Toll-like receptor 4 (TLR4) recognizes pathogen ligands and mediates signaling to initiate innate and adaptive immune responses. In this experiment, a 316 bp and 382 bp fragments of TLR4 gene named T4CRBR1 and T4CRB...Toll-like receptor 4 (TLR4) recognizes pathogen ligands and mediates signaling to initiate innate and adaptive immune responses. In this experiment, a 316 bp and 382 bp fragments of TLR4 gene named T4CRBR1 and T4CRBR2, of Chinese Holstein, Sanhe cattle, and Chinese Simmental was amplified by polymerase chain reaction (PCR), respectively. The genetic polymorphisms in the three populations were detected by Single-Strand Conformational Polymorphism (SSCP) in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results showed that both alleles (A and B) of two loci were found in all the three populations and the value of polymorphism information content (PIC) indicated that these were a moderate polymorphism. Statistical results of X^2 test indicated that two polymorphism sites in the three populations fitted with Hardy-Weinberg equilibrium (P 〉 0.05). After sequencing, A-G single nucleotide polymorphism (SNP) was identified at nucleotide 4,525 in intron 1 of TLR4 gene and C-T SNP was identified at nucleotide 1,397 in exon 3 of TLR4 gene. Meanwhile, the effect of polymorphism of TLR4 gene on somatic cell score (SCS) was analyzed, the results indicated that the cattle with allele A in T4CRBR1 showed lower somatic cell score than that of allele B (P 〈 0.05). In short, the allele A might play an important role in mastiffs resistance in bovine.展开更多
Objective To investigate N-myc downstream-regulated gene 2(NDRG2) expression in ovarian cancer cells and its potential usefulness as a diagnostic marker and/or target for therapeutic intervention.Methods Human NDRG2 L...Objective To investigate N-myc downstream-regulated gene 2(NDRG2) expression in ovarian cancer cells and its potential usefulness as a diagnostic marker and/or target for therapeutic intervention.Methods Human NDRG2 L/S gene was obtained by revers-transcription polymerase chain reaction(RT-PCR). Sequence analysis confirmed the identity of NDRG2 L/S gene, which was then inserted into a eukaryotic vector p LNCX2, which was in turn transfected into NDRG2 gene-negative HO-8910 cells. Flow cytometry(FCM) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay were conducted to determine the proliferation rate of HO-8910 cells. Cisplatin resistance of HO-8910 cells transfected with p LNCX2-NDRG2 L/S was evaluated by FCM. Tumors were generated in female nude mice by subcutaneous injection of HO-8910 cells.Results NDRG2 gene was isolated and its expression vector was successfully constructed. NDRG2 expression positively correlated with the proliferation of HO-8910 cells. NDRG2 L/S promoted tumorigenicity in HO-8910 cells.Conclusion The present study identified a novel function of NDRG2 L/S gene and demonstrated its involvement in the promotion of ovarian cancer cell proliferation and enhancement of cisplatin resistance in HO-8910 cells. Future studies are warranted to determine the relationship between NDRG2 upregulation and ovarian cancer progression.展开更多
Baseband design and implementation for micro/pico base stations (mBS) in 5G ultra-dense network (UDN) is studied. Low cost is an essential requirement for mBS baseband in UDN. Digital baseband cost of ASIC/ASIP (...Baseband design and implementation for micro/pico base stations (mBS) in 5G ultra-dense network (UDN) is studied. Low cost is an essential requirement for mBS baseband in UDN. Digital baseband cost of ASIC/ASIP (Application Specific Integrated Circuit / Instruction-set processor) is of the most uncertainty in roBS system. However. the actual costs and hardware feasibility of the baseband are yet unknown to network deployers and researchers. In this paper, we studied the baseband hardware system design and implementation for low-cost roBS. We analyzed popular baseband algorithms and architectures for both full-digital and hybrid beamforming (BF) for UDN. We then proposed feasible chip-level solutions for the baseband with up to 128-antenna BS system, and estimated their implementation cost. Results show that among lull-digital BF algorithms, zero-forcing is a choice of high performance and low cost; for hybrid BF, 4×32 architecture (32 RF chains) provides good reduction in baseband cost with acceptable performance loss, thus it can be a preferable solution under low cost consider- ation. The proposed system planning method can also be used for the design of other related systems.展开更多
