Systemic immune inflammation index in patients with recurrent aphthous stomatitis

ObjectivesRecurrent Aphthous Stomatitis (RAS) a chronic idiopathic oral mucosal disease. But yet the etiology and pathogenesis of RAS are not exactly known, it is thought that inflammation play an important role in the pathogenesis. The aim of this study is to demonstrate the role of systemic inflammation among the possible etiological factors of RAS and to find the possible diagnostic correlation between Systemic Immune Inflammation Index (SII).MethodsPatients who were consulted the otolaryngology outpatient clinic and diagnosed with RAS between 2019–2021 were retrospectively analyzed. Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and SII values were calculated based on the results of complete blood count. Demographic and hematological parameters between control and RAS groups were compared. The statistical significance level was considered as <0.05.ResultsThere was no statistically significant difference between the control and RAS groups in terms of sex and age distributions (p = 0.566 and p = 0.173, respectively). SII, NLR and PLR values were significantly higher in the RAS group compared to the controls (p < 0.001, p < 0.001 and p = 0.001, respectively). A very strong correlation between SII and NLR, moderately strong correlation between SII and PLR and moderate correlation between NLR and PLR values were detected (respectively ρ: 0.813, 0.719, 0.532; p-values <0.001).ConclusionSII, NLR and PLR has significantly higher levels in the RAS group compared to the control group, that it supports the role of systemic inflammation in the etiopathogenesis of RAS. In addition, the results show that SII is a valuable marker for inflammation.Level of evidence4.     

免疫抑制儿童感染新型冠状病毒Omicron变异株病毒清除时间的回顾性队列研究

背景：儿童新型冠状（新冠）病毒Omicron变异株流行期间，免疫抑制状态儿童新冠病毒清除时间定量分析研究较少。 目的：探讨新冠病毒Omicron株感染后免疫抑制和非免疫抑制儿童病毒清除的时间差别，为公共卫生政策制定和精准疫情防控措施提供临床数据。 设计：回顾性队列研究。 方法：以新冠病毒Omicron变异株感染住院患儿为队列人群，分为免疫抑制组和非免疫抑制组，免疫抑制分为绝对免疫抑制、相对免疫抑制和实施免疫抑制疗法，以免疫抑制组病例的性别、年龄和新冠病毒感染的分型与非免疫抑制组行1∶3匹配。以鼻咽拭子新冠病毒PCR检测拷贝数阈（Ct）值≥35为队列终点。 主要结局指标：新冠病毒清除时间。 结果：2022年4月12日至2022年5月12日在上海市新冠病毒感染定点收治医院符合本文共同纳入和排除标准的连续病例728例。免疫抑制组33例，其中绝对免疫抑制8例，相对免疫抑制23例，接受免疫抑制疗法2例（不包括绝对和相对免疫抑制患儿）。非免疫抑制组匹配后99例。2组临床症状、新冠病毒感染治疗和疫苗接种次数差异均无统计学意义。免疫抑制组和非免疫抑制组新冠病毒清除时间分别为（16.5±6.8）和（10.3±4.4）d，差异有统计学意义。免疫抑制组和非免疫抑制组新冠病毒感染轻型病例病毒清除时间分别为（14.0 ± 8.3）和（9.7 ± 3.1）d，普通型病例病毒清除时间分别为（18.3 ± 4.9）和（11.2 ± 5.9）d，差异均有统计学意义。2组单日病毒清除率在第9~14天时差异有统计学意义（P为0.005~0.039）。2组普通型病例单日病毒清除率在第10~15天时差异有统计学意义。免疫抑制组新冠病毒感染2周后核酸检测再次呈阳性3例（9%），临床分型均较前轻，3例均未接种新冠疫苗。 结论：Omicron株感染的免疫抑制患儿病毒清除时间较非免疫抑制患儿显著延长，主要反映在第9~14天，免疫抑制患儿病毒复阳风险高，提示需要更长的隔离时间和转阴后严格的病毒监测。     

Evaluation of prime and prime-boost immunization strategies in BALB/c mice inoculated with Leishmania infantum transfected with toxic plasmids

