In silico screening and analysis of single-nucleotide polymorphic variants of the ABCC2 gene affecting Dubin–Johnson syndrome

Background and Study AimsDubin–Johnson syndrome (DJS) is a benevolent genetic disorder of the liver with autosomal inheritance. It is a rare disorder characterized by an increase in conjugated bilirubin and anomaly in coproporphyrin clearance. DJS is caused by deleterious mutations in the ABCC2 gene. A polymorphism in the ABCC2 gene causes malfunctions in its ability to regulate the efflux of different organic anions, such as bilirubin, from hepatocytes to the canaliculi. Multidrug resistance protein 2 (MRP2) encoded by the ABCC2 gene is one of the main regulators of the export of bilirubin to respective sites. ABCC2 gene mutations have widely drawn attention in the pathology of DJS in various populations.Patients and MethodsThe ABCC2 gene was subjected to the National Center for Biotechnology Information (NCBI) database in 2020, and non-synonymous single-nucleotide polymorphisms (nsSNPs) and variants in untranslated regions were studied using different computational servers. SIFT, Protein variation effect analyzer, and PolyPhen-2 were used to retrieve the damaging Single-nucleotide polymorphisms (SNPs); PhD-SNP, SNPs&GO, and Protein Analysis Through Evolutionary Relationships were used to predict the association of nsSNPs with DJS; Mutation3D illustrated the location of variants in the protein; SNAP2, MutPred2, ELASPIC, and HOPE were used to predict the structural and functional effects of these mutations on MRP2; and I-mutant 3.0 and MuPro were used to determine the effects of polymorphism on the function of MRP2.ResultsIn this study, 18,947 SNPs were screened from the NCBI database, followed by a series of refinement of variants using online available servers. We concluded that 41 ABCC2 gene variants are vital etiological candidates for DJS in humans. These 41 variants had highly damaging effects on the MRP2 protein, which may lead to deficient transportation capacity, thereby affecting the efflux of bilirubin across the canalicular membrane.ConclusionIn silico tools are an alternative approach for predicting the target SNPs. Hence, previously unreported variants can be considered strong etiological candidates for diseases related to MRP2.     

2例胰岛素自身免疫综合征临床病例分析

通过回顾分析我院2例确诊为胰岛素自身免疫综合征(IAS)患者的临床资料,并复习相关文献,总结发病机制及治疗方法,探讨IAS患者的临床特点,提高对低血糖症的诊治水平。     

基于贵州省人群队列的代谢综合征发病风险和影响因素分析

目的 探讨代谢综合征（MS）的发病风险和影响因素，为预防MS提供科学依据。方法 采取多阶段整群抽样方法，于2010年建立贵州省人群队列，排除基线MS患者后，共有7 136人进入MS随访队列，收集队列人群基线社会人口学信息、生活行为方式和生理指标，并于2016—2020年进行随访，最终纳入4 754人进行分析。采用COX比例风险模型分析MS的发病风险及其影响因素的HR（95% CI），并计算影响因素的人群归因危险度（PAF%）。同时根据基线人群的MS组分得分建立亚队列，分析亚队列人群MS的影响因素。结果 队列人群累计随访33 424.18人年，中位随访6.57年，新发MS 963人，MS发病密度为28.81/1 000人年。COX回归分析结果显示:年龄45～59岁（HR = 1.53，95%CI:1.32～1.77）、年龄≥60岁（HR = 1.53，95%CI:1.27～1.86）、城市（HR = 1.71，95%CI:1.47～1.99）、吸烟（HR = 1.22，95%CI:1.01～1.48）、每日油摄入＞30 g（HR = 1.16，95%CI:1.01～1.34）、每日盐摄＞6 g（HR = 1.22，95%CI:1.05～1.42）、静态时间≥4 h/d（HR = 1.16，95%CI:1.02～1.32）、超重（HR = 1.66，95%CI:1.44～1.92）、肥胖（HR = 2.27，95%CI:1.71～3.02）、静息心率70～80次/min（HR = 1.32，95%CI:1.11～1.58）和 ＞80次/min（HR = 1.28，95%CI:1.07～1.54)是MS的危险因素，其PAF%分别为17.47%、11.32%、19.52%、5.89%、11.33%、13.66%、7.01%、12.91%、5.30%、17.68%、13.92%，文化程度升高（HR = 0.75，95%CI:0.68～0.83）和饮茶行为（HR = 0.82，95%CI:0.71～0.95）是MS的保护因素，其PAF%分别为16.21%和6.97%。亚队列研究结果与总体结果相似。结论 不健康的生活方式和超重、肥胖、静息心率升高是MS的影响因素，应将中老年人和城市居民作为预防MS的重点人群，采取相应措施控制烟草消费、油盐摄入，维持正常体重和适当心率，提高人群知识水平，保持饮茶行为，预防MS发生。     

