基于16S rDNA测序的肠道菌群探讨解郁祛痰化浊方对高脂饮食大鼠肠-肝轴的影响

目的 研究解郁祛痰化浊方（JQHP）对高脂饮食大鼠肠道菌群的影响，探讨中药调控肠道微生物群进而恢复肠-肝轴的平衡。方法 将70只雄性SPF级别Wistar大鼠随机分为正常组（10只）与模型组（60只），正常组饲喂正常饲料，模型组饲喂高脂饲料。12周后将模型组随机分为6组，每组10只，即模型组，血脂康组，立普妥组，JQHP低、中、高剂量组。JQHP低、中、高剂量组分别灌胃JQHP颗粒剂0.4，0.8，1.6 g·kg^-1，立普妥组予立普妥2 mg·kg^-1，血脂康组予血脂康0.1 g·kg^-1，正常组和模型组大鼠灌胃同等量蒸馏水，连续灌胃8周后收集粪便，进行16S rRNA基因测序，行腹主动脉取血检测血脂，取肝脏组织及回肠组织苏木素-伊红（HE）染色后进行病理形态学观察。结果 与正常组比较，模型组大鼠血脂四项总胆固醇（TC），甘油三酯（TG），低密度脂蛋白胆固醇（LDL-C）均见明显升高，高密度脂蛋白胆固醇（HDL-C）降低（P<0.01）；与模型组比较，血脂康组、立普妥组TC，TG显著性下降（P<0.01），血脂康组HDL-C升高（P<0.05）。JQHP中剂量组较模型组对肝脏脂肪样变有一定的缓解作用，可以减轻炎性细胞的浸润情况。JQHP可使回肠结构淋巴组织增生情况好转，且中剂量组疗效最显著。Shannon曲线结果表明，与正常组比较，JQHP中剂量组显著提高（P<0.01）；与模型组比较，JQHP中、高剂量组明显升高（P<0.05，P<0.01）；与JQHP中剂量组比较，其他用药组降低（P<0.05，P<0.01）。主成分多样性分析（PCA）示中药中剂量组多样性和丰度高于其他用药组。线性判别分析（LDA）中，与正常组比较，模型组拟杆菌纲，瘤胃球菌科，拟杆菌S24-7，瘤胃球菌UCG-005下调（P<0.01），脱硫弧菌目、丹毒丝菌目、毛螺菌科上调（P<0.05，P<0.01）。与模型组比较，JQHP中剂量组的拟杆菌纲，瘤胃球菌科，拟杆菌S24-7，瘤胃球菌UCG-005上调（P<0.05，P<0.01），丹毒丝菌目下调（P<0.01）。与JQHP中剂量组比较，其他用药组拟杆菌纲，瘤胃球菌科，拟杆菌S24-7，瘤胃球菌UCG-005中降低（P<0.05，P<0.01），在丹毒丝菌目、毛螺菌科中升高（P<0.05，P<0.01）。结论 JQHP调整肠道物种丰度和多样性，改善肝脏组织和回肠黏膜状态，调节血脂水平，恢复正常肠道生态环境，可能与调节与炎症相关的肠道菌群而恢复肠-肝轴平衡有关，以中剂量组效果最佳。     

MiR-92b-3p ameliorates inflammation and autophagy by targeting TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells

Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality. Dysregulation of microRNAs (miRNAs) was involved in human diseases, including AP. However, the effects of miR-92b-3p on AP process and its mechanism remain not been fully clarified. The expression levels of miR-92b-3p and tumor necrosis factor receptor-associated factor-3 (TRAF3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of TRAF3, tumor necrosis factor α (TNF-α) TNF-α, interleukin-6 (IL-6), phosphorylated mitogen-activated protein kinase kinase 3 (p-MKK3), MKK3, p38 and phosphorylated p38 (p-p38) were detected by western blot. The concentration of TNF-α and IL-6 in the medium was measured using ELISA kits. The possible binding sites of miR-92b-3p and TRAF3 were predicted by TargetScan and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression level of miR-92b-3p was decreased and TRAF3 expression was increased in AR42J cells stimulated with caerulein. Moreover, the protein levels of pro-inflammatory cytokines (TNF-α and IL-6) were markedly elevated, and the expression levels of autophagy-related markers Beclin1 as well as the ratio of LC3-II/I were obviously increased in AR42J cells treated with caerulein. In addition, overexpression of miR-92b-3p or knockdown of TRAF3 significantly suppressed the release of pro-inflammatory cytokines and autophagy in caerulein-induced AR42J cells. Furthermore, TRAF3 was a direct target of miR-92b-3p and its upregulation reversed the effects of miR-92b-3p overexpression on inflammatory response and autophagy. Besides, overexpression of miR-92b-3p inhibited the activation of the MKK3-p38 pathway by affecting TRAF3 expression. In conclusion, miR-92b-3p attenuated inflammatory response and autophagy by downregulating TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells, providing a novel avenue for treatment of AP.     

