滋肾育胎丸加减方预防ACA阳性者不良妊娠结局的效果及机制研究＊

目的 探讨滋肾育胎丸加减方预防抗磷脂抗体（ACA）阳性者不良妊娠结局的效果及机制研究。方法 选取2016年2月至2019年2月我院收治的89例ACA阳性，先兆性流产或有习惯性流产（RSA）史患者，将采用西医治疗的40例作为对照组，将采用西医联合滋肾育胎丸加减方治疗的49例作为观察组，比较两组中医证候疗效、中医证候积分、ACA-IgA、ACA-IgM、ACA-IgG、凝血指标［血小板聚集功能（PAF）、活化蛋白C（PC）、抗凝血酶（AT）、纤溶酶原激活抑制物-1（PAI-1）］、Th1/Th2细胞因子［干扰素γ（IFN-γ）、白介素-2（IL-2）、白介素-4（IL-4）、白介素-10（IL-10）］、妊娠结局、安全性。结果 治疗2周后检测ACA，观察组2例未降低，对照组11例未降低，观察组未降低患者占比低于对照组（P<0.05）；观察组总有效率100.00%高于对照组85.00%（P<0.05）；观察组治疗4周、7周后中医证候积分低于对照组（P<0.05）；观察组治疗4周、7周后ACA-IgA、ACA-IgM、ACA-IgG低于对照组（P<0.05）；观察组治疗4周、7周后PAF、PAI-1低于对照组，PC、AT高于对照组（P<0.05）；观察组治疗4周、7周后IFN-γ、IL-2低于对照组，IL-4、IL-10高于对照组（P<0.05）；观察组活产率95.92%高于对照组80.00%（P<0.05）；组间不良反应总发生率比较，差异无统计学意义（P>0.05）。结论 动态监测ACA对滋肾育胎丸加减方精准应用具有指导意义，指导滋肾育胎丸加减方通过调理脏腑、气血、经络功能，改善先兆性流产或有RSA史患者临床症状及凝血因子指标，降低ACA水平，并可改善患者免疫耐受功能，提高胎儿活产率，且安全性高。     

Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

Interleukin 1 alpha (IL1A) polymorphisms and risk of endometriosis in Iranian population: a case-control study

Abstract

Endometriosis is one of the most common gynecological diseases and a major cause of pain and infertility. It is influenced by genetic, epigenetic, and environmental factors. Recently, genome-wide association studies have revealed a strong association between IL1A single nucleotide polymorphisms (SNPs) and increased risk of endometriosis in Japanese women. The aim of the present study was to evaluate the association of three IL1A SNPs, rs17561, rs1304037, and rs2856836 with the risk of endometriosis in Iranian population. Totally, 105 women with diagnosis of endometriosis and 102 healthy women as control group were included. Three SNPs of the IL1A, rs17561?G/T, rs1304037 A/G, and rs2856836 T/C, were genotyped by PCR and RFLP. The rs2856836?TC genotype was significantly higher (p?=?.002; OR?=?3.1, 95% CI: 1.5–6.5) in the patients (28.1%) than the control group (12.7%). The rs2856836?CC genotype was significantly higher (p?=?.047; OR?=?2.3, 95% CI: 1.0–5.3) in the patients (17.5%) than the control group (10.8%). The rs2856836 C allele was significantly higher (p?=?.001; OR?=?2.2, 95% CI: 1.4–3.6) in the patients (31.6%) than the control group (17.2%). The IL1A rs2856836 T/C SNP was associated with susceptibility to endometriosis and the rs2856836 C allele may increase the risk of endometriosis in Iranian women.     

炎症性肠病患儿血清Th17相关细胞因子表达及其意义

目的　探讨儿童IBD患者血清中Th17相关细胞因子的表达水平及其临床意义。方法　收集2017年4月至2019年5月在西安交通大学附属儿童医院消化科住院治疗的儿童IBD患者40例，以同期21例非炎症性疾病儿童作为对照组。采集受检者血清标本，通过酶联免疫吸附试验检测白细胞介素-17A（IL-17A）、 IL-17F、 IL-21、 IL-22、 IL-25的表达水平。结果　IL-17A、 IL-17F、 IL-21和IL-22在溃疡性结肠炎（UC）及克罗恩病（CD）患儿血清中表达明显升高，IL-25明显降低（P＜0.05）；IL-17A、 IL-17F及IL-21血清水平与UC患儿疾病活动度呈正相关（P＜0.05）；IL-21在UC患儿血清中的表达与IL-17A和IL-17F的表达呈正相关（P＜0.05）。结论　Th17相关细胞因子在IBD患儿血清中表达失调，为进一步研究Th17细胞在儿童IBD中的作用提供了依据；IL-17A、 IL-17F、 IL-21血清水平与UC患儿疾病活动度呈正相关，表明其可能是Th17细胞触发儿童UC的重要促炎细胞因子。     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

利咽散结方对自发性高血压大鼠血压及相关炎性因子的影响

目的研究利咽散结方对自发性高血压大鼠血压及相关炎性因子的影响。方法将36只自发性高血压大鼠随机分为利咽散结方组、氨氯地平组、模型组,每组12只。正常WKY大鼠12只作为正常组。利咽散结方组给予利咽散结方药液15.6 g/kg灌胃,氨氯地平组给予氨氯地平药液0.001 g/kg灌胃,模型组和正常组均给予等体积的蒸馏水灌胃,均1次/d,连续8周。测量各组大鼠灌胃前及灌胃2周、4周、6周、8周后血压,末次灌胃结束后用ELISA法测定血清炎性因子肿瘤坏死因子(TNF-α)、超敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平。结果利咽散结方组与氨氯地平组灌胃2周、4周、6周、8周后收缩压与舒张压均显著低于同期模型组(P均<0.05);利咽散结方组灌胃2周、4周、6周、8周后收缩压均显著高于同期氨氯地平组(P<0.05),而舒张压与同期氨氯地平组比较差异均无统计学意义(P均>0.05)。模型组血清TNF-α、hs-CRP、IL-6水平均明显高于正常组(P均<0.05),IL-10水平明显低于正常组(P<0.05);利咽散结方组与氨氯地平组血清TNF-α、hs-CRP、IL-6水平均明显低于模型组(P均<0.05),且利咽散结方组均明显低于氨氯地平组(P均<0.05);利咽散结方组与氨氯地平组血清IL-10水平均明显高于模型组(P均<0.05),且利咽散结方组明显高于氨氯地平组(P<0.05)。结论利咽散结方可显著降低自发性高血压大鼠血压,其降收缩压效果不如氨氯地平,降舒张压效果与氨氯地平相近,其作用机制可能与调节炎性因子水平有关。