4-Hydroxyphenylpyruvic acid (4-HPPA), a kind of α-keto acid, is an intermediate in the metabolism of tyrosine and has a wide range of application in food, pharmaceutical and chemical industry. Using amino acids as ...4-Hydroxyphenylpyruvic acid (4-HPPA), a kind of α-keto acid, is an intermediate in the metabolism of tyrosine and has a wide range of application in food, pharmaceutical and chemical industry. Using amino acids as raw material to prod uce the corresponding α-keto acid is thought to be both economic and efficient. Among the enzymes that convert amino acid to α-keto acid, membrane bound L-amino acid deaminase (mL-AAD), which is anchored to the outer side of the cytomembrane, becomes an ideal enzyme to prepare α-keto acid since there is no cofactors needed and H2O2 production during the reaction. In this study, the mL-AAD from Proteus vulgaris was used to prepare whole-cell catalysts to produce 4-HPPA from L-tyrosine. The secretory efficiency of mL-AAD conducted by its own twin-arginine signal peptide (twin-arginine translocation pathway, Tat) and integrated pelB (the general secretory pathway, Sec)-Tat signal peptide was determined and compared firstly, using two pET systems (pET28a and pET20b). It was found that the Tat pathway (pET28a-mlaad) resulted in higher cell-associated mL-AAD activity and cell biomass, and was more beneficial to prepare biocatalyst. In addition, expression hosts BI21 (DE3) and 0.05 mmol. L- 1 IPTG were found to be suitable for mL-AAD expression. The reaction conditions for mL-AAD were optimized and 72.72 mmol,L 1 4-HPPA was obtained from 100 mmol.L 1 tyrosine in 10 h under the optimized conditions. This bioprocess, which is more eco-friendly and economical than the traditional chemical synthesis ways, has great potential for industrial application.展开更多
AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODS...AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODSTreg and Teff cells from fgl2<sup>-/-</sup>, fgl2<sup>+/+</sup>, and fgl2<sup>Tg</sup> mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1<sup>-/-</sup> mice.RESULTSIn vitro, fgl2<sup>Tg</sup> Treg had enhanced immunosuppressive activity, and fgl2<sup>Tg</sup> Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2<sup>+/+</sup>) into Rag1<sup>-/-</sup> mice produced both clinical and histologic colitis with dense infiltrates of CD3<sup>+</sup> T cells, crypt abscesses and loss of goblet cells. Fgl2<sup>Tg</sup> Treg prevented the development of T cell-induced colitis, whereas fgl2<sup>+/+</sup> and fgl2<sup>-/-</sup> Treg were only partially protective. In mice that received fgl2<sup>Tg</sup> Treg, the ratio of Foxp3<sup>+</sup> to CD3<sup>+</sup> cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2<sup>Tg</sup> mice did not produce colitis.CONCLUSIONHere we show that fgl2<sup>Tg</sup> Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2<sup>Tg</sup> Treg prevent colitis in contrast to fgl2<sup>+/+</sup> Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.展开更多
Atrial fibrillation (AF) is the most common arrhythmia with multi-factorial pathogenesis. A number of studies of genetic epidemiology have assessed the association of G112A (G38S) single nucleotide polymorphisms (SNPs...Atrial fibrillation (AF) is the most common arrhythmia with multi-factorial pathogenesis. A number of studies of genetic epidemiology have assessed the association of G112A (G38S) single nucleotide polymorphisms (SNPs) in Mink gene with AF in different populations. However, the results are inconsistent and inconclusive. We performed a Meta-analysis of the association between G112A polymorphisms of MinK gene and AF to estimate the magnitude of the gene effect. Six case-control studies with a combined 854 cases and 1079 controls were summarized. Subgroups in different races were separately analyzed. Heterogeneity and publication bias were also explored. When all groups were pooled, the individuals with G allele had an over 40% higher risk of AF compared with individuals with the A allele. The GG genotype (versus AA genotype) was found to be significant association with increased AF risk. The significant associations were also found in both dominant and recessive genetic model. For subgroup analysis, the results were consistent with above, except that the pooled OR for Chinese population was not significant in a recessive genetic model. In conclusion, G112A polymorphisms in Mink gene may have an important effect on the pathogenesis of AF. This warrants further investigation in large multi-center studies with precise design.展开更多
AIM: To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in cortico- steroid-free remission. METHODS: Forty-eight ...AIM: To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in cortico- steroid-free remission. METHODS: Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remis- sion was defined as corticosteroid-free plus normaliza- tion of clinical disease activity [CD activity index (CDAI) 〈 150] during follow-up visits based on physician global assessments. A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI 〉 220) and a thera- peutic intervention with CD medication(s), or a hospital- ization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n -- 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment do- main 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBDS) polymorphisms (IGR2060a1 and IGR3081a1) were ana- lyzed in each group. RESULTS: Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no signifcant increase in frequency of the NOD2/CARD15 polymor- phisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060al and IGR3081a1) in either group of patients; those whose disease relapsed rap- idly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of re- sponse remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked dif- ference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years 4- 0.6 years, while those still in remission were at the time of this study, 8.1 years 4- 2.6 years post-discon- tinuation of infliximab, P 〈 0.001. The 8 patients who had lost remission after discontinuing infiiximab had a mean number of 5 infusions (range 3-7), with a mean treatment time of 7.2 mo (range 1.5 mo-15 mo). The mean duration of time from the last infusion of inflix- imab to the time of loss of remission was 382 d (range 20 d-701 d). The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions (range 3-12), with a mean treatment dura- tion of 12 mo (range 3.6 mo-32 too) (P = 0.45 relative to those who lost remission). CONCLUSION: There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sus- tained remission and which will relapse rapidly after stopping infliximab.展开更多
