目的探讨伴有MYC基因重排和11q异常的高级别B细胞淋巴瘤(high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberrations,HGBCL-MYC-11q)的临床病理特征、分子遗传学特征、治疗及预后。方法收集3例HGBCL-MYC-11q...目的探讨伴有MYC基因重排和11q异常的高级别B细胞淋巴瘤(high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberrations,HGBCL-MYC-11q)的临床病理特征、分子遗传学特征、治疗及预后。方法收集3例HGBCL-MYC-11q的临床资料,行HE、免疫组化EnVision法染色、EBER原位杂交和FISH检测,并复习相关文献。结果患者均为男性,年龄分别为10、61和74岁。Ann Arbor分期均为Ⅳ期。3例均为活检,分别发生于鼻咽部、上咽部和回盲部。3例形态学相似,肿瘤细胞弥漫浸润性生长,细胞中等大或中等偏大,形态较单一,细胞核圆形到稍不规则,染色质细腻,核分裂象易见;1例局灶可见坏死;1例“星空”现象明显。肿瘤细胞均表达CD20、BCL6和MUM1;2例表达CD10,2例表达BCL2;Ki67增殖指数高(例1、例3近100%,例2约70%);不表达CD3、CD30和TDT;EBER原位杂交检测均为阴性。FISH检测3例均见C-MYC基因重排及11q异常,其中1例仅见11q23.3扩增,1例仅见11q24.3缺失。随访时间1~18个月,1例死亡,2例带病生存。结论HGBCL-MYC-11q少见,形态学类似Burkitt淋巴瘤/高级别B细胞淋巴瘤,但同时伴有MYC基因重排和11q异常,应加强对该疾病的认识,提高对这类疾病的精准诊断及鉴别诊断。展开更多
Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the...Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.展开更多
BACKGROUND Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery.However,some patients may develop postope-rative complications,liver failure,and other life-t...BACKGROUND Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery.However,some patients may develop postope-rative complications,liver failure,and other life-threatening situations.Here,we report a patient with mutations in the uridine 5’-diphospho-glucuronosyltrans-ferase 1A1(UGT1A1)and bile salt export pump(adenosine triphosphate-binding cassette subfamily B member 11,ABCB11)genes who presented multiple intrahe-patic bile duct stones and cholestasis,and the jaundice of the patient increased after partial hepatectomy.CASE SUMMARY A 52-year-old male patient admitted to the hospital on October 23,2021,with a progressive exacerbation of jaundice,was found to have multiple intrahepatic bile duct stones with the diagnoses of obstructive jaundice and acute cholecystitis.Subsequently,the patient underwent left hepatectomy with biliary exploration,stone extraction,T-tube drainage,and cholecystectomy without developing any intraoperative complications.The patient had a dark urine color with worsening jaundice postoperatively and did not respond well to plasma exchange and other symptomatic and supportive treatments.Since the progressive increase in postoperative bilirubin could not be clinically explained with any potential reason,including,if not at all,viral infection,cholangitis,autoimmune liver disease,and other causes,the patient underwent whole-exon screening for any genetic diseases,which surprisingly identified UGT1A1 and ABCB11 gene mutations related to glucuronidation of indirect bilirubin as well as bile acid transport in hepatocytes,respectively.Thus,we hypothesized that postoperative refractory cholestasis might result from UGT1A1 and ABCB11 gene mutations and further recommended liver transplantation to the patient,who eventually declined it and died from liver failure six months later.CONCLUSION Surgery may aggravate cholestasis in patients with multiple intrahepatic bile duct stones and cholestasis associated with UGT1A1 and ABCB11 gene mutations.A liver transplant may be the best option if active medical treatment fails.展开更多