Lomitapide for the treatment of hypertriglyceridemia

Introduction: Severe genetic forms of hypertriglyceridemia carry a risk of life-threatening pancreatitis and lack available effective treatments. Lomitapide is a microsomal triglyceride transfer protein inhibitor currently approved for treatment of homozygous familial hypercholesterolemia that may be useful in the management of severe hypertriglyceridemia.

Areas covered: Published trials of lomitapide that reported plasma triglyceride response were reviewed, as was a case report of a patient with hypertriglyceridemia who was treated for 13 years with lomitapide. ClinicalTrials.gov was also reviewed for any unpublished results and ongoing trials.

Expert opinion: Lomitapide demonstrates effective triglyceride lowering and may be a useful treatment for patients with genetic hypertriglyceridemia and recurrent acute pancreatitis who are refractory to traditional treatment. However, long term hepatic safety may be a concern and direct clinical trial-level data are lacking for this indication.     

Primary hyperparathyroidism presenting as severe hypercalcemia with acute pancreatitis in pregnancy

Abstract

Primary hyperparathyroidism presenting first time with severe hypercalcemia is rare in pregnancy. We report a case of primary hyperparathyroidism due to a cystic parathyroid adenoma presenting as severe hypercalcemia with acute pancreatitis in second trimester of pregnancy. Acute pancreatitis was managed by conservative treatment. Hypercalcemia failed to respond to medical management and ultimately responded to ultrasound-guided ethanol ablation of parathyroid adenoma. The delivery was uneventful and patient continues to remain normocalcemic during follow up. As such, ethanol ablation of parathyroid adenoma may be considered during pregnancy in case of failure of response to medical management and when surgical removal of parathyroid adenoma is not safe.     

自身免疫性胰腺炎的诊断

自身免疫性胰腺炎（AIP）是一类特殊的慢性胰腺炎，其临床上依据组织学分为Ⅰ型和Ⅱ型。我国以Ⅰ型为主，是 IgG4相关性疾病的一部分，常表现为梗阻性黄疸或胰腺实质的肿块。组织学上表现为病变组织大量淋巴浆细胞的浸润及慢性纤维化。虽然国际胰腺病协会围绕其影像学、血清学、组织学及激素治疗的反应制定了诊断标准，但 AIP的临床表现较为隐匿和多样，其诊断仍然具有挑战性，特别是表现为胰腺肿块的患者，需要时刻警惕胰腺癌的风险。本文从影像学、组织学角度对文献进行了概述，重点是这种复杂疾病的诊断及误诊的风险，以期提高本病的鉴别诊断水平。     

张仲景阳明腑实腹痛诊治理论对急性胰腺炎治疗的指导意义

张仲景对阳明腑实腹痛的诊治是系统的、有层次性的,按照腹痛的不同部位、不同性质及其不同的本证及兼证、变证,在通腑导滞的基础上治疗方药各有化裁。梳理阳明腑实腹痛诊治的层次性,讨论腹痛诊治理论的层次性对急性胰腺炎不同阶段、不同表现诊疗的指导意义,并提出"通腑导滞、中病即止"在重症急性胰腺炎治疗中的新观念,即通腑导滞不应仅局限于"得快利即止",而应涵盖于重症急性胰腺炎治疗全过程。     

炎性指标联合检测诊断急性胰腺炎继发感染的价值

目的探讨降钙素原(PCT)、C-反应蛋白(CRP)、白细胞介素-6(IL-6)在急性胰腺炎(AP)继发感染诊断中的价值,减少全身炎性综合征的发生率。方法对2012年1月-2013年12月102例AP患者根据细菌培养结果分为感染组50例及非感染组52例,感染组再分为重度脓血症组18例及轻度脓血症组32例,两组均于入院第1、3、7、14天抽取血液标本,测量PCT、CRP、IL-6浓度。结果感染组第1、3天PCT阳性率为44.00%、20.00%,高于非感染组的25.00%、5.77%,差异有统计学意义(P<0.05);第3、7、14天感染组PCT与非感染组比较差异有统计学意义(P<0.05);感染组第1、3、7、14天IL-6与非感染组比较,差异有统计学意义(P<0.05);感染组第1、3、7、14天CRP与非感染组比较差异有统计学意义(P<0.05),但组内第3、7天IL-6、CRP水平与第1天比较,差异均无统计学意义,第14天水平均较第1天显著下降,差异有统计学意义(P<0.05);重度脓血症组各时段PCT、CRP、IL-6水平均高于非重症脓血症组,差异有统计学意义(P<0.05)。结论 PCT、CRP、IL-6联合检测对AP继发感染早期诊断有较高价值,其中PCT的诊断敏感度最高。