TWNK基因突变致慢性眼外肌麻痹一家系的临床及遗传学分析

慢性进行性眼外肌麻痹是线粒体病的一种表型,以上睑下垂或眼球活动障碍为特征。该文报道一个TWNK基因突变导致的线粒体病家系的临床和遗传学分析。先证者为32岁女性,因“双眼睑下垂10余年”就诊于河北医科大学第三医院神经肌肉病科,仅表现为眼睑下垂、轻度眼外肌麻痹。临床诊断为“慢性进行性眼外肌麻痹”。其家族中也存在类似病例。为明确致病基因,对先证者进行高通量测序及致病变异筛查。根据临床表型与基因测序结果,确定了TWNK基因的一个杂合突变位点(c.1411T>G,p.Y417D)作为候选致病基因。进一步采用Sanger测序法对先证者及其家系成员进行验证,确认了该突变位点的存在。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,该变异判定为致病变异(PVS1+PM2+PP3),且该位点在国内尚无报道。该研究不仅拓展了TWNK基因的变异谱,还为线粒体病家系的遗传咨询与分子诊断提供了参考依据。

抗GQ1b、GT1a、Sulfatide抗体阳性的类重症肌无力Miller-Fisher综合征1例报告

Miller-Fisher综合征(Miller-Fisher syndrome,MFS)是吉兰-巴雷综合征(Guillain-Barre syndrome,GBS)的一种临床变异型,以共济失调、眼肌麻痹及腱反射消失为主要临床特征,极少出现瞳孔改变和瞳孔对光反射异常,一般无症状波动,部分患者可检测到抗GQ1b IgG抗体阳性。本文报告了1例抗GQ1b、GT1a、Sulfatide抗体阳性的MFS,以波动性眼外肌麻痹起病,伴双侧瞳孔散大、对光反射迟钝及四肢麻木无力,症状少见不典型,临床极易误诊。

复发性痛性眼肌麻痹神经病一例报告并文献复习

目的:探讨复发性痛性眼肌麻痹神经病(RPON)的临床特征,以提高对该病的认识。方法:对南京医科大学附属儿童医院神经内科收治的1例RPON患儿的临床表现及诊治过程进行回顾性分析,并对相关文献进行复习。结果:该患儿反复3次病程,均以头痛及左侧动眼神经麻痹为主诉入院,通过相关检查,排除眼眶、鞍旁及后颅窝的病变,确诊为RPON,予以糖皮质激素等对症治疗后好转出院。文献检索共收集19篇文献,共计26例患儿,其中96.15%患儿有头痛症状,73.08%有伴随症状,所有患儿均表现出眼肌麻痹症状,且均有动眼神经受累,所有病例均接受了增强MRI检查,其中73.08%患儿存在动眼神经增厚、强化。19例接受糖皮质激素治疗的患儿均取得了较好的疗效。结论:RPON是一种以复发性单侧头痛伴同侧眼肌麻痹为特征的罕见病,本病病因未明,典型者幼年开始起病,动眼神经最常受累,部分患者糖皮质激素治疗有效。

