Purification and enzymatic activity of an NADH-fumarate reductase and other mitochondrial activities of Leishmania parasites

A 65 kD membrane-associated NADH-fumarate reductase subunit, which has a molecular weight similar to that of one of the enzyme subunits from bacteria, was purified from Leishmania donovani promastigotes. NADH-fumarate reductase and other mitochondrial enzymatic activities of L. major and L. donovani promastigotes and amastigotes were investigated. The presence of NADH-fumarate reductase was demonstrated in digitonin-permeabilized L. major promastigotes and mitochondria of L. major and L. donovani promastigotes and amastigotes. The activity of solubilized NADH-fumarate reductase was measured in L. major and L. donovani promastigotes. Succinate exhibited a clear concentration-dependent inhibitory effect on fumarate reductase, whereas fumarate also exhibited a clear concentration-dependent inhibitory effect on succinate dehydrogenase. The data indicate that fumarate reductase is an obligatory component of the respiratory chain of the parasite. Since the enzyme is an important component in the intermediate metabolism in the Leishmania parasite and is absent in mammalian cells, it could be a potential target for antileishmanial drugs.     

Potential Role of Probiotics in Ameliorating Psoriasis by Modulating Gut Microbiota in Imiquimod-Induced Psoriasis-Like Mice

Psoriasis is an immune-mediated systemic disease that may be treated with probiotics. In this study, probiotic strains that could or could not decrease interleukin (IL)-17 levels were applied to imiquimod (IMQ)-induced psoriasis-like mice via oral administration. Bifidobacterium adolescentis CCFM667, B. breve CCFM1078, Lacticaseibacillus paracasei CCFM1074, and Limosilactobacillus reuteri CCFM1132 ameliorated psoriasis-like pathological characteristics and suppressed the release of IL-23/T helper cell 17 (Th17) axis-related inflammatory cytokines, whereas B. animalis CCFM1148, L. paracasei CCFM1147, and L. reuteri CCFM1040 neither alleviated the pathological characteristics nor reduced the levels of inflammatory cytokines. All effective strains increased the contents of short-chain fatty acids, which were negatively correlated with the levels of inflammatory cytokines. By performing 16S rRNA gene sequencing, the diversity of gut microbiota in psoriasis-like mice was found to decrease, but all effective strains made some specific changes to the composition of gut microbiota compared to the ineffective strains. Furthermore, except for B. breve CCFM1078, all other effective strains decreased the abundance of the family Rikenellaceae, which was positively correlated with psoriasis-like pathological characteristics and was negatively correlated with propionate levels. These findings demonstrated effects of strain-specificity, and how probiotics ameliorated psoriasis and provide new possibilities for the treatment of psoriasis.     