In 2008, two governmental committees presented their conclusions on strengthening the role of the private building sector in building control. In 2011, three new studies were commissioned by the government to address ...In 2008, two governmental committees presented their conclusions on strengthening the role of the private building sector in building control. In 2011, three new studies were commissioned by the government to address perceived problems. One of them was an integral study, executed by ERB (Foundation Expertcentre Regulations in Building), RIGO (Research Institute for Real Estate) and TNO (Research Institute for Applied Technologies), to innovate the whole building regulations system. It led to proposals to redefine responsibility and liability for all parties. This study states that by an effort of yearly £100 million, unnecessary costs up to £l billion can be avoided and a real quality push will take place in the building and real estate markets. The goals to reach are to minimize the administrative burden for the building owner and to enforce the construction industry to build conforming to the regulations. This paper discusses the ERB study and the given proposals. The ERB study demonstrated that a quality push is needed which potential will lead to less costs for building owners. It also shows that proven solutions, part of the regulations, might be of help for all parties involved.展开更多
Advances in clinical and fimdamental research, which have been promoted over last decades have led to a well- established understanding of atrial fibrillation (AF) as an epiphenomenon that despite similar manifestat...Advances in clinical and fimdamental research, which have been promoted over last decades have led to a well- established understanding of atrial fibrillation (AF) as an epiphenomenon that despite similar manifestations may have different underlying mechanisms and thus require in- dividualized treatments. With rare exceptions of AF caused by mutations in genes coding ion channels in pa- tients with structurally normal atria, fibrotic replacement of atrial myocardium remains the comer stone of atrial pa- thology in patients with AF.展开更多
The empirical study uses black swan approach to analyze the performance of South African (ZA) listed property loan stocks (PLSs). Although there are no empirical studies on black swan perspective and performance o...The empirical study uses black swan approach to analyze the performance of South African (ZA) listed property loan stocks (PLSs). Although there are no empirical studies on black swan perspective and performance of listed real estate funds, the study found that there are similar traits of investing in listed real estate funds from emerging markets' perspective and what black swan advocates such as passive investment strategy and non-normality distribution of returns from listed real estate funds. Furthermore, the individual return of each fund was higher the return of the property loan stocks index and the probabilities of all variables confirm that they (variables) are significant when alpha is 10% at confidence level of 90%.展开更多
Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK...Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.展开更多
AIM To evaluate PIK3 CA gene mutational status in Northwest Chinese esophageal squamous cell carcinoma(ESCC) patients, and examine the associations of PIK3 CA gene mutations with clinicopathological characteristics an...AIM To evaluate PIK3 CA gene mutational status in Northwest Chinese esophageal squamous cell carcinoma(ESCC) patients, and examine the associations of PIK3 CA gene mutations with clinicopathological characteristics and clinical outcome.METHODS A total of 210 patients with ESCC who underwent curative resection were enrolled in this study. Pyrosequencing was applied to investigate mutations in exons 9 and 20 of PIK3 CA gene in 210 Northwest Chinese ESCCs. The associations of PIK3 CA gene mutations with clinicopathological characteristics and clinical outcome were examined.RESULTS PIK3 CA gene mutations in exon 9 were detected in 48 cases(22.9%) of a non-biased database of 210 curatively resected Northwest Chinese ESCCs. PIK3 CA gene mutations were not associated with sex, tobacco use, alcohol use, tumor location, stage, or local recurrence. When compared with wild-type PIK3 CA gene cases, patients with PIK3 CA gene mutations in exons 9 experienced significantly better disease-free survival and overall survival rates.CONCLUSION The results of this study suggest that PIK3 CA gene mutations could act as a prognostic biomarker in Northwest Chinese ESCC patients.展开更多
基金This work was supported by the fifteenth "Five Years Key Programs" for Science and Technology Development of China (No. 2002BA518A14)the National High Science and Technology Foundation of China (863) (No. 2002AA242011).
