BACKGROUND Malignant obstructive jaundice(MOJ)is a common pathologic manifestation of malignant biliary obstruction.Recently,several clinical trials have explored the clinical effectiveness of intraluminal^(125)I seed...BACKGROUND Malignant obstructive jaundice(MOJ)is a common pathologic manifestation of malignant biliary obstruction.Recently,several clinical trials have explored the clinical effectiveness of intraluminal^(125)I seed-based brachytherapy for MOJ patients,and various outcomes have been reported.AIM To assess the efficacy and safety of percutaneous biliary stents with^(125)I seeds compared to conventional metal stents in patients with unresectable MOJ.METHODS A systematic search of English-language databases(PubMed,Embase,Cochrane Library,and Web of Science)was performed to identify studies published prior to June 2020 that compared stents with or without^(125)I seeds in the treatment of unresectable MOJ.The outcomes analyzed included primary outcomes(stent patency and overall survival)and secondary outcomes(complications and liver function parameters).RESULTS Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis.Of the 875 included patients,404 were treated with^(125)I seed stents,while 471 were treated with conventional stents.Unadjusted pooled analysis demonstrated that compared to conventional stents,^(125)I seed stents extended the stent patency time[hazard ratio(HR)=0.36,95%confidence interval(CI)=0.28-0.45,P<0.0001]and overall survival period(HR=0.52,95%CI=0.42–0.64,P<0.00001).Subgroup analyses based on the type of^(125)I seed stent and type of study design showed consistent results.However,there were no significant differences in the occurrence of total complications[odds ratio(OR)=1.12,95%CI=0.75-1.67,P=0.57],hemobilia(OR=1.02,95%CI=0.45-2.3,P=0.96),pancreatitis(OR=1.79,95%CI=0.42-7.53,P=0.43),cholangitis(OR=1.13,95%CI=0.60-2.13,P=0.71),or pain(OR=0.67,95%CI=0.22-2,P=0.47).In addition,there were no reductions in the levels of serum indices,including total bilirubin[mean difference(MD)=10.96,95%CI=-3.56-25.49,P=0.14],direct bilirubin(MD=7.37,95%CI=-9.76-24.5,P=0.4),alanine aminotransferase(MD=7.52,95%CI=-0.71-15.74,P=0.07),and aspartate aminotransferase(MD=-4.77,95%CI=-19.98-10.44,P=0.54),after treatment.Publication bias was detected regarding the outcome overall survival;however,the conclusions were not changed after the adjustment.CONCLUSION Placement of stents combined with brachytherapy using^(125)I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage.Thus,it can be considered an effective and safe treatment for unresectable MOJ.展开更多
BACKGROUND Ankylosing spondylitis(AS)is an autoimmune disease characterized by sacroiliitis and spondylitis,with a few hematological abnormalities.Myelodysplastic syndromes(MDS)are a heterogeneous group of hematopoiet...BACKGROUND Ankylosing spondylitis(AS)is an autoimmune disease characterized by sacroiliitis and spondylitis,with a few hematological abnormalities.Myelodysplastic syndromes(MDS)are a heterogeneous group of hematopoietic stem cell disorders with frequent autoimmune phenomena.The relationship between AS and MDS remains unknown.CASE SUMMARY We describe a rare case of concurrent AS and MDS.An 18-year-old man with low back pain and anemia was diagnosed with AS;however,the cause of anemia could not be determined by the first bone marrow examination.He recovered from anemia and the symptoms of AS resolved after treatment with etanercept,glucocorticoid,and blood transfusion,but he developed pancytopenia with an increased myeloblast count(from 2.5%to 9%).Chromosome analysis revealed del(7q)and trisomy 8.Refractory anemia with excess of blasts-1(RAEB-1)/MDS was confirmed by repeating the bone marrow examination.He became blood transfusion-dependent and received decitabine-based chemotherapy but eventually died.CONCLUSION We suspect that AS may be an early autoimmune phenomenon related to MDS.However,a condition of coexistence cannot be excluded.展开更多
Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell prolifer...Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P〈0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P 〈 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P 〈 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P 〈0.05).The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.展开更多
基金the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2020KY1086 and No.2020KY1087.