无创高频振荡通气在极低出生体重早产儿呼吸窘迫综合征初始呼吸支持治疗中的应用

目的探讨经鼻无创高频振荡通气(NHFOV),在呼吸窘迫综合征(RDS)极低出生体重早产儿初始呼吸支持治疗的临床疗效。 方法选择2018年2月至2020年4月,于徐州市中心医院新生儿重症监护病房(NICU)治疗的92例RDS极低出生体重早产儿为研究对象。采用随机数字表法,将其分为NHFOV组(n＝48,采取NHFOV治疗)及经鼻持续气道正压通气(NCPAP)组(n＝44,采取NCPAP治疗)。对2组RDS极低出生体重早产儿一般临床资料,无创通气治疗前、后动脉血气分析指标,疗效,呼吸支持治疗相关并发症发生率及患儿死亡率,采用成组t检验、χ²检验及Mann-Whitney U检验进行统计学比较。本研究经徐州市中心医院医学伦理委员会审核批准(审批文号：XZXY-LJ-20170328-006),并且与患儿监护人均签署临床研究知情同意书。 结果①一般临床资料比较：2组RDS极低出生体重早产儿的性别、出生胎龄与体重及生后1、5 min Apgar评分,入院日龄及分娩前24 h母亲糖皮质激素使用率等一般临床资料比较,差异均无统计学意义(P>0.05)。② 2组RDS极低出生体重早产儿动脉血气分析指标组间比较：NHFOV组RDS极低出生体重早产儿无创通气治疗后1 h、24 h动脉血二氧化碳分压(PaCO₂)分别为(45.8±6.5) mmHg(1 mmHg＝0.133 kPa)及(40.8±4.7) mmHg,均显著低于NCPAP组的(49.3±5.7) mmHg及(44.2±5.2) mmHg;治疗后1 h、24 h动脉血氧分压(PaO₂)与吸入氧浓度分数(FiO₂)比值(P/F)分别为(198.8±30.5) mmHg及(215.1±32.1) mmHg,均显著高于NCPAP组的(176.4±28.1) mmHg及(190.0±29.7) mmHg,并且上述差异均有统计学意义(t＝2.809、3.301、3.663、3.881,P＝0.003、<0.001、<0.001、<0.001)。③2组动脉血气分析指标分别进行组内比较均为：无创通气治疗后24 h的pH值及治疗后1、24 h的PaCO₂水平,均较治疗前改善,而且治疗后24 h的P/F值高于治疗后1 h,并且差异均有统计学意义(P<0.05)。④无创通气疗效比较：NHFOV组RDS极低出生体重早产儿无创通气治疗后,肺表面活性剂(PS)使用率及有创机械通气率(22.9%、6.3%),均显著低于NCPAP组(45.5%、20.5%),并且差异均有统计学意义(χ²＝5.219、4.084,P＝0.022、0.043)。2组RDS极低出生体重早产儿无创通气时间、柠檬酸咖啡因使用率、频繁呼吸暂停发生率及总用氧时间比较,差异均无统计学意义(P>0.05)。⑤2组RDS极低出生体重早产儿鼻损伤、肺气漏、新生儿坏死性小肠结肠炎(NEC)、Ⅲ~Ⅳ级脑室内出血(IVH)、早产儿视网膜病(ROP)(≥Ⅱ期)及支气管肺发育不良(BPD)发生率,以及患儿死亡率比较,差异均无统计学意义(P>0.05)。 结论与NCPAP比较,NHFOV用于RDS极低出生体重早产儿初始呼吸支持治疗,能改善氧合、减少二氧化碳(CO₂)潴留、减少有创机械通气及PS使用,同时不增加呼吸支持治疗相关并发症发生。     

脑星形细胞瘤p16基因缺失及5'CpG岛甲基化检测

目的探讨p16基因异常与脑星形细胞瘤发生、发展的关系。方法利用PCR及PCR-based甲基化技术检测了56例不同级别的脑星形细胞瘤组织p16基因缺失及5'CpG岛甲基化状况。结果18例高病理级别的脑星形细胞瘤发生了p16基因缺失,而低病理级别的脑星形细胞瘤无一例发生缺失（P<0.05）;6例脑星形细胞瘤发生了p16基因5'CpG岛甲基化。结论p16基因失活可能参与脑星形细胞瘤的病理发生、恶性进展。p16基因纯合缺失是p16基因失活的主要机制。     

A Multilevel Intervention to Increase HPV Vaccination among Asian American Adolescents

Human papillomavirus (HPV) is the most common sexually transmitted infection in the US. HPV vaccine is a viable source of prevention against high-risk strains that are likely to cause cancer. However, particularly among racial and ethnic minorities such as Chinese Americans, HPV vaccination rates are suboptimal. The goal of this study was to evaluate the effect of a culturally tailored intervention on HPV vaccine uptake in Chinese Americans. We designed and implemented a multilevel longitudinal pilot study to examine the efficacy of the HPV intervention among Chinese American parents/guardians. We recruited 180 participants from federally qualified health center and community-based clinics that serve predominantly low-income Chinese Americans in Philadelphia. Participants were randomized into an intervention group (n?=?110) or a control group (n?=?70). The intervention group received an HPV specific intervention, while the control group received a general health intervention. The primary outcome was medical record-confirmed receipt of first shot and completion of HPV vaccine within six months of receiving the interventions. Repeated measure ANOVA was utilized to examine the intervention effect on knowledge between intervention and control groups. Knowledge differed significantly, with participants in the intervention group demonstrating the greatest improvement following the intervention. A multivariable logistic regression was used to examine the association between HPV vaccine initiation and study group assignment. There was a significant effect of provider recommendation, parent’s gender, and health insurance status on HPV vaccine uptake. This study demonstrated positive impact of a culturally tailored intervention on HPV vaccination uptake among Chinese Americans.

