HBV-ACLF患者血清miR-122和 HMGB1水平及其与病情、预后的关系

[摘要]　目的　探究HBV相关慢加急性肝衰竭（HBV-related acute-on-chronic liver failure, HBV-ACLF）患者血清中微小核糖核酸（microRNA, miR）-122和高迁移率族蛋白1（high-mobility group box-B1, HMGB1）水平及其与病情、预后的关系。方法　回顾性分析2016年1月—2018年1月我院收治的120例HBV-ACLF患者的一般及临床资料。根据临床结局，将患者分为存活组（53例）和死亡组（67例）。比较2组患者的一般资料、实验室检查指标及血清miR-122、HMGB1水平。多因素Logistic回归分析影响患者预后的因素。Pearson检验分析miR-122、HMGB1水平分别与TBIL、PA、终末期肝病评分模型（the model of end-stage liver disease score, MELD）评分的相关性。ROC曲线分析miR-122和HMGB1水平对患者的死亡预测价值，获得最佳临界值。根据临界值将患者分为A组、B组和C组，用Kaplan-Meier法绘制生存曲线，比较3组患者在3年随访期间的生存率。结果　存活组和死亡组患者的年龄、身体质量指数、并发症、病情分期、MELD评分、ALB、球蛋白、TBIL、ALT、AST、LDH、PT、PTA、HBV DNA、miR-122、HMGB1相比，差异均具有统计学意义（P均＜0.05）。年龄、并发症、病情分期、MELD评分、TBIL、PT、PTA、miR-122、HMGB1均是影响患者预后的危险因素（P均＜0.05）。miR-122、HMGB1水平分别与TBIL、MELD评分呈显著正相关，与PTA呈显著负相关（P均＜0.05）。miR-122和HMGB1预测患者死亡的最佳临界值分别为31.42和14.56 μg/L。A组患者预后3年内生存率显著高于B组和C组（P均＜0.05）。结论　miR-122和HMGB1水平与HBV-ACLF患者的病情和死亡预后密切相关，可间接反映患者的病情严重程度，在HBV-ACLF的诊断及预后中具有重要价值。     

L’expert judiciaire et l’irresponsabilité pénale. Débats et controverses au cours du temps et questions contemporaines

