To study the radiographic findings of the chest in patients after open heart surgery and its evaluating methods.Methods 236 cases after open heart surgery were divided into 3 groups according to the date of the first postoperative chest films:0～3 d,4～7 d and 8 d or more.The findings on pre and postoperative chest films were compared in 7 aspects respectively.Results 8 typses of complications were detected including severe ones such as acute pulmonary edema,the low cardiac output syndrome and ARDS.The incidences of widening of the mediastinum,pleural effusion and pulmonary interstitial edema were lower in over 8 d group than those in the other two groups(?