Eighty-two newly-diagnosed type 2 diabetic patients with poor glycemic control were treated by mitiglinide calcium for 16 weeks.Plasma fibroblast growth factor-21 ( FGF-21 ) level were evaluated.The relationship of plasma FGF-21 levels with body mass index,body fat,waist-to-hip ratio,lipid,blood glucose,HbA1c,and free fatty-acid were analyzed.Plasma FGF-21 was decreased significantly by treatment with mitiglinide calcium in type 2 diabetic patients,and it may play a role in the pathogenesis of type 2 diabetes mellitus.

OBJECTIVETo investigate the expression feature of peroxiredoxin III in cervical lesions and to further understand the mechanism for cervical cancer development/progression.

METHODSExpression of peroxiredoxin III was immunohistochemically detected in cervical cancer. In addition, cervical epithelia were transfected with recombinant adeno-associated virus vector containing human papillomavirus 16 E6/E7 and peroxiredoxin III expression was detected by quantitative real time PCR and Western blotting.

RESULTSPeroxiredoxin III was significantly up-regulated in cervical cancer tissues. Nevertheless, expression of peroxiredoxin III remained unchanged in cervical epithelial cells after transfection.

CONCLUSIONIt seems that Prx III is not related to cervical cancer initiation. Up-regulation of peroxiredoxin III in cervical cancer might be an active response to oxidative stress in malignant cells, which protects against oxidatiton-induced apoptosis.

Cervix Uteri ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Human papillomavirus 16 ; genetics ; metabolism ; Humans ; Middle Aged ; Oncogene Proteins, Viral ; genetics ; metabolism ; Papillomavirus E7 Proteins ; genetics ; metabolism ; Peroxiredoxins ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Up-Regulation ; Uterine Cervical Neoplasms ; genetics ; metabolism ; virology

To compare two different methods for extracting genomic DNA from cord blood and to evaluate their applications for HLA genotyping, the genomic DNA from 72 samples was extracted by guanidine hydrochloride (Gu * HCl) and modified guanidine hydrochloride, the DNA yield and purity were evaluated by spectrophotometry and detected by PCR with sequence-specific primers. The result showed that the genomic DNA was successfully isolated from whole blood by both methods. The modified Gu * HCl method used was better than Gu * HCl method as the modified method produces better quality of DNA and less ambiguous bands in PCR. It is concluded that modified Gu * HCl method has the advantages of low-cost, simple operation, high quality output and clear positive bands in HLA-genotyping, the modified method is optimal for extracting DNA from multiple samples of cord blood bank.
DNA ; blood ; isolation & purification ; Fetal Blood ; chemistry ; Genotype ; Guanidine ; HLA Antigens ; genetics ; Humans ; Polymerase Chain Reaction ; methods

OBJECTIVETo analyze alterations in the gene expression profiles of Velcade-treated K562 cells using bioinformatics methods.

METHODSThe total RNAs of Velcade-treated and control K562 cells were amplified and labeled with fluorescent dyes. The labeled RNAs were hybridized to Agilent Human 1A Microarray, and the raw expression data were processed with Agilent Feature Extraction Software. GeneSifter and GATHER were used for data analysis of the differentially expressed genes to perform gene ontology classification, KEGG pathway analysis, functional protein association network construction and literature mining.

RESULTSTotally 228 differentially expressed genes were identified in the Velcade-treated K562 cells. including 84 up-regulated and 144 down-regulated genes. Chymase 1 gene had the greatest down-regulation by 10.80 folds (log ratio), and interferon alpha-21 gene was also down-regulated by 2.31 folds. Gene ontology classification suggested enhanced aging and leukocyte activity. KEGG pathway analysis showed significant impact of Velcade on JAK-STAT signaling pathway, cytotoxicity mediated by natural killer cells, and antigen processing and presentation pathways. Protein-protein interaction analysis revealed that ubiquitin-dependent protein catabolism, antigen presentation and immune response, as well as JAK-STAT signaling pathway were the major elements of the protein network. Literature mining showed that the differentially expressed genes were strongly associated with terms such as leukemia, apoptosis, cell cycle, proteasome, inhibitor, aging and IkappaB, etc.

