HIV/AIDS患者结核潜伏感染的影响因素研究

背景 结核病是导致人免疫缺陷病毒/获得性免疫缺陷综合征（HIV/AIDS）患者死亡的首要原因，而HIV感染也是导致结核潜伏感染（LTBI）发展为结核病的主要危险因素。因此，对HIV/AIDS患者进行LTBI筛查和治疗是预防该类人群结核病的发生从而减少其死亡的重要举措。 目的 对宁夏回族自治区银川市市区内HIV/AIDS患者进行LTBI筛查，并分析其影响因素，识别高危人群，为HIV/AIDS患者结核病的预防性治疗提供科学依据。 方法 选取2021年3—8月于宁夏回族自治区银川市市区内定点管理单位治疗的546例HIV/AIDS患者为研究对象。通过现场问卷调查及查阅患者管理档案的方式收集HIV/AIDS患者的一般资料，其中一般人口学特征包括性别、年龄、民族、学历、婚姻状况、家庭人均年收入、职业类型、体质指数（BMI）、吸烟情况、饮酒情况等；临床资料包括慢性病患病情况、与结核病患者密切接触情况、HIV/AIDS确诊时长、抗病毒治疗时长、合并其他感染情况、近期CD4+ T淋巴细胞计数（CD4）等。通过结核菌素皮肤试验（TST）对研究对象进行LTBI筛查，根据TST结果将546例HIV/AIDS患者分为非LTBI组（TST阴性413例）和LTBI组（TST阳性133例）。比较两组患者的一般资料，采用多因素Logistic回归分析探讨HIV/AIDS患者发生LTBI的影响因素，并利用R软件建立限制性立方样条模型拟合CD4与LTBI风险之间的量效关系。 结果 银川市市区内HIV/AIDS患者的TST阳性率为24.4%。已婚〔OR=0.544，95%CI（0.321，0.922），P<0.05〕是HIV/AIDS患者发生LTBI的保护因素；吸烟〔OR=1.919，95%CI（1.213，3.037），P<0.05〕、与结核病患者有过密切接触〔OR=11.100，95%CI（2.889，42.648），P<0.05〕是HIV/AIDS患者发生LTBI的危险因素。限制性立方样条模型拟合结果显示，HIV/AIDS患者的CD4与LTBI风险呈近似"n"形的非线性关系（非线性检验χ2=29.080，P<0.001）。 结论 应重点关注HIV/AIDS患者中未婚、吸烟、与结核病患者有过密切接触人群LTBI的发生情况，并及时进行预防性治疗；对于CD4较低的患者，建议采用多种方法进行LTBI筛查。     

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.