文摘BACKGROUND Malignant obstructive jaundice(MOJ)is a common pathologic manifestation of malignant biliary obstruction.Recently,several clinical trials have explored the clinical effectiveness of intraluminal^(125)I seed-based brachytherapy for MOJ patients,and various outcomes have been reported.AIM To assess the efficacy and safety of percutaneous biliary stents with^(125)I seeds compared to conventional metal stents in patients with unresectable MOJ.METHODS A systematic search of English-language databases(PubMed,Embase,Cochrane Library,and Web of Science)was performed to identify studies published prior to June 2020 that compared stents with or without^(125)I seeds in the treatment of unresectable MOJ.The outcomes analyzed included primary outcomes(stent patency and overall survival)and secondary outcomes(complications and liver function parameters).RESULTS Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis.Of the 875 included patients,404 were treated with^(125)I seed stents,while 471 were treated with conventional stents.Unadjusted pooled analysis demonstrated that compared to conventional stents,^(125)I seed stents extended the stent patency time[hazard ratio(HR)=0.36,95%confidence interval(CI)=0.28-0.45,P<0.0001]and overall survival period(HR=0.52,95%CI=0.42–0.64,P<0.00001).Subgroup analyses based on the type of^(125)I seed stent and type of study design showed consistent results.However,there were no significant differences in the occurrence of total complications[odds ratio(OR)=1.12,95%CI=0.75-1.67,P=0.57],hemobilia(OR=1.02,95%CI=0.45-2.3,P=0.96),pancreatitis(OR=1.79,95%CI=0.42-7.53,P=0.43),cholangitis(OR=1.13,95%CI=0.60-2.13,P=0.71),or pain(OR=0.67,95%CI=0.22-2,P=0.47).In addition,there were no reductions in the levels of serum indices,including total bilirubin[mean difference(MD)=10.96,95%CI=-3.56-25.49,P=0.14],direct bilirubin(MD=7.37,95%CI=-9.76-24.5,P=0.4),alanine aminotransferase(MD=7.52,95%CI=-0.71-15.74,P=0.07),and aspartate aminotransferase(MD=-4.77,95%CI=-19.98-10.44,P=0.54),after treatment.Publication bias was detected regarding the outcome overall survival;however,the conclusions were not changed after the adjustment.CONCLUSION Placement of stents combined with brachytherapy using^(125)I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage.Thus,it can be considered an effective and safe treatment for unresectable MOJ.
基金Supported by National Natural Science Foundation of China,No.81701600.
文摘BACKGROUND Ankylosing spondylitis(AS)is an autoimmune disease characterized by sacroiliitis and spondylitis,with a few hematological abnormalities.Myelodysplastic syndromes(MDS)are a heterogeneous group of hematopoietic stem cell disorders with frequent autoimmune phenomena.The relationship between AS and MDS remains unknown.CASE SUMMARY We describe a rare case of concurrent AS and MDS.An 18-year-old man with low back pain and anemia was diagnosed with AS;however,the cause of anemia could not be determined by the first bone marrow examination.He recovered from anemia and the symptoms of AS resolved after treatment with etanercept,glucocorticoid,and blood transfusion,but he developed pancytopenia with an increased myeloblast count(from 2.5%to 9%).Chromosome analysis revealed del(7q)and trisomy 8.Refractory anemia with excess of blasts-1(RAEB-1)/MDS was confirmed by repeating the bone marrow examination.He became blood transfusion-dependent and received decitabine-based chemotherapy but eventually died.CONCLUSION We suspect that AS may be an early autoimmune phenomenon related to MDS.However,a condition of coexistence cannot be excluded.
基金This work was supported in part by grants from the National Natural Science Foundation of China (81072480), from the Natural Science Foundation of Guangdong Province ($2012020010927), and from the Science and Technology Program of Guangdong Province (2013B021800076) (Jian-lin Huang) the major projects from Science and Technology Program of Guangzhou City, from the National Natural Science Foundation of Guangdong Province, from the Department of Education of Guangdong Province, and grants from NIH AR059103 and NIH AI084359 (Song Guo Zheng).
文摘Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P〈0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P 〈 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P 〈 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P 〈0.05).The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.