活体大蒜及离体蒜苗对连作当归胁迫的影响

目的:通过活体大蒜(garlic)及离体蒜苗(garlic sprout)挥发物对当归(Angelica sinensis)的化感效应,探索大蒜挥发性物质对连作当归存在的化感效应,为当归大蒜间作模式缓解连作当归胁迫提供一定的理论依据。方法:试验通过对当归各生长指标及叶片保护酶系统的测定分析,讨论当归在活体大蒜及离体蒜苗挥发物的影响作用下对连作胁迫、无连作胁迫环境的适应性及抗性生长发育机制。结果:整体分析,连作胁迫条件下离体蒜苗对当归幼苗化感效应处理(DC2)下的当归生长指标、叶片保护酶活性较当归单作(CK1)整体提高17. 51%,48. 34%;连作茬口种植活体蒜苗与当归间作处理(LC2)下的当归生长指标、叶片保护酶活性较当归单作(CK2)整体提高16. 63%,36. 65%;即离体蒜苗挥发物较活体大蒜缓解当归连作胁迫作用更显著。结论:无论有无连作障碍胁迫,适当浓度的活体大蒜及离体蒜苗挥发物对当归生长指标及叶片保护酶活性均表现为明显的化感促进作用,其化感促进作用在有连作胁迫条件下表现更显著,因而间作大蒜对当归连作障碍胁迫有一定的缓解作用。     

Primary Conservative Therapy for Symptomatic Isolated Mesenteric Artery Dissection with Severely Compressed True Lumen or Large Dissecting Aneurysm

PurposeTo investigate the safety and effectiveness of primary conservative therapy for patients with symptomatic isolated mesenteric artery dissection (IMAD) with a severely compressed true lumen and/or a large dissecting aneurysm.Materials and MethodsA total of 35 consecutive patients (all men; median age, 53 y) with symptomatic IMAD with a severely compressed true lumen and/or a large dissecting aneurysm but without intestinal necrosis or arterial rupture who were treated with primary conservative therapy between November 2018 and February 2020 were assessed. A severely compressed true lumen was defined as luminal stenosis > 70%. A large dissecting aneurysm was defined as dissecting aneurysm diameter ≥ 1.5 times larger than the normal mesenteric artery diameter.ResultsThere was a strong positive relationship among abdominal pain, degree of luminal stenosis, and length of dissection (R = 0.811; P < .001). Conservative treatment was successful in all patients. Abdominal pain was eliminated within 4.7 d ± 4.8 (range, 2–31 d) in all patients, within 3.6 d ± 1.2 (range, 2–6) in the 31 patients with minor or moderate abdominal pain, and within 13.3 d ± 11.9 (range, 6–31 d) in the 4 patients with severe abdominal pain. Complete or partial remodeling of the mesenteric artery was achieved in 6 (17.1%) and 29 (82.9%) patients, respectively, during 8.6 mo ± 4.3 of follow-up.ConclusionsPrimary conservative therapy can be used safely and effectively in patients with symptomatic IMAD with a severely compressed true lumen and/or a large dissecting aneurysm but without intestinal necrosis or arterial rupture.     

Preclinical approaches to assess potential kinase inhibitor‐induced cardiac toxicity: Past,present and future

Over a decade ago, use of tyrosine kinase inhibitors (TKIs) for the treatment of malignancies was found to cause left ventricular dysfunction, a finding that was unexpected and not well predicted by standard preclinical studies. Subsequently, several preclinical approaches were proposed to address this issue. Over the last 5 years, several approaches for preclinical evaluation of cardiac function using isolated perfused hearts, engineered heart tissue and human‐induced pluripotent stem cell‐derived cardiac myocytes have been shown to be relatively predictive of the cardiotoxic potential of TKIs. Further, preclinical studies submitted for regulatory review for recently approved KIs have demonstrated various forms of KI‐induced cardiotoxicity. Thus, early identification and assessment of cardiotoxicity in the preclinical setting is now possible. Given that kinases are involved in diverse cellular processes common to both normal and tumor cells, KI‐induced toxicity, particularly in the heart, appears difficult to avoid. To develop drugs with fewer adverse effects, better efficacy and safety assessments, such as pharmacological separation of targets for cancer from heart, and/or wider separation of the drug concentrations for antitumor activity from cardiac toxicity, may be helpful. Additional preclinical approaches for assessing drug efficacy and toxicity in parallel may include use of animal cancer models and a 3D integrated in vitro model of perfused tumor and heart tissues. Minimizing and predicting potential KI‐induced cardiotoxicity is still an important regulatory challenge, and better preclinical approaches may help achieve this goal.     

注射用糜蛋白酶中组胺类物质检查方法学研究

【摘要】目的：建立注射用糜蛋白酶中组胺类物质检查方法。 方法：采用组胺检查法对注射用糜蛋白酶中组胺类物质进行限度检查方法学研究,并与现行猫法进行比较研究。结果：加标回收率86%～117%;豚鼠法方法特异性(真阴性率)100%,灵敏度(真阳性率)70%,猫法方法特异性100%,灵敏度70%;四个实验室室内重复性分别为82%、75%、83%、81%;实验室间重复性为92.9%～96.4%.结论：该方法准确与猫法相当、重复性好,可作为降压物质检查法的替代方法。     

Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes

The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled “any other single” and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the “real” prognostic impact of der(1;7) on a homogenous and well‐documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.     

Novel missense mutation in VPS33B is associated with isolated low gamma‐glutamyltransferase cholestasis: Attenuated,incomplete phenotype of arthrogryposis,renal dysfunction,and cholestasis syndrome

The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma‐glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low‐GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in‐vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.     

注射用益气复脉(冻干)安全性评价

目的 通过豚鼠离体回肠模型及小鼠类致敏实验评价注射用益气复脉（冻干,YQFM）的安全性。方法 建立豚鼠离体回肠模型,依次考察0.2、0.4、0.6、0.8、1.2、1.4、1.6 mg/mL质量浓度的YQFM对静息离体肠、乙酰胆碱（Ach）及组胺（His）诱导的离体肠收缩的抑制率;雄性ICR小鼠随机分为阴性对照组,阳性对照组（C48/80,25 mg/kg）,YQFM低、高剂量（780、3 135 mg/kg,分别为临床等效剂量的0.85和3.43倍）组,分为尾iv含0.4%伊文思蓝（EB）的药液及不含0.4% EB的药液两部分进行体内类致敏反应实验,依次比较各组小鼠耳廓蓝染情况;ELISA法测定血清中His和5-羟色胺（5-HT）的含量;并对耳、肺组织进行HE染色及病理检查。结果 体外实验显示,YQFM既能够抑制离体肠的自主收缩,又能抑制Ach和His导致的离体肠痉挛;体内实验表明,YQFM低剂量组耳廓蓝染率,His、5-HT含量均在正常范围,组织病理检查未见明显异常;3.43倍临床等效剂量时耳廓蓝染率,His、5-HT含量略高,病理结果见轻微炎症反应。结论 YQFM的安全性基本良好,临床使用时需对使用剂量稍加注意,以防轻微不良反应发生。