     

阿狄森病患者外周血白细胞性激素受体的改变及意义

应用放射配体结合法检测１６例阿狄森病患者外周血白细胞雌激素受体（ＥＲ）和雄激素受体（ＡＲ），同时用放射免疫分析检测血浆雌二醇（Ｅ２）和睾酮（Ｔ）水平，结果如下：１）阿狄森病患者血浆Ｅ２高于对照组，但无统计学意义，血浆Ｔ无明显改变，Ｅ２／Ｔ比值明显高于对照组（Ｐ〈０．０５）；２）阿狄森病患者白细胞ＥＲ明显高于对照组（Ｐ〈０．０１），ＡＲ轻度降低（Ｐ〉０．０５），ＥＲ／ＡＲ比值明显高于对照组（Ｐ〈０．     

非细胞体系核重构过程的超微结构研究

用电镜观察Lambda DNA与非洲爪蟾卵提取物在非细胞体系内的核重构,发现Lambda DNA首先诱导形成类染色质结构,膜泡、核孔复合体围绕这一结构组装成双层核膜,同时类染色质也随着核膜的装配,表现出从致密凝聚到呈现松散均匀分布的变化。有工作表明,在由染色质诱导的核重构过程中,或者是膜泡先与染色质结合,然后有核孔出现,或者是核孔物质先与染色质作用,膜泡通过结合核孔物质形成双层核膜。我们观察由外源DNA诱导的核重构过程,则发现膜泡与核孔复合体先分别独立地与类染色质结构相互作用,然后核孔复合体再镶嵌到双层核膜中。     

病毒性肝炎的基因治疗及其伦理问题

病毒性肝炎迄今仍无特异有效的治疗药物和方法.而近年发展起来的基因治疗可能将是一种有效的治疗方法,并在体外和实验动物中取得了相当的成功,但若应用于人体还需解决很多问题尤其是伦理学问题.     

粒单系白血病原始细胞表达血小板特异性抗原与周期蛋白D3异常表达关系的研究

目的 :探讨急性单核细胞白血病原始细胞表达血小板特异性抗原的机制。方法 :分离外周血或骨髓单个核细胞 ,采用常规染色和普通细胞化学染色观察其形态学特性 ,采用流式细胞仪双荧光分析免疫表型 ,单荧光胞浆蛋白标记分析周期蛋白表达和免疫印迹进一步证实周期蛋白 D3的表达情况。采用周期蛋白和 DNA双标记分析周期蛋白 D3表达与细胞周期的关系。结果 :白血病原始细胞中 CD1 3 HL A- DR 细胞为 94.6 9% ,CD1 3 CD34 细胞为 96 .86 % ,CD41 a CD34 细胞为 41.6 0 % ,CD1 3 CD41 a 细胞为 40 .0 0 % ,免疫印迹和流式细胞仪单参数分析证实周期蛋白 D3表达明显升高 ,周期蛋白 D3阳性细胞在细胞周期各时段所占的比例分别为 :G1 期 5 2 .10 % ,S期9.90 % ,G2 M期 38.0 0 %。结论 :周期蛋白 D3的异常表达导致单核系白血病细胞表达血小板特异性抗原 ,同时也可能在白血病的发生中起重要作用。     

白血病患者骨髓细胞中载脂蛋白E的表达

目的：探讨白血病患者骨髓细胞中载脂蛋白Ｅ（ＡｐｏＥ） 的表达。方法：应用免疫组化ＳＰ法检测正常人骨髓细胞及白血病患者骨髓细胞ＡｐｏＥ的表达,正常人骨髓涂片６ 例,急性淋巴细胞性白血病１３ 例,急性髓性细胞白血病２９ 例。结果：ＡｐｏＥ在所检正常人骨髓涂片中均表达（ 着色程度＋ ～《） ,骨髓细胞表达阳性率为２０％ ±４％ 。急性淋巴细胞白血病原始细胞中不表达ＡｐｏＥ,急性髓性细胞白血病原始细胞不同程度表达ＡｐｏＥ,其中急性粒细胞白血病部分分化型着色＋ ,原始细胞表达阳性率为７０％ ±３２ ％ ,急性早幼粒细胞白血病着色《～》,阳性率８９％ ±４ ％ ,急性粒单细胞白血病着色（＋ ～《）,阳性率５０％ ±３％ ,急性单核细胞白血病着色《,阳性率１５ ％ ±４ ％ 。结论：ＡｐｏＥ可作为鉴别髓性和淋巴细胞白血病的一项指标