CONCLUSIONSVelcade may inhibit the cell survival pathways such as NF-kappaB and JAK-STAT signaling pathways to enhance the cytotoxicity and inducing tumor cell apoptosis. Velcade might also be involved in antigen processing and presentation, immune response and inflammation. Chymase 1 gene is probably the key target of Velcade.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Chymases ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; K562 Cells ; Oligonucleotide Array Sequence Analysis ; methods ; Pyrazines ; pharmacology

Nine mutants (P2M1-9) were obtained using PCR with 5-BU based on DNA template (P2Y) encoding the active region of Parasporin-2. Mutant proteins were purified after expressing in E. coli BL21 cells, followed by assayed against hepatoma cells and normal liver cells by MTT. They showed diverse anti-hepatoma activities, in which two mutant proteins, P2M1 and P2M8, exhibited high cytotoxicity against hepatoma cell lines SMMC7721 and Be17402, meanwhile leaving normal liver cells Chang-liver unaffected. Structural comparison among P2Y, P2M1 and P2M8 showed that the length of beta-sheet or beta-fold, and the amount of alpha helix greatly affected the anti-hepatoma activity of Parasporin-2. Results based on amino acid alignment, molecular docking between P2Y, P2M1 or P2M8 and receptor, and mimic mutation demonstrated that amino acid residues at the sites of 52, 56, 58 and 208 on P2Y, especially the aromatic amino acids such as Trp, Phe, and Tyr were involved in the interactions.
Amino Acid Sequence ; Amino Acids, Aromatic ; biosynthesis ; genetics ; pharmacology ; Antineoplastic Agents ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Endotoxins ; chemistry ; pharmacology ; Escherichia coli ; genetics ; metabolism ; Humans ; Liver Neoplasms ; pathology ; Molecular Sequence Data ; Mutant Proteins ; pharmacology ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology

BACKGROUND: Ventilation dysfunction caused by bronchomalacia induced bronchostenosis following high-risk heart transplantation is an acute clinical disease, which seriously impairs the function of transplant heart. The case of emergency bronchial stent placement following heart transplantation with high-risk multi-complication has not been reported yet.OBJECTIVE: To investigate the curative effect of emergency stent placement for worse left main bronchial malacia, stenosis and collapse following orthotopic heart allotransplantation.DESIGN: A case analysis.SETTINGS: National Ministry of Health Transplantation Engineering and Technical Research Center, the Third Xiangya Hospital, Central South University; Department of Cardiosurgery, Zhongshan Hospital affiliated to Xiamen University.PARTICIPANTS: An 18-year-old female patient with dilated cardiomyopathy accompanied by moderate to severe pulmonary artery hypertension, who sequentially carried out orthotopic heart allotransplantation, was selected from the Department of Cardiosurgery, Zhongshan Hospital affiliated to Xiamen University in April, 2004. She had suffered from dilated cardiomyopathy for 15 years, and the mean pulmonary artery pressure (MPAP) was 50-51 mm Hg, she was also accompanied by left main bronchial malacia, stenosis and collapse, mixed (mainly central-) sleep apnea syndrome, left inferior pulmonary sequestration, right emphysema, and rheumatoid arthritis for half a year.METHODS: After heart transplantation, bronchus inflammation, congested edema aggravated the severity of bronchial malacia, stenosis and collapse, tenosis reduced to 4/5, and led to obstructive type of ventilation, and the patient was also accompanied by supraventricular tachycardia, ventricular extrasystole, and hypofunction of transplant cardiac systolic function (peak E＜peak A, ejection fraction reduced to 40%, inharmonious motion of ventricular wall). Attempted with inotropic agents and ventilator/support were not relieved, which resulted in the aggravation of illness. In order to improve the post-transplant cardiac function, to relieve bronchial collapse and stenosis, and correct the obstructive type of ventilation, an emergency bronchial stent placement surgery was carried out on the sixth day after heart transplantation. Under monitoring of electrocardiogram (EGG) and percutaneaous oxygen saturation (SpO2), patient was awake and in supine to relieve left main bronchial stenosis with a nickel-titanium shape memory alloy stent (Diameter: 12 mm; length: 20 mm) by D20 fiberoptic bronchoscope. Fibrobronchoscopy was used to observe the proximal end of bronchostenosis and set the proximate location mark by using video fluoroscopy; the patency of distal end was explored by stricture, and set the distal location mark; guidewire was inserted into working path of bronchofibroscope and led through the stricture; then loaded the Ni-Ti stent on a special placement apparatus, and led in bronchial stent implantation apparatus along guidewire. When targeting well, the stent was slowly released and adjusted properly. When it was completely released, the stent implantation apparatus was drawn out. Bronchofibroscope was performed postoperatively to observe the adherence of stent; immediately photographed to observe its unfolding. Synchronized intermittent mandatory ventilation (SIMV) was given postoperatively as supportive treatment.MAIN OUTCOME MEASURES: Ameliorations of the cardiac and pulmonary functions of the patient.RESULTS: ①Carbon dioxide retention and hypercapnia were remarkably improved as compared with those preoperatively; hypertensive pulmonary vascular disease was alleviated gradually, and MPAP reduced to 30 mm Hg. One week later, re-examination of bronchofibroscopy was carried out, and the results showed that bronchi of left upper lobe, lingual lobe as well as left lower lobe could be seen distinctly, mucous membrane had slightly congested edema, and lumens were unobstructed.②Supraventricular tachycardia and premature ventricualr contraction disappeared, and the transplant cardiac function recovered well (peak E ＞ peak A, ejection fraction 70%, FS41%), and the heart rate fluctuated at 100-110 beats per minute. ③The chest-radiography and CT postoperatively indicated the relief of left main bronchial stenosis. When the ventilation function of the patient was improved, the parameters of breathing machine were reduced gradually, and replaced by low-flow oxygen. There was no recurrence of obstructive ventilatory disorder. The sleep apnea syndrome of the patient was moderated.CONCLUSION: Emergency treatment with stent placement for bronchial malacia, stenosis and collapse occurring after orthotopic heart allotransplantation cAN improve ventilation dysfunction caused by bronchial malacia and stenosis,and increase the survival rate of heart transplantation.