IntroductionSince the creation of the Société Médico-Psychologique, an accumulation of discussions at the national level has resulted in legislative changes, which concern people with mental disorders. Public opinion has now become a stakeholder, prompting us, as judicial experts, to address criminal irresponsibility. The authors wish to give an account of the evolution of the ideas and professional practices in alienism and forensic psychiatry regarding criminal liability, irresponsibility, and the evolution of legislative measures in this realm.MethodsTo do so, they rely on the use of their forensic psychiatric and medico-psychological expertise, which has been effective for many years and remains relevant today, as well as on their clinical and theoretical research activities. The methodology is based on the analysis of language and the critical approach of historical and clinical epistemology.Forensic IssuesThey are examined taking into account the cultural and scientific context from the middle of the 19th century to the beginning of the 21st century. Criminal responsibility and irresponsibility are ancient principles codified in Roman law by Marcus Aurelius and which evolved with the political, social and religious conjunctions of each epoch. Whether the reason given for the recognition of criminal irresponsibility is referred to as madness, degeneration, insanity, dementia, psychic abnormality or discernment, it has always been the subject of research by physicians, alienists, and then psychiatrists. The authors analyze the role of the dissemination of the debates from the creation of the Annales Médico-Psychologiques (in 1843) and of the Société Médico-Psychologique (in 1852), illustrating them with some famous cases in specialized literature. The importance of forensic discussions at the Société Médico-Psychologique animated the end of the nineteenth century and the first part of the twentieth century, contributing to the enrichment of psychiatric semiology and to the opening up of new research, notably methodological. This will lead to an evolution of the conceptions relative to what induces the criminal act and will no longer limit irresponsibility to a diagnosis of insanity or dementia ; the study of psychic functioning will be put forward with the notion of discernment and those of self-control of one's actions. If numerous theoretical debates within the profession have fueled “expert disputes” sometimes disqualifying the role of experts, they remained, however, in the medical and judicial field. Over the past decade, these issues have been broadened to include societal debates around issues related to dangerousness and recidivism. This has become a dominant theme in scientific gatherings, before the eruption into the criminal field, of the increasing role played by victims and victims’ associations. Law No. 92-683 of 22 July 1992 introduced into the Penal Code Article 122-1 (1994 Penal Code) replacing Article 64, by inserting the notions of alteration or abolition of discernment. This distinction has given rise to new difficulties and tensions in expert practice ; the law came into force in 1994. During the 2000s, a series of high-profile homicides involving people with serious mental disorders, sometimes carried out in a recidivist situation, hit the headlines in France. This resulted in a shift in public opinion that led to the law of 25 February 2008 on criminal irresponsibility. The law put an end to the judicial dismissal of cases on the grounds of criminal irresponsibility, by introducing other provisions in the form of security measures (judicial supervision and detention of security). This law creates new interferences between legal procedural issues and psychiatric practice ; it also emphasized the importance of the role of experts by creating new missions, including the expertise of dangerousness. The movement linked to the consideration of the place of victims has been accentuated, both by the objective of obtaining a judgment for the perpetrator of the acts, and by the solicitation of their participation in the successive phases of the procedure. We have recently moved on to questions and controversies about the lack of accountability leading to the law of 24 January 2022. The current article 122 did not specify the origin of the psychic disorder causing the abrogation of discernment, which was interpreted by the Minister of Justice as “a legal void”, which must be “filled with urgency”. Title I states: “Provisions limiting criminal irresponsibility in cases of mental disorder resulting from self-induced psychoactive substances”. All these new provisions, as well as the creation of new incriminations and qualifications, certainly engender debates between magistrates and experts, but they are above all part of a concern of the public authorities about the necessity of setting up “provisions limiting criminal liability in the case of mental disorder”. The interpretation of the contribution of the law to a criminal act remains complex, according to the authors, in terms of psychopathological and etiopathogenic research. Within the context of expert practice, this new law will make it necessary to add new questions for the current missions, and it can only result in an increase in the complexity of these missions and in a risk of confusion in the answers.ConclusionThe authors show that the question of criminal liability does not solicit the same questions and problems in the judicial field (the point of view of the forensic psychiatrist, during the expert examination) or in the societal field with the confrontation with all the representations that are attached both to madness and to the passage to the criminal act, which since the beginning of the twentieth century involves other emerging disciplines. From their point of view, the assertion that a psychic disorder can be of such severity so as to affect the free will and discernment of the perpetrator of a criminal act at the time of the offence, must remain within the domain of psychiatry, even if the new law of 24 January 2022, through several of its provisions, would attempt to eliminate this necessity.     

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

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Growth plate injury of the long bones in treated β-thalassemia

In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50–80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded.     

Droplet digital PCR and qRT-PCR to detect circulating miR-21 in laryngeal squamous cell carcinoma and pre-malignant laryngeal lesions

Conclusions: The present study indicates that miR-21 is involved in progression from normal to pre-malignant laryngeal lesions (PLLs) and from PLLs to laryngeal squamous cell carcinoma (LSCC). Furthermore, normalized PCR results for miR-21 might be used to discriminate between normal and ordinary hyperplasia before the emergence of dysplasias and pre-malignant lesions with malignant potential. Objective: To investigate a sensitive marker that contributes to progression from normal tissue to PLLs and from PLLs to LSCC. Methods: In 116 PLLs and LSCC patients and 19 without dysplasia matched sets of tissue and plasma samples from Beijing Tongren Hospital, miR-21 was analysed by droplet digital PCR and quantitative real-time polymerase chain reaction based on paraffin-embedded tumour tissue and plasma. Results: Compared with controls, miR-21 levels in tissue and plasma were significantly higher for both PLL and LSCC groups (for both groups vs controls: p p?相似文献   