文摘Toll-like receptor 4 (TLR4) recognizes pathogen ligands and mediates signaling to initiate innate and adaptive immune responses. In this experiment, a 316 bp and 382 bp fragments of TLR4 gene named T4CRBR1 and T4CRBR2, of Chinese Holstein, Sanhe cattle, and Chinese Simmental was amplified by polymerase chain reaction (PCR), respectively. The genetic polymorphisms in the three populations were detected by Single-Strand Conformational Polymorphism (SSCP) in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results showed that both alleles (A and B) of two loci were found in all the three populations and the value of polymorphism information content (PIC) indicated that these were a moderate polymorphism. Statistical results of X^2 test indicated that two polymorphism sites in the three populations fitted with Hardy-Weinberg equilibrium (P 〉 0.05). After sequencing, A-G single nucleotide polymorphism (SNP) was identified at nucleotide 4,525 in intron 1 of TLR4 gene and C-T SNP was identified at nucleotide 1,397 in exon 3 of TLR4 gene. Meanwhile, the effect of polymorphism of TLR4 gene on somatic cell score (SCS) was analyzed, the results indicated that the cattle with allele A in T4CRBR1 showed lower somatic cell score than that of allele B (P 〈 0.05). In short, the allele A might play an important role in mastiffs resistance in bovine.
文摘Objective To investigate N-myc downstream-regulated gene 2(NDRG2) expression in ovarian cancer cells and its potential usefulness as a diagnostic marker and/or target for therapeutic intervention.Methods Human NDRG2 L/S gene was obtained by revers-transcription polymerase chain reaction(RT-PCR). Sequence analysis confirmed the identity of NDRG2 L/S gene, which was then inserted into a eukaryotic vector p LNCX2, which was in turn transfected into NDRG2 gene-negative HO-8910 cells. Flow cytometry(FCM) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay were conducted to determine the proliferation rate of HO-8910 cells. Cisplatin resistance of HO-8910 cells transfected with p LNCX2-NDRG2 L/S was evaluated by FCM. Tumors were generated in female nude mice by subcutaneous injection of HO-8910 cells.Results NDRG2 gene was isolated and its expression vector was successfully constructed. NDRG2 expression positively correlated with the proliferation of HO-8910 cells. NDRG2 L/S promoted tumorigenicity in HO-8910 cells.Conclusion The present study identified a novel function of NDRG2 L/S gene and demonstrated its involvement in the promotion of ovarian cancer cell proliferation and enhancement of cisplatin resistance in HO-8910 cells. Future studies are warranted to determine the relationship between NDRG2 upregulation and ovarian cancer progression.
基金supporting from National High Technical Research and Development Program of China(863 program)2014AA01A705 is sincerely acknowledged by authors
文摘Baseband design and implementation for micro/pico base stations (mBS) in 5G ultra-dense network (UDN) is studied. Low cost is an essential requirement for mBS baseband in UDN. Digital baseband cost of ASIC/ASIP (Application Specific Integrated Circuit / Instruction-set processor) is of the most uncertainty in roBS system. However. the actual costs and hardware feasibility of the baseband are yet unknown to network deployers and researchers. In this paper, we studied the baseband hardware system design and implementation for low-cost roBS. We analyzed popular baseband algorithms and architectures for both full-digital and hybrid beamforming (BF) for UDN. We then proposed feasible chip-level solutions for the baseband with up to 128-antenna BS system, and estimated their implementation cost. Results show that among lull-digital BF algorithms, zero-forcing is a choice of high performance and low cost; for hybrid BF, 4×32 architecture (32 RF chains) provides good reduction in baseband cost with acceptable performance loss, thus it can be a preferable solution under low cost consider- ation. The proposed system planning method can also be used for the design of other related systems.
