This trial examined the safety and possible MRI and clinical effects of anti - chlamydial antibiotic therapy in relapsing- remitting MS (RRMS). Newly diagn osed MS patients were selected to participate if they showed ...This trial examined the safety and possible MRI and clinical effects of anti - chlamydial antibiotic therapy in relapsing- remitting MS (RRMS). Newly diagn osed MS patients were selected to participate if they showed Chlamydia pneumonia e gene in their CSF and had one or more enhancing lesions on brain magnetic reso nance imaging (MRI). After a 4- month run in phase of monthly MRI, patients wer e randomized to receive rifampin (300 mg twice daily) and azithromycin (500 mg e very other day) for 6 months or placebo (PBO). Patients then had monthly MRI on therapy and two additional scans on months 12 and 14. Lumbar punctures were repe ated between months 7 and 8 and within 2 weeks of termination of the study. Data on 4 patients on treatment and 4 on PBO were available for analysis. The primar y outcome measure of showing a beneficial effect on enhancing lesions was not me t. However, there was a significant difference in brain parenchymal fraction los s favoring those patient receiving antibiotics compared with PBO (p ≤ 0.02). Th ree of the four patients on antibiotic therapy cleared the organism from the CSF by month 12; in the PBO group one patient cleared the organism. The reduction i n atrophy in patients receiving antibiotics must be viewed with caution, due to the small number of patients studied.展开更多
Multiple sclerosis (MS) is an inflammatory demyelinating disease of central nervous system (CNS) that mostly affects young adults. The etiology of MS includes both genetic and environmental factors. A single nucleotid...Multiple sclerosis (MS) is an inflammatory demyelinating disease of central nervous system (CNS) that mostly affects young adults. The etiology of MS includes both genetic and environmental factors. A single nucleotide polymorphism (SNP) linked with autoimmune disorders predisposition, identified by Genome-Wide Association Study (GWAS) among genes which immunologically related are considerably over signified. The goal of the current study is investigation of the association between rs1800795 (-174 G/C) polymorphism in the promoter of IL6 gene variant with the risk of RRMS in a subset of Iranian population. In this case-control study, 110 healthy subjects and 110 patients with RRMS were included. DNA was extracted from blood samples and polymerase chain reaction (PCR) was used to amplify the fragment of interest contain rs1800795 SNP, restriction fragment length polymorphism (RFLP) method was performed for genotyping of the DNA samples with a specific restriction enzyme (NlaIII). SPSS for Windows software (version 18.0;SPSS, Chicago, IL) was used for statistical analysis. No significant differences were found between RRMS patients and healthy controls with respect to the distribution of the cytokine gene polymorphism investigated. Odds ratio adjusted for age, sex, and blood groups (except A blood group) has displayed similar outcomes. These results indicate that the rs1800795 SNP is not a susceptibility gene variant for development of RRMS in the Isfahan population. Further studies using new data on complex transcriptional interactions between IL-6 polymorphic sites are necessary to determine IL-6 haplotype influence on susceptibility to RRMS.展开更多
Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of t...Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray mat ter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. Obj ectives: To characterize the evolution of GM and WM volumes over 2 years, and th eir associations with lesion loads in a cohort of patients with clinically early RRMS. Methods: Twenty-one patients with RRMS (mean age 37.5 years, mean diseas e duration from symptom onset 2.1 years) and 10 healthy control subjects (mean a ge 37.1 years)-were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1-and 2-year follow-up. Brain parenc hymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated . In subjects with MS, brain lesion loads were determined on conventional T2-we ighted along with pre-and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. Results: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1%vs -1.0%, p=0.044), while no change was seen in WMF over the same period (mean -0.09%vs +0.09%, p=0.812). However, when the MS cohort was divided in half, dependent upon chang e in Gd-enhancing lesion load over 2 years (n=20), a decrease in WMF was seen i n the group (n=10) with the largest decline in Gd volume, whereas WMF increased in the other half (n=10) concurrent with a net increase in volume of Gd-enhanci ng lesions (difference between groups: p=0.034). Conclusions: Increasing gray ma tter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM les ions appear to be related to volume changes in WM over this time period.展开更多