2型糖尿病发生与多溴联苯醚暴露的关系及其预测模型构建和评价

目的分析2型糖尿病(T2DM)发生与多溴联苯醚(PBDEs)暴露的关系,通过机器学习方法构建T2DM发生的预测模型并进行评价。方法在NHANES数据库筛选出1425例研究对象,其中非T2DM患者1132例、T2DM患者293例。比较非T2DM患者与T2DM患者的临床资料,取有统计学差异的临床资料进一步进行boruta特征筛选,以明确T2DM发生与PBDEs的关系及其影响因素。将筛选出的T2DM发生影响因素输入R软件,并使用R软件creatDataPartition函数将数据按照80%训练集及20%验证集随机划分。使用逻辑回归、极致梯度提升(XGBoost)、轻量梯度提升、自适应增强、K近邻、朴素贝叶斯及支持向量机等7种算法构建机器学习模型,将训练集输入模型进行训练,将验证集输入模型使用十折交叉验证对进行模型进行内部验证。结合ROC曲线以及曲线下面积(AUC)对模型进行评价,选择新疆医科大学一附院内分泌科就诊的成人T2DM患者71例及健康体检者100例对效能最好的预测模型进行外部验证。使用SHAP工具分析高效能预测模型的可解释性,判断模型在决策过程中各个特征的重要性。结果T2DM患者BMI、腰围、受教育程度、有糖尿病家族史比例、血清高密度脂蛋白及血清BDE-28、BDE-47、BDE-99、BDE-183、BDE-209浓度均高于非T2DM患者(P均<0.05),Boruta特征筛选出腰围、BMI、糖尿病家族史及血清BDE-47、BDE-99、BDE-28、BDE-209、BDE-183作为T2DM发生的影响因素纳入机器学习算法建立T2DM发生的预测模型。在训练集及验证集的内部验证中,XGBoost模型AUC值均最高,且准确度、Kappa值、灵敏度及特异度均位于前列,故选择XGBoost模型作为高效能预测模型。外部验证结果显示,XGBoost模型的准确度为0.702、灵敏度为0.549、特异度为0.787、AUC(95%CI)为0.674(0.575~0.773)。SHAP工具对XGBoost模型的预测情况进行解释性分析结果显示,腰围、血清BDE-47为最重要的预测特征,同时血清BDE-99、BDE-209及BMI、糖尿病家族史在模型中具有较高的重要性,而血清BDE-28、BDE-183在模型中重要性相对较低。结论血清BDE-47、BDE-99、BDE-28、BDE-209、BDE-183为T2DM发生的独立影响因素,基于血清PBDEs及腰围、BMI、糖尿病家族史建立的XGBoost模型对T2DM发生的预测效能较高,在T2DM发生的预测方面具有一定价值。

中国枝角类低额溞属一新记录——密刺低额溞Simocephalus congener(Koch,1841)（英文）

The genus Simocephalus Schoedler 1858,a large,nonpelagic daphniidae,are abundant in the littoral zone,expecially with submerged aquatic vegetation in freshwater bodies all over the world.More than 63 specific and subspecific names have been proposed.But in the recent research,all of them were divided into 4 subgenus and regarded as 20valid names[1].

孕早期静脉导管血流频谱参数颈项透明层及心轴对胎儿先天性心脏畸形的预测价值

目的探讨孕早期脐静脉导管(UVC)血流频谱参数、颈项透明层(NT)及心轴对胎儿先天性心脏畸形(CHD)的预测价值。方法将2021年5月至2023年5月我院收治的106例诊断为CHD胎儿的孕妇为研究组、同期胎儿健康的80名孕妇作为对照组,均行UVC彩色多普勒超声检查,比较2组基线资料、UVC血流频谱参数[心室收缩期峰值速度(S)、心室舒张期峰值速度(D)、心房收缩期峰值速度(a)、A波最大速度(Tamax)、搏动指数(PI)]、NT厚度、心轴角度。Logistic多因素回归分析法明确影响胎儿CHD的危险因素,据此建立预测模型并绘制受试者工作特征曲线(ROC)评估其效能。结果2组年龄、UVC检查时孕周、体质量指数(BMI)等基线资料差异均无统计学意义(P>0.05)。研究组孕早期UVC血流频谱参数S、D、a、Tamax均低于对照组,PI、NT厚度、心轴角度均大于对照组,组间差异有统计学意义(P<0.05)。Logistic多因素回归分析结果显示:S[P<0.001,OR(95%CI)=1.852(1.584,2.680)]、D[P<0.001,OR(95%CI)=1.887(1.644,2.664)]、a[P<0.001,OR(95%CI)=1.907(1.609,2.782)]、Tamax[P<0.001,OR(95%CI)=2.002(1.827,2.794)]、PI[P<0.001,OR(95%CI)=1.992(1.658,2.674)]、NT厚度[P<0.001,OR(95%CI)=1.892(1.624,2.691)]、心轴角度[P<0.001,OR(95%CI)=1.935(1.650,2.719)]是影响胎儿CHD的独立危险因素。基于上述影响胎儿CHD的孕早期UVC血流频谱参数构建logistic回归预测模型:logistic(P)=-40.125+0.629(S)+0.612(D)+0.644(a)+0.659(Tamax)+0.642(PI)+0.628(NT厚度)+0.650(心轴角度),该模型预测胎儿CHD的灵敏度、特异度、阳性预测值、曲线下面积(AUC)分别为89.5%、79.5%、87.9%、0.882。结论孕早期UVC血流频谱参数、NT、心轴联合预测胎儿CHD的灵敏度、阳性预测值较高,可作为胎儿CHD早期筛查的客观指标。