高危型HPV阳性宫颈癌患者miRNA-34a-5p的表达及临床意义

目的　探讨高危型人乳头状瘤病毒（high risk-human papilloma virus, HR-HPV）阳性宫颈癌患者组织及血清中微小RNA（microRNA, miRNA）-34a-5p的表达及其对宫颈癌的诊断价值。方法　将100例HR-HPV阳性宫颈癌患者（宫颈癌组）、70例宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）患者（CIN组）、70例HR-HPV阳性子宫良性病变或者HPV单纯阳性的健康体检者（对照组）作为研究对象。采集上述研究对象的血清标本及70例行手术治疗的宫颈癌组患者癌组织及癌旁组织。使用实时荧光定量PCR技术测定组织及血清中miRNA-34a-5p水平，并分析miRNA-34a-5p与宫颈癌临床、病理指标的关联及血清miRNA-34a-5p对宫颈癌的诊断价值。结果　①对照组血清中miRNA-34a-5p的相对表达量高于CIN组和宫颈癌组：（0.933±0.097）vs.（0.554±0.099）vs.（0.369±0.099），差异有统计学意义（F=741.401，P=0.000）；宫颈癌组患者术前血清中miRNA-34a-5p相对表达量低于术后1周，差异有统计学意义（t=8.305，P=0.000）。有无淋巴结转移和有无远处转移的宫颈癌患者血清中miRNA-34a-5p相对表达量的差异有统计学意义（P均＜0.05）。②宫颈癌组患者癌旁组织中miRNA-34a-5p的相对表达量高于癌组织，差异具有统计学意义（t=40.313，P=0.000）。③宫颈癌组患者癌组织中的miRNA-34a-5p表达水平与血清中的表达水平呈正相关（r=0.908，P=0.000）。④以0.508为miRNA-34a-5p相对表达量的最佳临界值诊断宫颈癌，其灵敏度为83.6%，特异度为79.4%，AUC为0.860，95%置信区间为0.803～0.917。结论　HR-HPV阳性宫颈癌患者癌组织和血清中miRNA-34a-5p表达下调，对宫颈癌诊断及预后监测具有一定的参考价值。     

miRNA-34c在鼻咽癌组织中的表达及意义

目的检测miRNA-34c在鼻咽癌组织中的表达情况,并探讨其在鼻咽癌发生、发展中的意义。方法以实时定量聚合酶链式反应(quantitative real-time polymerase chain reaction,qRT-PCR)方法检测28例鼻咽癌石蜡包埋组织中相对于28例鼻咽部慢性炎症石蜡包埋组织中miRNA-34c的差异表达情况,并结合临床资料及随访结果分析miRNA-34c与鼻咽癌病例临床因素的相关性。结果鼻咽癌组织中miRNA-34c的相对表达量明显低于鼻咽部慢性炎症组织,差异有统计学意义(P<0.05)。且随着临床分期的增高、淋巴结转移,miRNA-34c的表达呈下降趋势。结论 miRNA-34c可能参与鼻咽癌的发生与发展,调控miRNA-34c的表达量有望为鼻咽癌的治疗提供一种新的思路或方法。     

肝硬化患者血清miR-122的表达及与Child-Pugh分级的关系

目的探讨肝硬化患者血清MicroRNA(miR)-122的表达水平与肝硬化Child-Pugh分级及并发症的关系。方法肝硬化患者87例,采用PCR实时荧光定量法测定患者血清miR-122水平,根据Child-Pugh分级对肝硬化患者进行分级,分析血清miR-122与肝硬化分级的关系。结果并发肝硬化腹水、消化道出血、自发性细菌性腹膜炎及失代偿期患者血清miR-122表达水平均高于未发生患者(P<0.05);不同肝硬化Child-Pugh分级血清中miR-122水平有统计学差异(P<0.05),A级与B级肝硬化患者血清miR-122水平无显著差异(P>0.05),A级和B级患者水平均显著低于C级(P<0.05)。多变量线性相关性显示,血清miR-122与丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰转移酶(GGT)、碱性磷酸酶(ALP)呈正相关(P<0.05);与国际标准化比值(INR)及肌酐(Cr)水平呈负相关(P<0.05)。结论血清miR-122水平上升提示肝硬化已经失代偿,并与腹水、消化道出血、肝肾衰竭有关。因此,血清miR-122可作为评价肝硬化患者肝脏功能及预后的潜在生物学指标。