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Hippo signal pathway is one of the main signal pathways regulating cell proliferation and apoptosis in multicellular animals, which plays a vital role in the maintenance of tissue homeostasis and the regulation of organ growth. Most mammals have limited regenerative potential, and recent studies have shown that Hippo signal pathway is critical in the regeneration of various tissues and organs. The role of Hippo signaling pathway in organ regeneration and the research progress of related targets were introduced, the mechanism of Hippo signaling pathway promoting regeneration analyzes were aralyzed in this review, which provide theoretical reference for the treatment of diseases related to organ regeneration.
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OBJECTIVE@#To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS).@*METHODS@#Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls.@*RESULTS@#The patient was found to harbor a heterozygous c.420C>G (p.Asn140Lys) variant of the SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases.@*CONCLUSION@#The c.420C>G variant of the SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.
Subject(s)
Humans , Amyotrophic Lateral Sclerosis/genetics , China , Heterozygote , Superoxide Dismutase-1/genetics , Exome SequencingABSTRACT
OBJECTIVE@#To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly.@*METHODS@#The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree.@*RESULTS@#The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5).@*CONCLUSION@#The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.
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Female , Humans , China , Mutation , Pedigree , Polydactyly/genetics , Thumb , Exome SequencingABSTRACT
OBJECTIVE@#To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function.@*METHODS@#Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization.@*RESULTS@#The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene.@*CONCLUSION@#The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.
Subject(s)
Female , Humans , Male , DNA Mutational Analysis , Frameshift Mutation , HEK293 Cells , HeLa Cells , Pedigree , Polycystic Kidney, Autosomal Dominant/physiopathology , Protein Kinases/genetics , Protein Transport/genetics , Exome SequencingABSTRACT
Although the combination of surgery, radiotherapy and chemotherapy is the main methods of cancer treatment, it still fails to solve certain tumors, especially metastatic tumors. With the in-depth study of tumorigenesis and development mechanism, and the exploration and clinical application of tumor immunotherapy, the survival period of patients with malignant tumors has been significantly prolonged. Tumor immunotherapy has become an effective anti-tumor method by activating the body′s own immune system to achieve tumor suppression. The combination of chemotherapy and immunotherapy has a significant effect and has become a feasible solution for cancer treatment. The rationally designed nanomedicines can effectively combine chemical drugs and immunological preparations, and have become an effective delivery carrier basis and treatment means for clinically targeting tumor tissues, synergistic immune mechanisms to kill tumor cells, and treating tumors. In this paper, the types of multifunctional nanomedicines used in chemotherapy and various immunotherapies in recent years and their advantages in cancer therapy were reviewed.
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OBJECTIVE： To study the relationships of polymorphism of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus with drug concentration of methotrexate （MTX） and high-dose MTX （HD-MTX）-induced ADR in acute lymphoblastic leukemia （ALL） children. METHODS： From Oct. 2015 to Sept. 2018， 70 ALL hospitalized children of Han nationality in Sichuan area who received HD-MTX treatment and were in consolidation chemotherapy were selected retrospectively from Sichuan People’s Hospital. The blood concentration of MTX at 48 and 72 hours after administration was measured by EMIT. The genetic typing of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus were detected with real-time PCR. The relationships of the polymorphism of MTRR gene and SLCO1B1 gene with MTX blood concentration [dose-corrected concentration （c48 h/D，48 h）， the proportion of children with different concentration of MTX （≤0.1， ＞0.1 μmol/L）] and ADR （such as myelosuppression， liver function damage， gastrointestinal response， mucosal damage， rash， etc.） were analyzed. Binary Logistic regression analysis for the correlation of ADR with different influencing factors （gene polymor- phism， blood concentration of MTX， immunophenotyping， body mass index， etc.） was carried out by Wald method. RESULTS： Totally 31， 32， 7 children with MTRR gene AA， AG and GG genotype， while 23， 37， 10 children with SLCO1B1 gene TT， TC and CC genotype were detected. The distribution of each genotype in 70 children conformed to Hardy-Weinberg equilibrium （P＞0.05）. There was no significant difference in c48 h/D（48 h） of children and the proportion of children with different concentration of MTX （72 h） among difterent genotypes of MTRR and SLCO1B1 gene （P＞0.05）. There was statistical significance in the incidence of liver function injury in children with different genotypes of MTRR gene （P＜0.05）， and the AA genotype was significantly higher than the AG+GG genotype （P＜0.05）. There was no correlation of MTRR gene polymorphism with the incidence of other ADR， neither SLCO1B1 gene polymorphism with the incidence of ADR （P＞0.05）. The results of Binary Logistic regression analysis showed that liver function damage in ALL children was related to the gene polymorphism of MTRR； gastrointestinal reaction was related to whether the plasma concentration was more than 0.1 μmol/L at 72 h； mucosal damage was related to the immune type and BMI of children； the occurrence of skin allergy was correlated with body weight of children（P＜0.05）. CONCLUSIONS： Gene polymorphism of MTRR rs1801394 locus may associated with the occurrence of HD-HTX-induced liver function injury in ALL children， but its polymorphism and gene polymorphism of SLCO1B1 rs11045879 locus are not related to MTX blood concentration in ALL children.