同位素稀释-高分辨气相色谱/高分辨质谱法测定鱼油中总多氯联苯

多氯联苯是主要的持久性有机污染物分类之一,总多氯联苯是IFOS五星认证中一项重要限制性指标。本文建立了一种同位素稀释-高分辨气相色谱/高分辨质谱测定鱼油中209种多氯联苯总含量的分析方法。鱼油样品经正己烷萃取后,经过浓缩、净化,经过同位素标识过程,使用高分辨气相色谱/高分辨质谱(HRGC-HRMS)对目标物进行测定。鱼油中总多氯联苯的检出限为1.4 ng/g,定量下限为5.4 ng/g。

线粒体疾病相关视神经病变

线粒体疾病是主要累及全身多系统且临床表现各异的线粒体能量代谢耗竭疾病,其中眼部可单独受累,尤其是视神经病变可为其唯一表现,或是各种综合征的受累器官之一。临床最常见的线粒体相关视神经病变为Leber遗传性视神经病变和常染色体显性遗传性视神经萎缩。随着基因检测技术的发展,越来越多的线粒体基因突变类型及包括视神经萎缩的各种表型已被认识,例如MELAS脑病、Leigh综合征、Wolfram综合征、Charcot-Marie-Tooth病等。本文主要聚焦包括Leber遗传性视神经病变在内的各种线粒体疾病及其综合征的眼部表现,尤其是视神经病变,通过典型的临床特征及针对性的基因检测手段拓展神经眼科医师对视神经萎缩性疾病的认识,有利于对该类疾病的精准诊疗。

Occurrence and congeners specific of poiychlorinated biphenyls in agricultural soils from Southern Jiangsu, China

A total of 198 agricultural soil samples were collected from Zhangjiagang and Changshu in Southern Jiangsu for analysis of 13 polychlorinated biphenyls （PCBs） in order to assess the levels of pollution, sources, area distribution, and potential risk for the environment. All methods were rigorously tested and an adequate quality control was ensured. Only one site had no PCBs residues, and the highest total PCBs concentration in the surface soils was 32.83 ng/g. The average concentration in all the soil samples was 4.13 ng/g, signaling low-level pollution. Tetra-, penta-, and hexa-chlorinated biphenyls were dominant species in soil samples, accounting for more than 75% of ∑PCBs in the soil samples. PCB118 was the most abundant congener in all the samples. The PCB118 was about 20% of ∑PCBs. The soil organic matter content showed only a weak correlation with the levels of all PCB congeners, in which a better correlation was noted for the more volatile lighter PCB congeners than for the heavier homologues. To a certain extent, the sources and land use seemed to influence the levels of PCBs.

Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata

In the current study, the alopecia areata gene was introduced into the C57BL/6 （B6） mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AAtJmice （named B6.KM-AA） was verified using microsatellites. The gross appearance, growth characteristics, pathological changes in skin, and major organs of B6.KM-AA mice were observed. Counts and proportions of CD4＋ and CD8＋ T lymphocytes in peripheral blood were determined by flow cytometry. Results show that congenic B6.KM-AA mice were obtained after 10 generations of backcrossing/intercrossing. B6.KM-AA mice grew slower than B6 control mice and AA skin lesions were developed by four weeks of age. The number of hair follicles was reduced, but hair structures were normal. Loss of hair during disease progression was associated with CD4＋ and CD8＋ T lymphocytes infiltration peri- and intrahair follicles. No pathological changes were found in other organs except for the skin. In the peripheral blood of B6.KM-AA mice, the percentage of CD4＋ T cells was lower and percentage of CD8＋ T cells higher than in control mice. These findings indicate that B6.KM-AA mice are characterized by a dysfunctional immune system, retarded development and T-cell infiltration mediated hair loss, making them a promising new animal model for human alopecia areata.