Objective: To assess the efficacy of interferon beta-1b (IFNβ-1b) in Japane se patients with relapsing-remitting multiple sclerosis (RRMS). Background: The effects of IFNβin RRMS have been assessed in study populati...Objective: To assess the efficacy of interferon beta-1b (IFNβ-1b) in Japane se patients with relapsing-remitting multiple sclerosis (RRMS). Background: The effects of IFNβin RRMS have been assessed in study populations comprised predo minantly of white patients. MS in Japanese patients is different from that in wh ite patients in that there are two different presentations classic MS (C-MS) an d optic-spinal MS (OS-MS)and chronic progressive forms are infrequent. Methods : A total of 205 Japanese patients with RRMS were randomized to receive 50 μg o r 250 μg (1.6 or 8.0 MIU) IFNβ-1b administered SC every other day for up to 2 years. The primary endpoint was annual relapse rate. Secondary endpoints includ ed further relapse-related and MRI outcome measures, as well as changes in Expa nded Disability Status Scale and Neurologic Rating Scale.Efficacy was assessed i n 188 patients, and safety was assessed in 192 patients. Supplemental ad hoc sub group analyses were also performed for patients with OS-MS and those with C-MS .Results: Annual relapse rates were 0.763 in the 250 μg group and 1.069 in the 50 μg group, a relative reduction of 28.6%(p = 0.047). Results for all seconda ry endpoints favored 250μg IFNβ-1b. Subgroup analyses suggested that the magn itude and direction of treatment effect in patients with OS-MS and C-MS was si milar, albeit not significant due to small sample size. Conclusions: Interferon beta-1b (IFNβ-1b) 250 μg significantly reduced relapse rates and change in M RI lesion area in Japanese patients with relapsing-remitting multiple sclerosis ,and seemed to be comparably effective in optic-spinal multiple sclerosis (MS) and classic MS. The response to treatment with IFNβ1b in Japanese patients with MS suggests that a common pathogenesis and underlying genetic characteristics a re shared with white patients.展开更多
BACKGROUND Pancreatic cancer(PC)remains one of the most aggressive malignancies,is charac-terized by rapid progression and high metastatic potential,and is the fourth leading cause of cancer-related mortality worldwid...BACKGROUND Pancreatic cancer(PC)remains one of the most aggressive malignancies,is charac-terized by rapid progression and high metastatic potential,and is the fourth leading cause of cancer-related mortality worldwide.The incidence and mortality rates of PC continue to rise annually.Despite advances in imaging technologies and treatment strategies over the past two decades,the 5-year survival rate for patients with PC remains low,at approximately 13%.Patients with advanced PC still experience dismal outcomes,primarily due to the tumor's aggressiveness and high metastatic capacity.Thus,there is an urgent need to identify reliable mole-cular biomarkers and therapeutic targets to improve the prognosis of patients with PC.We comprehensively investigated the expression pattern and functional signi-ficance of DDX10 in PC using a multi-omics integrative approach.We performed bioinformatics analyses of datasets from The Cancer Genome Atlas and Gene Expression Omnibus,tissue microarray-based immunohistochemistry,and a series of in vitro functional assays to assess cellular proliferation,migration,inva-sion,and apoptosis.Additionally,transcriptomic and proteomic analyses were integrated to delineate the molecular regulatory networks that mediate the aggressive phenotype of PC.RESULTS DDX10 was found to be significantly overexpressed at both the mRNA and protein levels in PC tissues compared with adjacent non-tumor tissues.Silencing DDX10 in vitro led to marked inhibition of PC cell proliferation,migration,and invasion,accompanied by enhanced apoptosis.Integrated RNA sequencing,proteomic profiling,and western blot validation revealed that DDX10 modulates key oncogenes including RRM2,LIG1,CDK6,and ITGA2.Notably,ectopic RRM2 overexpression partially rescued the growth-suppressive effects induced by DDX10 knockdown in PANC-1 cells,and high DDX10 expression is associated with poor overall survival in patients with PC.CONCLUSION Collectively,our findings indicate that DDX10 promotes PC cell proliferation primarily by upregulating RRM2,thus highlighting its potential as a promising therapeutic target in PC.展开更多