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Although the combination of surgery, radiotherapy and chemotherapy is the main methods of cancer treatment, it still fails to solve certain tumors, especially metastatic tumors. With the in-depth study of tumorigenesis and development mechanism, and the exploration and clinical application of tumor immunotherapy, the survival period of patients with malignant tumors has been significantly prolonged. Tumor immunotherapy has become an effective anti-tumor method by activating the body's own immune system to achieve tumor suppression. The combination of chemotherapy and immunotherapy has a significant effect and has become a feasible solution for cancer treatment. The rationally designed nanomedicines can effectively combine chemical drugs and immunological preparations, and have become an effective delivery carrier basis and treatment means for clinically targeting tumor tissues, synergistic immune mechanisms to kill tumor cells, and treating tumors. In this paper, the types of multifunctional nanomedicines used in chemotherapy and various immunotherapies in recent years and their advantages in cancer therapy were reviewed.
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Objective To study the effect of olanzapine combined with repetitive transcranial magnetic stimulation(rTMS) in the treatment of phonism dominated schizophrenia.Methods From August 2015 to November 2016,112 patients with phonism based schizophrenia in Ningbo Kangning Hospital were selected in the research . According to the different treatment ,the patients were divided into observation group and control group ,with 56 cases in each group.The observation group was treated with olanzapine combined with rTMS chemotherapy ,the control group was treated with olanzapine.Before and after treatment,the positive and negative symptom scale ( PANSS) score, Wisconsin Card Sorting Test ( WCST) score of the two groups were observed.The clinical efficacy was compared between the two groups.Results Before treatment,there were no statistically significant differences in PANSS score and WCST score between the two groups ( all P＞0.05).After treatment for 1 week,2 weeks,4 weeks,the PANSS scores of the two groups were significantly lower than those before treatment (F＝170.710,106.028,28.530,30.328, 25.806,10.832,203.342,372.253,all P＜0.05).The PANSS scores decreased more significantly in the observation group.After treatment for 1,2,4 weeks,the scores of positive symptoms in the observation group were (25.95 ±3.50)points, (24.72 ±4.50)points and(16.51 ±2.70)points,respectively,which were significantly lower than those in the control group[(27.27 ±2.03)points,(27.80 ±5.37)points,(19.53 ±3.07)points](t＝2.441,3.290,5.528,all P＜0.05).After treatment for 1 week,2 weeks,4 weeks,the continuous response scores in the observation group were (45.62 ±5.41)points,(44.69 ±4.91) points,(35.89 ±3.30) points,respectively,which were significantly lower than those in the control group[(50.61 ±5.35)points,(46.80 ±5.14)points,(42.70 ±5.04)points](t＝4.908, 2.221,8.459,all P＜0.05).The scores of continuous errors in the observation group were (49.47 ±4.59) points, (46.53 ±6.05) points and (36.35 ±5.18) points,respectively,which were lower than those in the control group [(83.1 ±6.58)points,(81.85 ±6.70)points and (76.86 ±76.86)points](t＝31.369,29.279,38.464,all P＜0.05).After treatment for 1 week,2 weeks,the classification scores in the observation group were (4.21 ±2.03) points and (5.35 ±2.23) points,respectively,which were significantly higher than those in the control group [(3.35 ±1.24)points and (3.95 ±1.24)points] (t＝2.705,4.106,all P＜0.05).The effective rate was 91.0%in the observation group ,which was 89.2%in the control group,there was no statistically significant difference (χ2＝0.022,P＞0.05).Conclusion Olanzapine combined with rTMS is effective in the treatment of schizophrenia ,and olanzapine combined with rTMS is more effective in improving the cognitive ability of patients than olanzapine alone .
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Chuangxinmycin is an antibiotic isolated from CPCC 200056 in the 1970s with a novel indole-dihydrothiopyran heterocyclic skeleton. Chuangxinmycin showed antibacterial activity and efficacy in mouse infection models as well as preliminary clinical trials. But the biosynthetic pathway of chuangxinmycin has been obscure since its discovery. Herein, we report the identification of a stretch of DNA from the genome of CPCC 200056 that encodes genes for biosynthesis of chuangxinmycin by bioinformatics analysis. The designated cluster was then confirmed to be responsible for chuangxinmycin biosynthesis by direct cloning and heterologous expressing in M1146. The cytochrome P450 CxnD was verified to be involved in the dihydrothiopyran ring closure reaction by the identification of seco-chuangxinmycin in M1146 harboring the gene cluster with an inactivated . Based on these results, a plausible biosynthetic pathway for chuangxinmycin biosynthesis was proposed, by hijacking the primary sulfur transfer system for sulfur incorporation. The identification of the biosynthetic gene cluster of chuangxinmycin paves the way for elucidating the detail biochemical machinery for chuangxinmycin biosynthesis, and provides the basis for the generation of novel chuangxinmycin derivatives by means of combinatorial biosynthesis and synthetic biology.