Antiproliferative and apoptosis-inducing potential of 3β-hydroxy-△5-steroidal congeners purified from the soft coral Dendronephthya putteri

The exploration and identification of antiproliferative phytochemicals have received increased attention in medicinal chemistry. In particular, research focused on the toxicology of marine natural products has increased in recent years. Terpenoids, among many secondary metabolites, have been demonstrated to act as effective anticancer agents. Soft corals, a group of marine invertebrates, produce a variety of terpenoids with biofunctional properties. The current study presents the extraction, purification, and identification of sterol congeners from the soft coral Dendronephthya putteri. The method involves 50% chloroform-methanol extraction, polar column fractionation, and analysis through GC-MSn. Dose-dependent antiproliferative activity was observed within the sterol-rich fraction (DPCMH 2-4), which consisted of 3β-hydroxy-Δ5-steroidal congeners. This fraction inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 25.27±1.43 and 22.81±0.15 μg/mL, respectively. Apoptotic body formation, DNA damage, cell cycle arrest, and apoptotic cell signaling pathway activation were also observed, reinforcing the dose-dependent antiproliferative and apoptosis-inducing activity of 3β-hydroxy-Δ5-steroidal congeners. To our knowledge, this is the first report of anticancer agent identification from the soft coral D. putteri. Based on the observations, these steroidal congeners are promising candidates for the development of anticancer drugs.

Feasibility of Trace Alcohol Congener Detection and Identification Using Laser-Induced Breakdown Spectroscopy

In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy （LIBS）. In the scheme, an intensive pulsed laser is used to break down trace alcohol samples and the optical emission spectra of the induced plasma are collected for the detection and identifq ication of alcohol molecules. In order to prepare trace alcohol samples, pure ethanol or methanol is bubbled by argon carrier gas and then mixed into matrix gases. The key issue for the scheme is to constitute indices from the LIBS data of the alcohol samples. Two indices are found to be suitable for alcohol detection and identification. One is the emission intensity ratio （denoted as H/C） of the hydrogen line （653.3 nm） to the carbon line （247.9 nm） for identification and the other is the ratio of the carbon line （as C/Ar） or the hydrogen line （as H/Ar） to the argon lines （866.7 nm） for quantitative detection. The calibration experiment result shows that the index H/C is specific for alcohol congeners while almost being independent of alcohol concentration. In detail, the H/C keeps a specific constant of 34 and 23 respectively for ethanol and methanol. In the meanwhile, the C/Ar and H/Ar indices respond almost linearly to the alcohol concentration below 1300 ppm, and are therefore competent for concentration measurement. With the indices, trace alcohol concentration measurement achieves a limit of 140 ppm using a laser pulse energy of 300 mJ.

Saline Stress Response of Plantlets of Common Wheat （Triticum aestivum） and Its Wild Congeners

The aim of this work was to study the reactions of wheat （T. aestivum L.） and its wild congeners under salt stress. Physiological mechanisms that underlie traits for salt tolerance plantlets have been used to test some wheat species and to identify sources of salty tolerance. Stress conditions were founded by means of exposure of the plantlets in NaCI water solution, 1.68% that demonstrably differentiates the samples by growth parameters. Under laboratory conditions the ability of seedlings to bear a significant shortage of water, their ability to accumulate biomass, changing the parameters of linear growth processes and changes in water content in leaves and roots of seedlings under stress was determined. Interest is also the rate of growth of root fibrils in saline conditions. These experiments allowed to provide a comprehensive diagnosis of studied forms of wheat and make an initial opinion on their salt tolerance. Different features of abiotic stress responses of some wheat species at the early stages of development were shown that testifies necessi~ of great number of approaches at selection of genetic material for improvement of modern wheat eultivars. This work is the first phase of research for practical breeding.