基金Supported by the National Natural Science Foundation of China(31470793,31670804)China Postdoctoral Science Foundation(2016M592003)+1 种基金the Natural Science Foundation of Zhejiang Province(LZ13B060002)the General Scientific Research Project of Zhejiang Provincial Education Department(Y201432760)
文摘4-Hydroxyphenylpyruvic acid (4-HPPA), a kind of α-keto acid, is an intermediate in the metabolism of tyrosine and has a wide range of application in food, pharmaceutical and chemical industry. Using amino acids as raw material to prod uce the corresponding α-keto acid is thought to be both economic and efficient. Among the enzymes that convert amino acid to α-keto acid, membrane bound L-amino acid deaminase (mL-AAD), which is anchored to the outer side of the cytomembrane, becomes an ideal enzyme to prepare α-keto acid since there is no cofactors needed and H2O2 production during the reaction. In this study, the mL-AAD from Proteus vulgaris was used to prepare whole-cell catalysts to produce 4-HPPA from L-tyrosine. The secretory efficiency of mL-AAD conducted by its own twin-arginine signal peptide (twin-arginine translocation pathway, Tat) and integrated pelB (the general secretory pathway, Sec)-Tat signal peptide was determined and compared firstly, using two pET systems (pET28a and pET20b). It was found that the Tat pathway (pET28a-mlaad) resulted in higher cell-associated mL-AAD activity and cell biomass, and was more beneficial to prepare biocatalyst. In addition, expression hosts BI21 (DE3) and 0.05 mmol. L- 1 IPTG were found to be suitable for mL-AAD expression. The reaction conditions for mL-AAD were optimized and 72.72 mmol,L 1 4-HPPA was obtained from 100 mmol.L 1 tyrosine in 10 h under the optimized conditions. This bioprocess, which is more eco-friendly and economical than the traditional chemical synthesis ways, has great potential for industrial application.
基金Supported by the Heart and Stroke Foundation of Canada,No.G-13-0002851the Canadian Institutes of Health Research Training Program in Regenerative Medicine to Bartczak A and Chruscinski Athe Ontario Graduate Scholarship in Science and Technology to Bartczak A
文摘AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODSTreg and Teff cells from fgl2<sup>-/-</sup>, fgl2<sup>+/+</sup>, and fgl2<sup>Tg</sup> mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1<sup>-/-</sup> mice.RESULTSIn vitro, fgl2<sup>Tg</sup> Treg had enhanced immunosuppressive activity, and fgl2<sup>Tg</sup> Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2<sup>+/+</sup>) into Rag1<sup>-/-</sup> mice produced both clinical and histologic colitis with dense infiltrates of CD3<sup>+</sup> T cells, crypt abscesses and loss of goblet cells. Fgl2<sup>Tg</sup> Treg prevented the development of T cell-induced colitis, whereas fgl2<sup>+/+</sup> and fgl2<sup>-/-</sup> Treg were only partially protective. In mice that received fgl2<sup>Tg</sup> Treg, the ratio of Foxp3<sup>+</sup> to CD3<sup>+</sup> cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2<sup>Tg</sup> mice did not produce colitis.CONCLUSIONHere we show that fgl2<sup>Tg</sup> Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2<sup>Tg</sup> Treg prevent colitis in contrast to fgl2<sup>+/+</sup> Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.
基金Supported by the National Natural Science Foundation of China (30630056)the Natural Science Foundation of Chongqing (2006BB5064)
文摘Atrial fibrillation (AF) is the most common arrhythmia with multi-factorial pathogenesis. A number of studies of genetic epidemiology have assessed the association of G112A (G38S) single nucleotide polymorphisms (SNPs) in Mink gene with AF in different populations. However, the results are inconsistent and inconclusive. We performed a Meta-analysis of the association between G112A polymorphisms of MinK gene and AF to estimate the magnitude of the gene effect. Six case-control studies with a combined 854 cases and 1079 controls were summarized. Subgroups in different races were separately analyzed. Heterogeneity and publication bias were also explored. When all groups were pooled, the individuals with G allele had an over 40% higher risk of AF compared with individuals with the A allele. The GG genotype (versus AA genotype) was found to be significant association with increased AF risk. The significant associations were also found in both dominant and recessive genetic model. For subgroup analysis, the results were consistent with above, except that the pooled OR for Chinese population was not significant in a recessive genetic model. In conclusion, G112A polymorphisms in Mink gene may have an important effect on the pathogenesis of AF. This warrants further investigation in large multi-center studies with precise design.