文摘This trial examined the safety and possible MRI and clinical effects of anti - chlamydial antibiotic therapy in relapsing- remitting MS (RRMS). Newly diagn osed MS patients were selected to participate if they showed Chlamydia pneumonia e gene in their CSF and had one or more enhancing lesions on brain magnetic reso nance imaging (MRI). After a 4- month run in phase of monthly MRI, patients wer e randomized to receive rifampin (300 mg twice daily) and azithromycin (500 mg e very other day) for 6 months or placebo (PBO). Patients then had monthly MRI on therapy and two additional scans on months 12 and 14. Lumbar punctures were repe ated between months 7 and 8 and within 2 weeks of termination of the study. Data on 4 patients on treatment and 4 on PBO were available for analysis. The primar y outcome measure of showing a beneficial effect on enhancing lesions was not me t. However, there was a significant difference in brain parenchymal fraction los s favoring those patient receiving antibiotics compared with PBO (p ≤ 0.02). Th ree of the four patients on antibiotic therapy cleared the organism from the CSF by month 12; in the PBO group one patient cleared the organism. The reduction i n atrophy in patients receiving antibiotics must be viewed with caution, due to the small number of patients studied.
文摘Multiple sclerosis (MS) is an inflammatory demyelinating disease of central nervous system (CNS) that mostly affects young adults. The etiology of MS includes both genetic and environmental factors. A single nucleotide polymorphism (SNP) linked with autoimmune disorders predisposition, identified by Genome-Wide Association Study (GWAS) among genes which immunologically related are considerably over signified. The goal of the current study is investigation of the association between rs1800795 (-174 G/C) polymorphism in the promoter of IL6 gene variant with the risk of RRMS in a subset of Iranian population. In this case-control study, 110 healthy subjects and 110 patients with RRMS were included. DNA was extracted from blood samples and polymerase chain reaction (PCR) was used to amplify the fragment of interest contain rs1800795 SNP, restriction fragment length polymorphism (RFLP) method was performed for genotyping of the DNA samples with a specific restriction enzyme (NlaIII). SPSS for Windows software (version 18.0;SPSS, Chicago, IL) was used for statistical analysis. No significant differences were found between RRMS patients and healthy controls with respect to the distribution of the cytokine gene polymorphism investigated. Odds ratio adjusted for age, sex, and blood groups (except A blood group) has displayed similar outcomes. These results indicate that the rs1800795 SNP is not a susceptibility gene variant for development of RRMS in the Isfahan population. Further studies using new data on complex transcriptional interactions between IL-6 polymorphic sites are necessary to determine IL-6 haplotype influence on susceptibility to RRMS.
文摘Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray mat ter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. Obj ectives: To characterize the evolution of GM and WM volumes over 2 years, and th eir associations with lesion loads in a cohort of patients with clinically early RRMS. Methods: Twenty-one patients with RRMS (mean age 37.5 years, mean diseas e duration from symptom onset 2.1 years) and 10 healthy control subjects (mean a ge 37.1 years)-were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1-and 2-year follow-up. Brain parenc hymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated . In subjects with MS, brain lesion loads were determined on conventional T2-we ighted along with pre-and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. Results: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1%vs -1.0%, p=0.044), while no change was seen in WMF over the same period (mean -0.09%vs +0.09%, p=0.812). However, when the MS cohort was divided in half, dependent upon chang e in Gd-enhancing lesion load over 2 years (n=20), a decrease in WMF was seen i n the group (n=10) with the largest decline in Gd volume, whereas WMF increased in the other half (n=10) concurrent with a net increase in volume of Gd-enhanci ng lesions (difference between groups: p=0.034). Conclusions: Increasing gray ma tter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM les ions appear to be related to volume changes in WM over this time period.