A case of polymyositis with ophthalmoplegia Laboratory examinations

OBJECTIVE： Polymyositis （PM） mainly involves proximal limb and trunk muscles. Ocular muscles are not affected, except in rare cases with both PM and myasthenia gravis （MG）. Thus, the results of laboratory examinations in such a patient deserve to be reported. METHODS： To analyze the clinical, imaging and pathology datas on a 65-year-old woman patient with PM with complex symptoms, who presented mainly ophthalmoplegia. The patient consented to all examinations and the hospital Ethics Committee approved the study. The laboratory examinations included creatine kinase （CK）, ENA, tumor marker, function of thyroid, cranial MRI, and electromyogram （EMG）. Biopsy of the left quadriceps femoris was performed, frozen specimens were stained with hematoxylin and eosin, ATPase, NADH tetrazolium reductase, periodic acid Schiff, oil red O, modified Gomory trichrome and MHC-I, to investigate the pathology of muscle fibers RESULTS： Laboratory results showed： CK, 108.32μ kat/L; antinuclear antibody： （＋）; ENA, （-）; tumor marker, （-）; normal thyroid function, MRI showed no abnormal signals in brain and extraocular muscles. Electromyography of the bilateral deltoid, biceps brachii, musculus quadriceps fexoris, anterior tibialis showed fibrillation potentials, positive potentials and short-duration, small-amplitude polyphasic potentials on voluntary movements with a full interference pattern on mild exertion. Repetitive stimulation did not result in any increment or decrement in these potentials. A muscle biopsy of the left quadriceps femoris showed many small round muscle fibers without peripheral bundle distribution and apparent myofiber degeneration, necrosis and phagocytosis. There were several focal lymphocyte infiltrations. MHC-I immunohistochemical staining was positive in most fibers revealing inflammatory infiltration of normal fibers with MHC-I expression. CONCLUSION： This patient showed increased CK, typical triad of myopathy in EMG, and apparent degeneration and necrosis in biopsy of quadriceps femoris. Therefore, the diagnosis of PM and involvement of extraocular muscles were definite.

Prepulse inhibition (PPI) of tactile startle response in recombinant congenic strains of mice:QTL mapping and comparison with acoustic PPI

Prepulse inhibition （PPI） of the startle response is a psychophysiological measure of sensorimotor gating believed to be cross-modal between different sensory systems. We analyzed the tactile startle response （TSR） and PPI of TSR （tPPI）, using light as a prepulse stimulus, in the mouse strains A/J and C57BL/6J and 36 recombinant congenic strains derived from them. Parental strains were significantly different for TSR, but were comparable for tPPI. Among the congenic strains, variation for TSR was significant in both genetic backgrounds, but that of tPPI was significant only for the C57BL/6J background. Provisional mapping for loci modulating TSR and tPPI was carried out. Using mapping data from our previous study on acoustic startle responses （ASR） and PPI of ASR （aPPI）, no common markers for aPPI and tPPI were identified. However, some markers were significantly associated with both ASR and TSR, at least in one genetic background. These results indicate cross-modal genetic regulation for the startle response but not for PPI, in these mouse strains.

False negative diffusion weighted imaging in an acute onset double vision patient with isolated internuclear ophthalmoplegia from ischemic origin

Dear Editor, A-72-year-old male with medical history of hypertension admitted with acute onset double vision.On neurological examination,right eye could not adduct whereas nystagmus occurs on the left eye abduction.Cranial diffusion weighted imaging (DWI) was in normal ranges.Based on the negative DWI result and atypical clinical presentation for stroke,third nerve paly was considered in the forefront and the patient was planned to be discharged with suggestion of ophthalmology outpatient visit.However,following neurology evaluation,the diagnosis of left internuclear ophthalmoplegia (INO) was favored.

Early-onset ophthalmoplegia,cervical dyskinesia,and lower extremity weakness due to partial deletion of chromosome 16:A case report

BACKGROUND We explored the genotype-phenotype correlation of the novel deletion 16p13.2p12.3 in an 8-year-old child with progressive total ophthalmoplegia,cervical dyskinesia,and lower limb weakness by comparing the patient’s clinical features with previously reported data on adjacent copy number variation(CNV)regions.CASE SUMMARY Specifically,we first performed whole-exome sequencing,CNV-sequencing,and mitochondrial genome sequencing on the patient and his parents,then applied“MitoExome”(the entire mitochondrial genome and exons of nuclear genes encoding the mitochondrial proteome)analysis to screen for genetic mitochondrial diseases.We identified a de novo 7.23 Mb deletion,covering 16p13.2p12.3,by both whole-exome sequencing and CNV sequencing.We also detected 16p13.11 in the deleted region,which is the recurrent distinct region associated with neurodevelopmental disorder.However,the patient only displayed features of progressive total ophthalmoplegia,cervical dyskinesia,and weakness in his lower limbs without neurodevelopmental disorder.The“MitoExome”sequencing was negative.Brain magnetic resonance imaging revealed non-specific sporadic changes in the occipital parietal lobe and basal ganglia.CONCLUSION Taken together,these results indicated that 16p13.2p12.3 deletion causes a syndrome with the phenotype of early-onset total ophthalmoplegia.The“MitoExome”analysis is powerful for the differential diagnosis of mitochondrial diseases.We report a novel copy number variant in this case,but further confirmation is required.