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Objectives This study aimed to understand the attitude of medical students at the undergraduate level towards the learning of first-aid skills and knowledge as well as pre-hospital first-aid services.Furthermore,this study helped to design a more effective strategy of first-aid education in medical schools.Methods A questionnaire survey was conducted among 1219 undergraduates in medical university,using stratified and cluster proportion sampling method.Results When an accident was met,81.26％ of the undergraduates would voluntarily offer pre-hospital first-aid assistance;77.76％ students had studied first aid knowledge through various channels.However,most students did not have a systematic comprehension of first-aid knowledge and skills.Conclusion Undergraduates in medical university have a positive attitude to offering pre-hospital first-aid assistance;however,the majority of students lack the ability to provide correct and effective assistance.Therefore,medicinal university needs to provide the students with more effective first-aid education.
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Objective: To evaluate the long-term efifciency of percutaneous transluminal septal myocardial ablation (PTSMA) for treating the patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: A total of 66/94 (70.2%) HOCM patients received PTSMA in Shenyang PLA general hospital from 2001-10 to 2012-10 were retrospectively studied. The left ventricular out lfow gradient (LVOFG) was measured at before and after the operation, ECG and echocardiography were examined at 1 month, 6 months and 1 year after operation, and then examined once per year for (63.8±28.5) months. Results: There were 26 patients lost contact during follow-up period, 40 returned to routine clinical check-up and 2 patients died thereafter, 1 because of sudden death and 1 because of cerebral bleeding. The pre-operative average LVOTG was (102.7 ± 47.5) mmHg, compared with the values at 6 months post-operation and long term (>6 months) after operation (33.9 ± 30.2) mmHg and (29.7 ± 25.4) mmHg,P Conclusion: PTSMA may reduce LVOTG, IVS thickness and improve the clinical symptoms in HOCM patients, the long-term efifcacy is reliable.
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In this paper, a new method combining wavelet packet transform and multivariate multiscale entropy for the classification of epilepsy EEG signals is introduced. Firstly, the original EEG signals are decomposed at multi-scales with the wavelet packet transform, and the wavelet packet coefficients of the required frequency bands are extracted. Secondly, the wavelet packet coefficients are processed with multivariate multiscale entropy algorithm. Finally, the EEG data are classified by support vector machines (SVM). The experimental results on the international public Bonn epilepsy EEG dataset show that the proposed method can efficiently extract epileptic features and the accuracy of classification result is satisfactory.
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Humans , Electroencephalography , Classification , Methods , Entropy , Epilepsy , Diagnosis , Signal Processing, Computer-Assisted , Wavelet AnalysisABSTRACT
The present paper is aimed to discuss the influence of three different ways on modification of aluminum borate whiskers (AlBw) and on flexural properties of dental composite resins. In Group A, AlBw and silicon dioxide (SiO2) nanoparticles were thermally fused directly under certain processes. In Group B, Si-O network was formed on the surface of AlBw via the sol-gel process of tetraethoxysilane, then thermally fused with SiO2 nanoparticles to form AlBw-SiO2 compound as inorganic fillers. In Group C, SiO2 nanoparticles were repaired by sol-gel method of tetraethoxysilane under certain processes, and were deposited in the surface of AlBw. The mixtures were fused with high temperature sintering method. The effects of the surface morphology of AlBw with different ways were characterized by TEM and SEM. Then the mixtures were polymerized with resin matrix after surface siliconization and their flexural strength and Young's modulus were determined. SEM was used to examine specimen fracture surfaces. The results showed that the flexural properties of dental composite resins were significantly improved after whiskers were modified. Different methods produce different effects. Flexural strength of the Group A is (95.28 +/- 4.53) MPa. The results of TEM and SEM revealed that the aggregation was obvious between AlBw and SiO2 nanoparticles. Flexural strength of the Group B was (123.14 +/- 17.37) MPa. The results of TEM and SEM revealed that the dispersity was improved but SiO2 nanoparticles also reunited. AlBw were modified with nanometer-size SiO2 particles which were prepared by sol-gel method based on tetraethyl orthosioate (TEOS), the flexural properties of a new type of dental composite resins was (130.29 +/- 8.38) MPa. The results of TEM and SEM revealed that better dispersion between AlBw and SiO2 nanoparticles occurred. The SiO2 nanoparticles were fused and attached onto the surface of AlBw uniformly.