Most important international guidelines recommend the use of CHA 2 DS 2 -VASc and HASBLED scores for stroke and bleeding risk assessments in atrial fibrillation (AF) patients, respectively. The 2020 AF guidelines of European Society of Cardiology have revised the definition of “C: congestive heart failure (HF)” component, and now patients with either HF with reduced ejection fraction or preserved ejection fraction should be assigned 1 point.Hypertrophic cardiomyopathy was also included. Besides, the revised “V: vascular diseases” component included both prior myocardial infarction and “angiographically significant coronary artery disease”. It is important to understand that the stroke and bleeding risks of AF patients were not static and should be re-assessed regularly. A high HAS-BLED score itself should not be the only reason to withhold or discontinue oral anticoagulants, but remind physicians for the corrections of modifiable bleeding risk factors and more regular follow up. In the future, the AF duration and left atrial function may play an important role for personalized evaluation of individual stroke risk while more studies are necessary.

Diffusion tensor imaging (DTI) can be used to characterize the orientation of water diffusion, and track white matter fiber bundles. The decrease of fractional anisotropy after stroke indicates impairment of structural integrity of fibers, even Wallerian degeneration if serious; in another hand, the increase of fractional anisotropy relates to the more recovery of motor function. The affected/unaffected ratios of fractional anisotropy are more suitable for predicting motor function recovery after stroke. The changes of corticospinal tract in diffusion tensor tractography can also predict the motor outcome in stroke patients.

A practical approach to the synthesis of the A, B and C-ring subunit of cyclopamine has been developed. This synthetic tactic highlights the utility of mandelate acetal-mediated resolution of the fused ring ketone (±)-4 and IBX-mediated oxidation cascades from 12 to 9. The availability of advanced intermediates from enantiomerically pure (+)-4 and 2 could provide efficient access to biologically active and structurally diverse C-nor-D-homo-steroidal alkaloids such as cyclopamine.
Chemistry Techniques, Synthetic ; methods ; Molecular Structure ; Organic Chemistry Phenomena ; Stereoisomerism ; Steroids ; chemistry ; Veratrum Alkaloids ; chemical synthesis ; chemistry

Most important international guidelines recommend the use of CHA 2 DS 2 -VASc and HASBLED scores for stroke and bleeding risk assessments in atrial fibrillation (AF) patients, respectively. The 2020 AF guidelines of European Society of Cardiology have revised the definition of “C: congestive heart failure (HF)” component, and now patients with either HF with reduced ejection fraction or preserved ejection fraction should be assigned 1 point.Hypertrophic cardiomyopathy was also included. Besides, the revised “V: vascular diseases” component included both prior myocardial infarction and “angiographically significant coronary artery disease”. It is important to understand that the stroke and bleeding risks of AF patients were not static and should be re-assessed regularly. A high HAS-BLED score itself should not be the only reason to withhold or discontinue oral anticoagulants, but remind physicians for the corrections of modifiable bleeding risk factors and more regular follow up. In the future, the AF duration and left atrial function may play an important role for personalized evaluation of individual stroke risk while more studies are necessary.