模拟氮沉降对鬼针草及其近缘本地植物的影响

【目的】理解氮素增加对入侵植物与近缘共存本地植物生长和竞争的影响,可为预测全球氮沉降背景下入侵植物的风险评价和本地植物的保护提供依据。【方法】为模拟氮沉降,设置对照(无氮添加)、低氮(1 g·m^(-2)·a^(-1))和高氮(5 g·m^(-2)·a^(-1))添加3种处理,将入侵植物鬼针草及其近缘共存的本地植物金盏银盘分别单种和混种,比较它们在各处理下的生长(株高、分枝数和生物量等)和竞争[相对优势度指数(RDI)与相对互作强度指数(RII)]情况。【结果】无论有无竞争,高氮添加均显著增加鬼针草的生物量,降低其根冠比;无竞争时,高氮添加还显著增加其株高和分枝数。但高氮添加仅显著增加金盏银盘无竞争时的生物量。在所有氮处理下,鬼针草的RDI和RII均显著大于金盏银盘。高氮添加显著增加鬼针草的RDI,但其RII在所有氮处理间无显著差异;高氮添加显著降低金盏银盘的RDI和RII。【结论】高氮更利于鬼针草的生长,其在所有氮素处理下均有较强的竞争力和竞争耐受性,且高氮处理下竞争力更强。因此,全球氮沉降增加会加剧鬼针草对近缘本地植物的竞争抑制和入侵风险。

Adenosine amine congener ameliorates cisplatin-induced hearing loss

AIM: To investigate a novel pharmacological intervention to mitigate cisplatin ototoxicity using a selective adenosine A1 receptor agonist adenosine amine congener(ADAC).METHODS: Male Wistar rats(8-10 wk) were exposed to a two-cycle cisplatin treatment similar to clinical course of cancer chemotherapy. Each cycle comprised 4 d of intraperitoneal cisplatin injections(1 mg/kg twice daily) separated by 10 d of rest. ADAC(100 μg/kg) or drug vehicle solution(control) was administered intraperitoneally for 5 d at 24 h intervals during the second cisplatin cycle(Regime 1), or upon completion of the cisplatin treatment(Regime 2). Hearing thresholds were measured using auditory brainstem responses(ABR) before cisplatin administration(baseline) and 7 d after the end of cisplatin treatment. Histological analysis of cochlear tissues included hair cell counting and qualitative assessment of apoptosis using terminal deoxynucleotidyl transferase mediated d UTP nick end labelling(TUNEL) staining.RESULTS: ABR threshold shifts in cisplatin-treated Wistar rats ranged from 5-29 d B across the frequency range used in the study(4-24 k Hz). Higher frequencies(16-24 k Hz) were mostly affected by cisplatin ototoxicity(mean threshold shift 25-29 d B). ADAC treatment during the second cisplatin cycle reduced cisplatininduced threshold shifts by 12-16 d B(P < 0.01) at higher frequencies compared to control vehicle-treated rats. However, the treatment was ineffective if ADAC administration was delayed until after the completion of the cisplatin regime. Functional recovery was supported by increased survival of hair cells in the cochlea. Qualitative analysis using TUNEL staining demonstrated reduced apoptosis of the outer hair cells and marginal cells in the stria vascularis in animals treated with ADAC during the second cisplatin cycle.CONCLUSION: A1 adenosine receptor agonist ADAC mitigates cisplatin-induced cochlear injury and hearing loss, however its potential interference with antineoplastic effects of cisplatin needs to be established.

A MILD AND REGIOSPECIFIC OXIRANE RING OPENING TO PRECURSORS FOR PROSTANOID CONGENERS

A stereoselective and regiospecific synthesis of procursors(2),(4),(6)and(7)of prostacyclin analogues from 2,3-epoxylbicyclo[3.2.0]hept-6-one(1)are described.