文摘目的探讨伴有MYC基因重排和11q异常的高级别B细胞淋巴瘤(high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberrations,HGBCL-MYC-11q)的临床病理特征、分子遗传学特征、治疗及预后。方法收集3例HGBCL-MYC-11q的临床资料,行HE、免疫组化EnVision法染色、EBER原位杂交和FISH检测,并复习相关文献。结果患者均为男性,年龄分别为10、61和74岁。Ann Arbor分期均为Ⅳ期。3例均为活检,分别发生于鼻咽部、上咽部和回盲部。3例形态学相似,肿瘤细胞弥漫浸润性生长,细胞中等大或中等偏大,形态较单一,细胞核圆形到稍不规则,染色质细腻,核分裂象易见;1例局灶可见坏死;1例“星空”现象明显。肿瘤细胞均表达CD20、BCL6和MUM1;2例表达CD10,2例表达BCL2;Ki67增殖指数高(例1、例3近100%,例2约70%);不表达CD3、CD30和TDT;EBER原位杂交检测均为阴性。FISH检测3例均见C-MYC基因重排及11q异常,其中1例仅见11q23.3扩增,1例仅见11q24.3缺失。随访时间1~18个月,1例死亡,2例带病生存。结论HGBCL-MYC-11q少见,形态学类似Burkitt淋巴瘤/高级别B细胞淋巴瘤,但同时伴有MYC基因重排和11q异常,应加强对该疾病的认识,提高对这类疾病的精准诊断及鉴别诊断。
基金supported by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science(15H04730,16H05186,16K08772,17K12004,19H03467,21J00572)a contract research fund from the Japan Program for Infectious Diseases Research and Infrastructure for research on emerging and re-emerging infectious diseases provided by the Japan Agency for Medical Research and Development(AMED)the Project for Promoting Leading-edge Research in Oral Science at Tokyo Medical and Dental University。
文摘Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.
基金Supported by The Science and Technology Planning Projects of Guizhou Province and Zunyi City,No.QKHJCZK[2022]YB642,No.ZSKH·HZ(2022)344,No.gzwjkj2021-071,ZMC·YZ[2018]38,No.ZSKH·HZ[2021]58,and No.ZSKH·HZ[2021]60The General Project of Hubei Province and Jingmen City,No.2021YFYB074.
文摘BACKGROUND Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery.However,some patients may develop postope-rative complications,liver failure,and other life-threatening situations.Here,we report a patient with mutations in the uridine 5’-diphospho-glucuronosyltrans-ferase 1A1(UGT1A1)and bile salt export pump(adenosine triphosphate-binding cassette subfamily B member 11,ABCB11)genes who presented multiple intrahe-patic bile duct stones and cholestasis,and the jaundice of the patient increased after partial hepatectomy.CASE SUMMARY A 52-year-old male patient admitted to the hospital on October 23,2021,with a progressive exacerbation of jaundice,was found to have multiple intrahepatic bile duct stones with the diagnoses of obstructive jaundice and acute cholecystitis.Subsequently,the patient underwent left hepatectomy with biliary exploration,stone extraction,T-tube drainage,and cholecystectomy without developing any intraoperative complications.The patient had a dark urine color with worsening jaundice postoperatively and did not respond well to plasma exchange and other symptomatic and supportive treatments.Since the progressive increase in postoperative bilirubin could not be clinically explained with any potential reason,including,if not at all,viral infection,cholangitis,autoimmune liver disease,and other causes,the patient underwent whole-exon screening for any genetic diseases,which surprisingly identified UGT1A1 and ABCB11 gene mutations related to glucuronidation of indirect bilirubin as well as bile acid transport in hepatocytes,respectively.Thus,we hypothesized that postoperative refractory cholestasis might result from UGT1A1 and ABCB11 gene mutations and further recommended liver transplantation to the patient,who eventually declined it and died from liver failure six months later.CONCLUSION Surgery may aggravate cholestasis in patients with multiple intrahepatic bile duct stones and cholestasis associated with UGT1A1 and ABCB11 gene mutations.A liver transplant may be the best option if active medical treatment fails.