文摘Objective: To assess the efficacy of interferon beta-1b (IFNβ-1b) in Japane se patients with relapsing-remitting multiple sclerosis (RRMS). Background: The effects of IFNβin RRMS have been assessed in study populations comprised predo minantly of white patients. MS in Japanese patients is different from that in wh ite patients in that there are two different presentations classic MS (C-MS) an d optic-spinal MS (OS-MS)and chronic progressive forms are infrequent. Methods : A total of 205 Japanese patients with RRMS were randomized to receive 50 μg o r 250 μg (1.6 or 8.0 MIU) IFNβ-1b administered SC every other day for up to 2 years. The primary endpoint was annual relapse rate. Secondary endpoints includ ed further relapse-related and MRI outcome measures, as well as changes in Expa nded Disability Status Scale and Neurologic Rating Scale.Efficacy was assessed i n 188 patients, and safety was assessed in 192 patients. Supplemental ad hoc sub group analyses were also performed for patients with OS-MS and those with C-MS .Results: Annual relapse rates were 0.763 in the 250 μg group and 1.069 in the 50 μg group, a relative reduction of 28.6%(p = 0.047). Results for all seconda ry endpoints favored 250μg IFNβ-1b. Subgroup analyses suggested that the magn itude and direction of treatment effect in patients with OS-MS and C-MS was si milar, albeit not significant due to small sample size. Conclusions: Interferon beta-1b (IFNβ-1b) 250 μg significantly reduced relapse rates and change in M RI lesion area in Japanese patients with relapsing-remitting multiple sclerosis ,and seemed to be comparably effective in optic-spinal multiple sclerosis (MS) and classic MS. The response to treatment with IFNβ1b in Japanese patients with MS suggests that a common pathogenesis and underlying genetic characteristics a re shared with white patients.
基金Supported by National Natural Science Foundation of China,No.82160588Health Commission of Gansu Province,No.GSWSKY2021-032+1 种基金Natural Science Foundation of Gansu Province,No.24JRRA585Gansu Provincial Hospital Science and Technology Innovation Platform Fund Project,No.21GSSYB-23.
文摘BACKGROUND Pancreatic cancer(PC)remains one of the most aggressive malignancies,is charac-terized by rapid progression and high metastatic potential,and is the fourth leading cause of cancer-related mortality worldwide.The incidence and mortality rates of PC continue to rise annually.Despite advances in imaging technologies and treatment strategies over the past two decades,the 5-year survival rate for patients with PC remains low,at approximately 13%.Patients with advanced PC still experience dismal outcomes,primarily due to the tumor's aggressiveness and high metastatic capacity.Thus,there is an urgent need to identify reliable mole-cular biomarkers and therapeutic targets to improve the prognosis of patients with PC.We comprehensively investigated the expression pattern and functional signi-ficance of DDX10 in PC using a multi-omics integrative approach.We performed bioinformatics analyses of datasets from The Cancer Genome Atlas and Gene Expression Omnibus,tissue microarray-based immunohistochemistry,and a series of in vitro functional assays to assess cellular proliferation,migration,inva-sion,and apoptosis.Additionally,transcriptomic and proteomic analyses were integrated to delineate the molecular regulatory networks that mediate the aggressive phenotype of PC.RESULTS DDX10 was found to be significantly overexpressed at both the mRNA and protein levels in PC tissues compared with adjacent non-tumor tissues.Silencing DDX10 in vitro led to marked inhibition of PC cell proliferation,migration,and invasion,accompanied by enhanced apoptosis.Integrated RNA sequencing,proteomic profiling,and western blot validation revealed that DDX10 modulates key oncogenes including RRM2,LIG1,CDK6,and ITGA2.Notably,ectopic RRM2 overexpression partially rescued the growth-suppressive effects induced by DDX10 knockdown in PANC-1 cells,and high DDX10 expression is associated with poor overall survival in patients with PC.CONCLUSION Collectively,our findings indicate that DDX10 promotes PC cell proliferation primarily by upregulating RRM2,thus highlighting its potential as a promising therapeutic target in PC.
