Liver Transplantation for Wilson's Disease in Non-adult Patients: A Systematic Review

Introduction

Wilson's disease (WD) is a rare autosomal recessive disorder transmitted through a gene located on chromosome 13. Liver transplantation (LT) provides a therapeutic option for patients with WD presenting fulminant liver failure or drug resistance. LT in patients with WD has a twofold aim: to save the patient's life when the disorder has progressed to hepatic (or other organ) failure and to cure the underlying metabolic defect. The aim of our study was to investigate the indications, aspects and post-operative outcomes in pediatric patients (<?18 years old) with WD who underwent LT.

Trichophyton tonsurans‐induced kerion celsi with decreased defensin expression and paradoxically increased interleukin‐17A production

We report a case of kerion celsi due to Trichophyton tonsurans. An 18‐year‐old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human β‐defensin 2 (HBD‐2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)‐17A generally induces HBD‐2 production by epidermal keratinocytes, we also immunohistochemically investigated IL‐17A expression. Unexpectedly, many IL‐17A‐bearing cells were found around destructed hair follicles, indicating that IL‐17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL‐17A‐upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL‐17A may cause tissue damage and resultant scar.     

针灸联合西药对中重度间歇性过敏性鼻炎患者T淋巴细胞亚群、IL-4、IL-10、VACM-1水平的影响

目的观察针灸联合西药对中重度间歇性过敏性鼻炎患者血清T淋巴细胞亚群、炎性因子及血管细胞黏附分子-1(VACM-1)的影响。方法将120例中重度间歇性过敏性鼻炎患者随机分为对照组和治疗组,每组60例。对照组予丙酸氟替卡松鼻喷雾剂、盐酸氮卓斯汀片治疗,治疗组在对照组治疗措施的基础上加用针灸疗法。两组疗程均为28天,观察临床疗效,比较中医证候积分、血清T淋巴细胞亚群、炎性因子[白介素-4(IL-4)、白介素-10(IL-10)]及VACM-1水平的变化情况。结果①治疗组、对照组总有效率分别为95.0%、81.7%,治疗组临床疗效优于对照组(P0.05)。②治疗前与疗程结束后7天组内比较,两组中医证候(鼻塞不通、鼻痒难耐、鼻流清涕、喷嚏频作)较治疗前改善(P0.05);组间疗程结束后7天比较,治疗组中医证候改善情况优于对照组(P0.05)。③治疗前与疗程结束后7天组内比较,两组血清CD3~+、CD4~+水平和CD4~+/CD8~+较治疗前升高(P0.05),血清CD8~+、IL-4、IL-10、VCAM-1水平较治疗前降低(P0.05);组间疗程结束后7天比较,上述指标差异有统计学意义(P0.05)。结论针灸联合西医治疗中重度间歇性过敏性鼻炎疗效满意,可有效缓解患者的临床症状,改善机体免疫状态,减轻炎症反应。     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

The co-expression characteristics of LAG3 and PD-1 on the T cells of patients with breast cancer reveal a new therapeutic strategy

Many studies have shown a special interaction between LAG3 and PD-1 in T cell inhibition, while the co-expression and effect of LAG3 and PD-1 on T cells in breast cancer patients are still not very clear. Here, with strict exclusion criteria, 88 patients with breast cancer and 18 healthy controls were enrolled. The percentages of LAG3⁺PD-1⁺ T cells in their peripheral blood (PBL) and tumor infiltrating T cells (TIL) were analyzed by flow cytometry, which showed an increase in TILs but no difference in PBLs and presented differences in TILs in different molecular subtypes (P < 0.05). In triple-negative breast cancer (TNBC), the highest percentages were observed, while in ER+/PR+ breast cancer, the lowest percentages were observed; however, these percentages were not different in different clinical stages (P > 0.05). Immunohistochemical staining showed that the expression of their ligands, PD-L1, MHC class II molecular and FGL1, was inconsistent in different molecular subtypes and clinical stages. Analysis of the functions of T cells with different phenotypes showed that the proliferation and secretion capacity of LAG3⁺PD-1⁺ T cells was obviously exhausted, with more than a two-fold of decrease compared with the groups of single positive LAG3 or PD-1 (P < 0.05). Finally, in a mouse model of TNBC, the dual blockade of LAG3 and PD-1 was indicated to achieve a better anti-tumour effect than either one alone (P < 0.05), which may provide a new strategy for the immunoregulatory treatment of patients with TNBC in the future.     

Early production of IL-17A by γδ T cells in the trachea promotes viral clearance during influenza infection in mice

The innate immune response generated against influenza infection is critical for the inhibition of viral dissemination. The trachea contains different types of innate immune cells that protect the respiratory tract from pathogen invasion. Among them, γδ T cells have the ability to rapidly generate large amounts of pro-inflammatory cytokines to preserve mucosal barrier homeostasis during infection. However, little is known about their role during the early phase of influenza infection in the airways. In this study, we found that, early after infection, γδ T cells are recruited and activated in the trachea and outnumber αβ T cells during the course of the influenza infection that follows. We also showed that the majority of the recruited γδ T cells express the Vγ4 TCR chain and infiltrate in a process that involves the chemokine receptor CXCR3. In addition, we demonstrated that γδ T cells promote the recruitment of protective neutrophils and NK cells to the tracheal mucosa. Altogether, our results highlight the importance of the immune responses mediated by γδ T cells.     

托珠单抗在新型冠状病毒肺炎的应用研究探讨

2019年12月以来,新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)在武汉暴发并蔓延至全国,给整个社会带来巨大的挑战。部分COVID-19感染者早期发病并不十分凶险,但后期会突然加速进展,病人很快进入多脏器功能衰竭的状态,李兰娟院士等提出了"细胞因子风暴"概念。但目前并没有特效药物,认为IL-6是诱发细胞因子风暴的重要通路,本文结合相关文献的复习和分析,旨在综述IL-6受体阻断剂托珠单抗在新型冠状病毒肺炎危重患者使用的可行性。