The etiologic agents of visceral leishmaniasis are Leishmania infantum and Leishmania donovani. Despite the variety of drugs available to treat leishmaniasis, most lead to serious adverse effects, and resistance to these drugs has been reported. Currently, no leishmaniasis vaccine is available for humans. That is why the group developed transgenic L. infantum promastigote lines, which express toxic proteins after differentiation into amastigotes. That is why group developed the pFL-AMA plasmid and transfected it into L. Infantum promastigotes. This plasmid was expressed only in the amastigote form of the parasite. Sequences encoding toxic proteins (active bovine trypsin and egg avidin) were inserted in this plasmid, and the transfected parasites died after the differentiation process. In this study, two immunization protocols were performed in BALB/c mice: prime and prime-boost immunization prior to challenge with the wild-type L. infantum (WT). The parasite burdens in the spleen, liver, and bone marrow were evaluated to verify immunological protection. Histopathological analysis of the spleen and liver and the humoral immune response were also performed. The data showed that the parasite burden was reduced in prime-boosted mice in the spleen, liver, and bone marrow, indicating that mice immunized with two doses of the transfected parasites were satisfactorily protected. High levels of IgG, IgG1, and IgG2a antibodies were observed, as well as the presence of anti-inflammatory cytokine Interleukine-10 and pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN – γ) suggesting a Th1/Th2 mix response, in addition to the presence of multinucleated giant cells in the spleen and lymphocyte infiltration in the liver. Therefore, L. infantum transfected with a toxic plasmid is an excellent vaccine candidate against visceral leishmaniasis and the application of a boost before the challenge promotes greater protection against WT L. infantum infection.     

Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.     

糖尿病视网膜病变中视网膜内皮细胞功能障碍的研究进展北大核心

视网膜内皮细胞(REC)是参与糖尿病视网膜病变和许多眼部疾病的主要细胞类型之一。视网膜微血管系统有助于血-视网膜屏障的维持,这对正常的视功能至关重要。REC的改变在视网膜疾病的发生发展中起着关键作用。高血糖是糖尿病微血管损伤的重要原因,通过不同的机制导致REC功能障碍,包括向衰老表型改变、迁移和增殖能力增强、炎性凋亡等,最终导致无细胞毛细血管及病理性新生血管形成。本文对糖尿病视网膜病变中REC的功能障碍作一综述。     

宫颈癌免疫治疗的耐药机制及应对措施

宫颈癌严重威胁全球女性的生命健康，晚期宫颈癌治疗手段有限，5年生存率不到20%，是妇科肿瘤的巨大挑战。免疫治疗是晚期宫颈癌患者的重要治疗手段之一，包括免疫检查点抑制剂、治疗性疫苗和过继性T细胞免疫疗法等，但免疫治疗耐药性使部分患者无应答而效果不佳。因此，迫切需要深入研究和探讨免疫耐药的机制从而改善耐药，现归纳总结了近年有关宫颈癌中免疫耐药机制的相关研究，主要分为肿瘤内在因素和外在免疫环境改变等因素，并介绍针对免疫耐药提出的应对措施及进展。     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

The impact of preoperative immune checkpoint inhibitors on kidney and bladder cancer surgeries: a systematic review☆

Therapies based on the use of immune checkpoint inhibitors (ICIs), such as nivolumab, pembrolizumab, ipilimumab, atezolizumab, avelumab, and durvalumab, have proven effective in the treatment of metastatic urological neoplasms. Recently, it has been hypothesized that the use of this type of treatment prior to surgery could lead to an increased difficulty in renal and bladder surgeries. The literature concerning this topic, however, is still scarce and non-consensual. In our systematic review, we used the PRISMA guidelines methodology to search the pertinent literature available up to June 18, 2020 in PubMed. Additionally, we searched the related grey literature in the abstracts of the meetings of the American Society of Clinical Oncology (ASCO), American Society of Clinical Oncology Genitourinary (ASCO-GU), European Society of Medical Oncology (ESMO), and American Urological Association (AUA) from 2015 to 2020. We were able to find only 16 publications that addressed the use of ICIs prior to surgery in kidney and bladder neoplasms. The results were conflicting, and usually the issue of surgical difficulties after the use of ICIs was not directly approached. We hope that our publication may raise the awareness towards the need to further investigate the effects of neoadjuvant ICIs on surgical outcomes in urologic cancers.