When Fryn met Edward: Two rare syndromes in a single patient

A neonate born at our centre was diagnosed as Fryns Syndrome ie congenital diaphragmatic hernia with facial dysmorphism and distal limb anomalies, which is a rare disorder with only a few hundred cases reported till date.With high clinical index of suspicion and further evaluation, the diagnosis was confirmed. The baby was initially stabilized and later underwent repair of the diaphragmatic hernia. Despite best measures, the baby could not be salvaged. When severe, this can be lethal and diagnosis can only be made after autopsy. However, with early suspicion, better modalities of investigations available and improved NICU care, these babies can be salvaged. We report a case of Fryns Syndrome who was incidentally found to have Edward Syndrome as well. Such an extremely rare combination is yet to be reported in medical literature.Also with updated genetic studies, better diagnostics and treatment options coming up in future, there are chances to improve the survivability of these babies. It is prudent to document all such cases to aid in better understanding of the disease process.     

特纳综合征患者骨质疏松的研究进展

特纳综合征(TS)是女性常见的性染色体异常疾病,与多种疾病共存。越来越多的证据表明TS患者有较高的骨质疏松患病率,本文就近年来TS中骨质疏松的危险因素及管理治疗的相关研究进展做一综述。     

Organoids in modelling infectious diseases

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.     

基于代谢组学分析的18-三体妊娠羊水差异代谢物

摘要:目的通过 非靶向代谢组学方法分析18-三体( trisomy 18,T18) 妊娠母体羊水样本,探索其差异代谢物。方法采用病 例-对照研究,以8例18-三体妊娠母体羊水样本为病例组,40例正常胎儿母体羊水样本为对照组,采用气相色谱飞行时间质 谱技术( GC-T0F/MS)检测两组羊水样本。采用主成分分析(PCA)和正交偏最小二乘法判别分析(OPIS-DA)模型分析代谢谱 差异,通过单维统计分析寻找差异代谢物。结果PCA 和OPLS-DA模型分析均显示病例组与对照组之间无明显分离趋势。 通过单维分析在两组间共发现5种差异代谢物,分别为甘油醛、葡萄糖酸、硫酸吲哚酚.磷酸盐和泛酸(P<0.05)。结论羊水 代谢组学证实18-三体妊娠存在多种代谢物水平的差异,为疾病的发生机制的探索提供了更多研究思路。     

Gaslighting in alleged assault ascertained as Munchausen syndrome transcending to malingering in highly counterintuitive self inflicted acid burns

A factitious disorder leading to the self-infliction of highly counter-intuitive burns was diagnosed in a middle-aged female. The injuries were otherwise alleged to have been sustained by assault inflicted upon her by an unknown person. The case was diagnosed by medico-legal interpretation of injuries, in spite of a highly deceptive and concocted history by the patient and her husband. The entity was unique in being associated with magnificent primary, secondary and tertiary gains. The exploitation of the morbid sequel to malinger by the patient, and the involvement of the husband for the prolongation of the illness of his wife for financial gains as gaslighting was highly unusual. The self-infliction of injuries over hands is seen in factitious disorder. However, a combination of a guarded self-immersion of the hands and feet in a corrosive by an illiterate female, followed by malingering to earn livelihood is unprecedented in factitious disorders. The delayed presentation which required amputation of all the limbs to save the life of the patient is a glaring highlight of this case.