Objective To investigate the clinical significance of BiPAP mechanical ventilation in the treatment of chronic obstructive pulmonary disease(COPD)with type Ⅱ respiratory failure.Methods A total 56 patients suffering from respiratory failure due to exacerbation of COPD were randomly divided into treatment group (BiPAP plus routine therapy)and control group(routine comprehensive therapy).Blood gases,respiratory rates,heart rates,scores of the activity of accessory respiratory muscles,incubation rate,fatality rate were observed.Results In the treatment group,PO2 greatly increased,PCO2 greatly decreased,pH improved significantly,and respiratory rate,heart rate and scores of the activity of accessory respiratory muscles greatly decreased.The incubation rate and the fatality rate were significantly lower in the treatment group than those in the control group(P＜0.05).Conclusion BiPAP mechanical ventilation plus routine therapy on COPD with type Ⅱ respiratory failure can improve the curative effects,lessen respiratory muscle fatigue,and decrease the need for incubation and fatality rate.

Objective To investigate the role of PPAR-γ in the gene expression of T-bet/GATA-3 in Jurkat T cells,and to explore the mechanisms underling this sensitizing effect of the change of TH cell subpopulation group.Methods Jurkat T cells were stimulated with PPAR-γ agonist pioglitazone.TH cell related cytokine IFN-γ and IL-10 was detected by ELISA,and the expression of transcription factors(T-bet and GATA-3)mRNA was detected by RT-PCR.To prove the PPAR-γ-dependent effect.the PPAR-γ-specific antagonist GW9662 was used.Results Stimulated with agonist PPAR-γpioglitazone.the concentration of IFN-γ and IL-10 and the expression of transcription factor T-bet and GATA-3 mRNA were both significantlY decreased in Jurkat T cells obviously,and these actions were dependent on the time and the concentrations of pioglitazone.Added with antagonist GW9662 at the same time,such inhibitory actions of IFN-γ and T-bet expression were recovered.but not IL-10 and GATA-3.Conclusion Pioglitazone can inhibite T cells proliferation and their secretion of cytokines.Pioglitazone can inhibit TH1 cells from secreting cytokines,and it is a PPAR-γ-dependent effect related to T-bet.The inhibition on TH2 is not a PPAR-γ-dependent effect and it is GATA-3 related.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with pachyonychia congenita (PC). METHODS: With informed consent obtained, peripheral blood samples were taken from the pedigree. Genomic DNA was extracted with a phenol/chloroform method. Based on the clinical manifestation of the patients, candidate genes for PC were selected. Potential mutation was screened by PCR and Sanger sequencing. Suspected mutation was verified in other family members by PCR-high resolution melting (HRM) analysis. Haplotype analysis using microsatellite markers was also carried out to determine the founder of the mutation. RESULTS: A heterozygous c.275A>G (Asn92Ser) mutation was discovered in exon 1 of the KRT17 gene in the proband. PCR-HRM analysis showed that all affected members were heterozygous carriers of the mutation. The same mutation was found in none of the unaffected members. Haplotype analysis and sequencing indicated the mother of the proband to be the founder. CONCLUSION The c.275A>G (Asn92Ser) mutation of the KRT17 gene probably underlies the disease in this pedigree. Above finding has facilitated genetic counseling and prenatal diagnosis for this pedigree.
Asian Continental Ancestry Group ; Humans ; Keratin-17 ; genetics ; Mutation ; Pachyonychia Congenita ; genetics ; Pedigree ; Polymerase Chain Reaction

Ubiquitin (Ub) and ubiquitin-like (Ubl) pathways are critical post-translational modifications that determine whether functional proteins are degraded or activated/inactivated. To date, >600 associated enzymes have been reported that comprise a hierarchical task network (e.g., E1-E2-E3 cascade enzymatic reaction and deubiquitination) to modulate substrates, including enormous oncoproteins and tumor-suppressive proteins. Several strategies, such as classical biochemical approaches, multiomics, and clinical sample analysis, were combined to elucidate the functional relations between these enzymes and tumors. In this regard, the fundamental advances and follow-on drug discoveries have been crucial in providing vital information concerning contemporary translational efforts to tailor individualized treatment by targeting Ub and Ubl pathways. Correspondingly, emphasizing the current progress of Ub-related pathways as therapeutic targets in cancer is deemed essential. In the present review, we summarize and discuss the functions, clinical significance, and regulatory mechanisms of Ub and Ubl pathways in tumorigenesis as well as the current progress of small-molecular drug discovery. In particular, multiomics analyses were integrated to delineate the complexity of Ub and Ubl modifications for cancer therapy. The present review will provide a focused and up-to-date overview for the researchers to pursue further studies regarding the Ub and Ubl pathways targeted anticancer strategies.

Objective: To explore the genetic basis for a Chinese pedigree affected with pachyonychia congenita (PC). Methods: With informed consent obtained, peripheral blood samples were taken from the pedigree. Genomic DNA was extracted with a phenol/chloroform method. Based on the clinical manifestation of the patients, candidate genes for PC were selected. Potential mutation was screened by PCR and Sanger sequencing. Suspected mutation was verified in other family members by PCR-high resolution melting (HRM) analysis. Haplotype analysis using microsatellite markers was also carried out to determine the founder of the mutation. Results: A heterozygous c. 275A>G (Asn92Ser) mutation was discovered in exon 1 of the KRT17 gene in the proband. PCR-HRM analysis showed that all affected members were heterozygous carriers of the mutation. The same mutation was found in none of the unaffected members. Haplotype analysis and sequencing indicated the mother of the proband to be the founder. Conclusion The c. 275A>G (Asn92Ser) mutation of the KRT17 gene probably underlies the disease in this pedigree. Above finding has facilitated genetic counseling and prenatal diagnosis for this pedigree.