Gasdermin D inhibition confers antineutrophil-mediated cardioprotection in acute myocardial infarction

Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis in the infarcted heart remain poorly understood. Using an AMI mouse model, we identified gasdermin D (GSDMD) in activated leukocytes early in AMI. We demonstrated that GSDMD is required for enhanced early mobilization of neutrophils to the infarcted heart. Loss of GSDMD resulted in attenuated IL-1β release from neutrophils and subsequent decreased neutrophils and monocytes in the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function, and increased post-AMI survival. Through a series of bone marrow transplantation studies and leukocyte depletion experiments, we further clarified that excessive bone marrow–derived and GSDMD-dependent early neutrophil production and mobilization (24 hours after AMI) contributed to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection after AMI through a reduction in scar size and enhancement of heart function. Our study provides mechanistic insights into molecular regulation of neutrophil generation and mobilization after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.     

不同氮素形态和浓度水平对浙贝母产量和品质的影响

目的:研究不同氮素形态配施对浙贝母产量和品质的影响,为浙贝母氮肥的科学施用及重庆地区的迁地引种提供依据。方法:采用盆栽试验法,研究了2种氮素形态的5种浓度水平即硝态氮(NO_3~--N)-铵态氮(NH_4~+-N)为15∶0(N1),12∶3(N2),7. 5∶7. 5(N3),3∶12(N4),0∶15(N5)处理下,引种栽培的浙贝母生长及生理生化、土壤因子、生物碱含量及产量的变化。结果:与不施氮(CK)处理组相比,不同氮素营养配施对浙贝母生长和品质均有显著提高,相互间存在差异。其中,随着铵态氮浓度的增加:①在硝态氮-铵态氮比为3∶12时,株高、超氧化物歧化酶(SOD)活性达到最大,较CK组分别增加了9. 27%,206. 62%;②在硝态氮-铵态氮比为0∶15时,叶长,叶宽,茎粗,叶绿素a,叶绿素b,叶绿素总量,速效磷含量,有机质含量、总生物碱含量/产量达到最大,分别高于CK处理组14. 02%,16. 44%,13. 68%,40. 75%,45. 31%,41. 72%,77. 70%,14. 70%,24. 61%/47. 39%;随着硝态氮浓度的增加;③在硝态氮-铵态氮比为7. 5∶7. 5时,叶形指数、可溶性蛋白含量、贝母辛含量/产量、贝母素乙产量、鳞茎干重均达到最大,分别高于CK处理组2. 54%,5. 92%,21. 76%/54. 55%,60. 61%,26. 93%;④在硝态氮-铵态氮比为12∶3时,类胡萝卜素含量、色素含量、过氧化物酶(POD)活性、过氧化氢酶(CAT)活性、贝母素甲含量/产量、贝母素乙含量、贝母素(甲+乙)含量/产量、贝母素(甲+乙)+贝母辛含量/产量、鳞茎湿重均达到最大,分别高于CK处理组45. 39%,45. 31%,271. 38%,67. 45%,39. 82%/64. 87%,36. 01%,38. 90%/63. 80%,37. 03%/61. 57%,20. 29%。结论:较高比例的铵态氮利于浙贝母的生长;而较高比例的硝态氮利于浙贝母鳞茎的生长以及代谢产物生物碱的积累。氮素配比施用(硝态氮-铵态氮比为12:3)较单一形态氮素更有利于提高浙贝母的产量和品质。     

脓毒症相关性脑病的生物学标志物研究进展

脓毒症相关性脑病(SAE)是导致脓毒症患者病死率增高的常见并发症,但其发病机制仍不清楚,无公认的诊断标准,缺乏有效的干预措施。随着对SAE病理生理机制研究的不断深入,探索疾病特异的相关生物标志物对寻找有效的诊疗手段有一定意义。     

Subcutaneous granuloma caused by Kodamaea ohmeri in an immunocompromised patient in China

We present a case of subcutaneous granuloma caused by Kodamaea ohmeri and describe the histopathological characteristics and skin lesions caused by this pathogen. A 55-year-old woman, with a history of rheumatoid arthritis, presented with red, painless plaque on her forehead, persistent for 3 months; based on the histopathological and mycological findings and gene sequencing, the patient was diagnosed with subcutaneous granuloma caused by K. ohmeri. This report highlights that early identification and diagnosis and optimal regimens are vital in the management of this intractable infection.     

男性杓状软骨钙化对喉接触性肉芽肿治疗效果的影响

研究杓状软骨钙化对喉接触性肉芽肿治疗效果的影响。方法对临床资料完整的 115 例喉接触性肉芽肿男性患者进行回顾性分析,统计患侧杓状软骨钙化对治疗效果的影响。结果115 例男性喉接触性肉芽肿患者,年龄22~68岁,平均年龄45.82 岁。其中单侧肉芽肿 110（110/115,95.65 %）,双侧肉芽肿 5 例（5/115.35%）;病因中有反流病史 67 例（67/115,58.26%）,插管诱发 5 例（5/115,4.35%）,其余患者无明显原因。115例男性患者 CT 显示杓状软骨伴钙化 102例（102/115,88.70%）,杓状软骨无钙化13 例（13/115;11.30%）。其中杓状软骨伴钙化患者治愈时间＞3个月 68 例,治愈时间≤3 个月 34 例;杓状软骨无钙化治愈时间＞3个月患者 4 例,治愈时间≤3个月 9 例。通过 Chi square 检验分析显示患者杓状软骨伴钙化的治愈时间＞3个月的百分数明显多于不伴钙化组（χ2=4.906,P=0.027）。结论喉接触性肉芽肿患者,杓状软骨钙化的患者治疗时间较长,可能是由于这类患者长期慢性炎性刺激引起杓状软骨钙化,病程相对较长,治疗困难。