Subject(s)
Acrylic Resins , Chemistry , Aluminum Compounds , Chemistry , Boron Compounds , Chemistry , Composite Resins , Chemistry , Elastic Modulus , Elasticity , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nanoparticles , Chemistry , Phase Transition , Polyurethanes , Chemistry , Silanes , Chemistry , Silicon Dioxide , Chemistry , Stress, Mechanical , Surface PropertiesABSTRACT
OBJECTIVE@#To investigate the effect of human bone morphogenetic protein (hBMPs) 2/3/6 and 12 on osteosarcoma cell UMR106.@*METHODS@#Adenovirus-BMP2/3/6 and 12 (AdBMP2/3/6 and12) were used to treat the cell line. Their proliferation, apoptosis, and transmigration were detected by Trypan blue exclusion test, TdT-mediated biotinylated-dUTP nick end labeling (TUNEL), acridine orange-ethidium bromide (AO/EB) double fluorescent dye staining, and transwell-room test, respectively. The alkaline phosphatase (ALP) activity was detected to reflect the differentiation of tumors.@*RESULTS@#Compared with the control groups, the cell survival rate of the experimental groups treated with AdBMP2/3/6 and 12 showed a significant time-dependent decrease (P<0.01). The apoptosis indexes were increased significantly (P<0.01) and the results from TUNEL and AO/EB method were consistent. The cell numbers of transmembrane significantly decreased at 24,48, and 72 h (P<0.01). AdBMP2/3/6 and 12 treatment enhanced the activity of ALP activity from day 3 and this effect might still be observed up to day 9 of the treatment (P<0.01).@*CONCLUSION@#hBMPs2/3/6 and 12 can inhibit the proliferation and transmigration, and induce their apoptosis and differentiation in osteosarcoma cell line UMR106.
Subject(s)
Humans , Adenoviridae , Genetics , Metabolism , Apoptosis , Bone Morphogenetic Protein 2 , Pharmacology , Bone Morphogenetic Protein 3 , Pharmacology , Bone Morphogenetic Protein 6 , Pharmacology , Bone Morphogenetic Proteins , Pharmacology , Bone Neoplasms , Pathology , Cell Line, Tumor , Cell Transformation, Neoplastic , Growth Differentiation Factors , Pharmacology , Osteosarcoma , Pathology , Recombinant Proteins , PharmacologyABSTRACT
Objective The biological effects of BMP3 on osteosarcoma were investigated by treating human osteosarcoma cell lines MG63,and U2OS with human BMP3(hBMP3).Methods Osteosarcoma cells in experimental groups were respectively treated with AdBMP-3 and rhBMP3-CM,control groups with AdGFP and rGFP-CM,the blank group with neither.Their ability of proliferation,apoptosis,transmigration and differentiation were respectively detected by trypan blue exclusion test,terminal deoynucleotidyl transferase mediated dUTP nick end labeling(TUNEL) and acridine orange-ethidium bromide fluorescent stain(AO/EB),transwell-room and alkaline phosphatase(ALP) activity reagent kit.Results(1) All the indexes detected were not significantly different between two control groups.(2) Compared with control groups,the cell survival rate showed a significant decrease in experimental groups.(3) The apoptosis indexes increased.(4)The number of trans-membrane cell decreased.(5)The activity of alkaline phosphatase increased after treatment with AdBMP3 and rhBMP-3 for 3 days in MG63,5 days in U2OS.Conclusion hBMP3 inhibit osteosarcoma cells growth and promote bone formation.
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@#ObjectiveTo study the application of retinal tomography in primary open angle glaucoma diagnosis.MethodsThe differences between POAG, high myopia with suspected glaucoma and normal volunteers on the rim area, rim volume and the thickness of retinal nerve fiber layer (RNFL) thickness in quadrants under Heideberg retinal tomography-Ⅱ(HRT-Ⅱ) were analyzed.ResultsIn the cases of POAG and high myopia with suspected glaucoma, the values of rim area, rim volume and RNFL thickness were significantly lower than that in normal group.ConclusionRetinal tomography can be used in the diagnosis of POAG.
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@#ObjectiveTo study the assistant therapic effect of the Botulinum toxin A (BTA) on tiptoe after cerebral palsy(CP).MethodsMulti point injection of BAT into the musculus gastrocnemius combined with the rehabilitate therapy was used on 35 children(39 feet)with tiptoe after CP.The therapeutic effect was evaluated after a month.ResultsThe efficiency rate is 25.6%,the slight efficiency rate is 71.8%,the ineffective rate is 2.6%.There is no toxic or side effect was observed.Conclusions The BTA can relieve spasm of musculature and redress abnormality from convulsing of musculature.