基金Supported by Center of Excellence for Gastrointestinal,Inflammation and Immunity Research at the University of Alberta
文摘AIM: To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in cortico- steroid-free remission. METHODS: Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remis- sion was defined as corticosteroid-free plus normaliza- tion of clinical disease activity [CD activity index (CDAI) 〈 150] during follow-up visits based on physician global assessments. A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI 〉 220) and a thera- peutic intervention with CD medication(s), or a hospital- ization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n -- 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment do- main 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBDS) polymorphisms (IGR2060a1 and IGR3081a1) were ana- lyzed in each group. RESULTS: Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no signifcant increase in frequency of the NOD2/CARD15 polymor- phisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060al and IGR3081a1) in either group of patients; those whose disease relapsed rap- idly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of re- sponse remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked dif- ference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years 4- 0.6 years, while those still in remission were at the time of this study, 8.1 years 4- 2.6 years post-discon- tinuation of infliximab, P 〈 0.001. The 8 patients who had lost remission after discontinuing infiiximab had a mean number of 5 infusions (range 3-7), with a mean treatment time of 7.2 mo (range 1.5 mo-15 mo). The mean duration of time from the last infusion of inflix- imab to the time of loss of remission was 382 d (range 20 d-701 d). The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions (range 3-12), with a mean treatment dura- tion of 12 mo (range 3.6 mo-32 too) (P = 0.45 relative to those who lost remission). CONCLUSION: There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sus- tained remission and which will relapse rapidly after stopping infliximab.
文摘In 2008, two governmental committees presented their conclusions on strengthening the role of the private building sector in building control. In 2011, three new studies were commissioned by the government to address perceived problems. One of them was an integral study, executed by ERB (Foundation Expertcentre Regulations in Building), RIGO (Research Institute for Real Estate) and TNO (Research Institute for Applied Technologies), to innovate the whole building regulations system. It led to proposals to redefine responsibility and liability for all parties. This study states that by an effort of yearly £100 million, unnecessary costs up to £l billion can be avoided and a real quality push will take place in the building and real estate markets. The goals to reach are to minimize the administrative burden for the building owner and to enforce the construction industry to build conforming to the regulations. This paper discusses the ERB study and the given proposals. The ERB study demonstrated that a quality push is needed which potential will lead to less costs for building owners. It also shows that proven solutions, part of the regulations, might be of help for all parties involved.
文摘Advances in clinical and fimdamental research, which have been promoted over last decades have led to a well- established understanding of atrial fibrillation (AF) as an epiphenomenon that despite similar manifestations may have different underlying mechanisms and thus require in- dividualized treatments. With rare exceptions of AF caused by mutations in genes coding ion channels in pa- tients with structurally normal atria, fibrotic replacement of atrial myocardium remains the comer stone of atrial pa- thology in patients with AF.
文摘The empirical study uses black swan approach to analyze the performance of South African (ZA) listed property loan stocks (PLSs). Although there are no empirical studies on black swan perspective and performance of listed real estate funds, the study found that there are similar traits of investing in listed real estate funds from emerging markets' perspective and what black swan advocates such as passive investment strategy and non-normality distribution of returns from listed real estate funds. Furthermore, the individual return of each fund was higher the return of the property loan stocks index and the probabilities of all variables confirm that they (variables) are significant when alpha is 10% at confidence level of 90%.
文摘Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.
基金Supported by National Natural Science Foundation of China,No.81602023
文摘AIM To evaluate PIK3 CA gene mutational status in Northwest Chinese esophageal squamous cell carcinoma(ESCC) patients, and examine the associations of PIK3 CA gene mutations with clinicopathological characteristics and clinical outcome.METHODS A total of 210 patients with ESCC who underwent curative resection were enrolled in this study. Pyrosequencing was applied to investigate mutations in exons 9 and 20 of PIK3 CA gene in 210 Northwest Chinese ESCCs. The associations of PIK3 CA gene mutations with clinicopathological characteristics and clinical outcome were examined.RESULTS PIK3 CA gene mutations in exon 9 were detected in 48 cases(22.9%) of a non-biased database of 210 curatively resected Northwest Chinese ESCCs. PIK3 CA gene mutations were not associated with sex, tobacco use, alcohol use, tumor location, stage, or local recurrence. When compared with wild-type PIK3 CA gene cases, patients with PIK3 CA gene mutations in exons 9 experienced significantly better disease-free survival and overall survival rates.CONCLUSION The results of this study suggest that PIK3 CA gene mutations could act as a prognostic biomarker in Northwest Chinese ESCC patients.