The immunosuppressive characteristics of FB1 by inhibition of maturation and function of BMDCs

Fumonisin B₁ (FB₁) is one kind of mycotoxins that has the neurotoxicity, carcinogenicity, hepatotoxicity and immunotoxicity produced by the fungus Fusarium verticillioides, which commonly infects corn and other crops and is harmful to animal and human health upon consumption of FB₁-contaminated feed or food. However, the mechanism of immunotoxicity, especially the immunosuppression induced by FB₁ is still unclear. The most pivotal cells in the induction of immune responses are dendritic cells (DCs). In this study, we used murine bone marrow-derived dendritic cells (BMDCs) as a model system to elucidate the effect of FB₁ on the function of BMDCs through biological methods. We found that FB₁ reversed the morphological changes and enhanced the endocytosis of FITC-dextran in LPS-treated BMDCs. At the same time, FB₁ decreased the LPS-induced expressions of MHC II, C[1]D80 and CD86 molecules in BMDCs (p < 0.05), as well as the T-cell stimulatory capacity of BMDCs (p < 0.01). Moreover, the secretions of IL-6, IL-10 and IL-12, but not TNF-α induced by LPS exposure were suppressed by FB₁ in a dose dependent (p < 0.01). It was considered that the immunosuppressive effects of FB₁ were mainly caused by changing the morphology and interfering with the process of antigen uptake, processing and presentation. The results highlighted that FB₁ had the capacity to modulate the immune responses of BMDCs.     

Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in dystonia cases vs. controls

BackgroundHarmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson's disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness.ObjectivesWe assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls.MethodsBlood [HA] was quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls.ResultsMean log blood [HA] in dystonia cases was similar to that of controls (0.41 ± 0.51 g⁻¹⁰/ml vs. 0.38 ± 0.61 g⁻¹⁰/ml, t = 0.42, p = 0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR)_unadjusted = 1.11, 95% confidence interval (CI) = 0.69–1.79, p = 0.68; OR_adjusted = 1.07, 95% CI = 0.58–1.97, p = 0.84.ConclusionsIn contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson's disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders.     

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.     

河南“4.26”60Co源辐射事故一例受照者患非霍奇金淋巴瘤的病因探讨

关于电离辐射是否可诱发非霍奇金淋巴瘤（NHL）,目前的研究结果尚未获得一致结论。笔者报道了河南“4.26” 60Co源辐射事故中1例中度骨髓型急性放射病患者受照后第13年患NHL的病例,结合患者的受照史、病史特点、诊断及国际多项大型研究,从流行病学资料和影响因素两方面分析了患者“天”患非霍奇金淋巴瘤与电离辐射的关系,为电离辐射致NHL提供辐射流行病学依据。     

神经上皮细胞转化基因1对细胞辐射敏感性的影响及其机制探讨

目的 探讨神经上皮细胞转化基因1(Net1)对细胞辐射敏感性的影响及相关的分子作用机制.方法 运用实时荧光定量PCR检测辐射后细胞中Net1基因表达水平的变化;采用RNAi干扰技术抑制细胞中Net1的表达,用克隆形成率分析细胞的辐射敏感性;利用免疫共沉淀技术发现Net1的结合蛋白.结果 电离辐射损伤后,细胞中的Net1 mRNA水平显著上升(t=-10.52,P＜0.05);与对照组相比,siRNA沉默细胞中的Net1表达后明显增加了细胞的辐射敏感性(t=15.31、11.65,P＜0.05);无论在正常状态下还是在细胞受到辐照后,Net1都能与非同源末端连接修复蛋白Ku70、Ku80和DNA-PKcs结合.结论 Net1对细胞的辐射防护作用可能是通过与非同源末端连接修复蛋白相互作用来调控辐射损伤修复实现的.     

Distinguishing Characteristics of Urothelial Carcinoma in Kidney Transplant Recipients Between China and Western Countries

Objective

To identify significant distinctive characteristics of urothelial carcinoma (UC) in kidney transplant recipients between China and Western countries and investigate probable tumor screening and treatment factors contributing to these differences.

Methods

Renal transplant recipients from 1998 to 2011 in our institution diagnosed with UC were included in this study. Our data on tumor incidence, clinical characteristics, and outcomes were compared with literature reports.

Results

Among 2572 renal transplant recipients identified, 24 (0.93%) experienced UC, including 10 men and 14 women of overall mean age of 49.3 ± 11.6 years at transplantation and 53.5 ± 9.5 years at tumor detection. The Chinese traditional herbal intake mainly focused on 2 preparations: Aristolochic acid and rhubarb (the latter was mainly used in patients with chronic renal impairment) in 20 people. There were 21 (87.5%) cases of upper (UTUC) 5 cases of bilateral, and 13 cases of multifocal urinary tract urothelial carcinoma. Four subjects died owing to tumor progression at 4–63 months postoperatively.

Conclusions

UC in renal transplant recipients shared notable characteristics in China with widespread herb intake: UTUC predominance; multifocal and bilateral organ involvement; high rates of recurrence, progression, and dissemination, in contrast with bladder tumor dominance in Western countries. As a consequence, we suggest that bilateral nephroureterectomy should be performed prophylactically in high-risk patients, especially those with a long history of Chinese herb intake. The relationship of rhubarb consumption to UC in renal transplant recipients should be noted and evaluated.     

GBZ 97-2017 《职业性放射性肿瘤判断规范》解析——放射性肿瘤病因概率方法的不确定性

放射性肿瘤病因概率（PC）方法具有先天的不确定性,这是我国国家标准中亟待加强的部分。笔者总结了放射性肿瘤PC方法不确定性的来源和主要内容,以及不确定性的分析和评估的研究现状,并介绍了降低PC方法不确定度的几种措施。     

头孢美法仑的合成及其体外抗肿瘤活性研究

目的设计合成头孢美法仑,并对其进行体外抗肿瘤活性研究。方法以二苯甲酮、美法仑和7-苯乙酰胺基-3-氯甲基头孢烷酸对甲氧基苄酯(GCLE)为原料,经酯化、碘代、偶联、氧化、水解等反应得到目标化合物头孢美法仑,并采用MTT法对其进行体外抗肿瘤活性研究。结果设计并合成了目标产物头孢美法仑,利用MS和1H-NMR确证了结构;体外活性实验中,头孢美法仑在体外基本无毒,酶解后IC50为(101.97±1.705)μmol/L。结论头孢美法仑酶解后能够充分发挥细胞毒作用,而酶解前在体外基本无毒性,为颇具前景的前药,值得进一步研究。     

肠道微生物在放射性肠损伤及其治疗中的研究进展

放射性肠损伤（RIII）是腹盆腔肿瘤放疗中常见的不良反应,严重影响着癌症患者的后续治疗计划和幸存者的生活质量,其患病人数已远超炎症性肠病,亟需有效的防治措施。已有大量研究结果证明,RIII与肠道微生物群失调相关,而粪菌移植（FMT）可以帮助患者恢复肠道微生物群的丰度和多样性,可以作为RIII治疗中的潜在方法。笔者着重综述了肠道微生物在RIII发生和发展过程中的作用及其机制,以及FMT在RIII治疗中的应用。