极度肥胖合并阻塞性睡眠呼吸暂停患者减重代谢手术围术期管理流程

在拟行减重代谢手术（MBS）的肥胖患者尤其是极度肥胖患者（体质量指数≥50 kg/m²）中,阻塞性睡眠呼吸暂停（OSA）最常见、最危重的合并症之一,在减重人群中发病率高达35.0%~93.6%。MBS是唯一能够长期有效治疗极度肥胖同时缓解OSA病情的治疗手段,但OSA也会显著增加MBS围术期呼吸、心血管系统并发症发生率和病死率。为降低MBS围术期风险,针对OSA的围术期管理关键措施在于应在多学科诊治（MDT）基础上及时准确诊断和评估OSA,将OSA的诊疗和监测融入MBS围术期管理流程,规范个性化的精准治疗。本文结合相关文献和笔者单位临床经验,从术前、术中和术后管理三个方面介绍极度肥胖合并OSA的围术期管理流程,为精准评估最有效、安全的治疗方案提供线索和意见。     

Prostaglandin E Receptor Subtypes EP2 and EP4 Promote TH1 Cell Differentiation and TH17 Cell Expansion Through Different Signaling Modules

It is well known that prostaglandin (PG) E₂ exerts T cell suppression in vitro through elevating cAMP by its receptors, EP2 and EP4. However, such an action is rarely detected in vivo, leaving PGE₂-mediated immunosuppression an enigma. Here we show that under strong TCR stimulation, PGE₂ facilitates T helper-1 (T_H-1) differentiation through activation of phosphatidylinositol-3-kinase (PI3K) by EP2 and EP4. The PGE₂-EP4 signaling is also required for IL-23 production by activated dendritic cells (DCs), and the PGE2-EP2/EP4 signaling amplifies IL-23-mediated T_H-17 cell expansion. Administration of an EP4-selective antagonist in vivo to mice subjected to experimental allergic encephalomyelitis (EAE) decreases accumulation of both T_H-1 and T_H-17 cells in regional lymph nodes, and suppresses the disease progression. These results suggest PGE₂ promotes immune inflammation through T_H-1 differentiation and T_H-17 expansion and the EP4 antagonism is therapeutically useful for various immune diseases.

     

Dual roles of PGE2-EP4 signaling in mouse experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Although prostaglandin (PG) concentrations are increased in cerebrospinal fluid of MS patients, the role of PGs in MS is unknown. We examined this issue by subjecting mice deficient in each PG receptor type or subtype to EAE induction and using agonists or antagonists selective for each of the four PGE receptor (EP) subtypes. Among PG receptor-deficient mice, only EP4^−/− mice manifested significant suppression of EAE, which was mimicked in wild-type mice and to a greater extent, in EP2^−/− mice by administration of the EP4 antagonist ONO-AE3-208 during the immunization phase. EP4 antagonism during immunization also suppressed the generation of antigen-specific T helper (Th) 1 and Th17 cells in wild-type mice and to a greater extent, in EP2^−/− mice. ONO-AE3-208 administration at EAE onset had little effect on disease severity, and its administration throughout the experimental period did not cause significant reduction of the peak of disease, suggesting that, in addition to its facilitative action during the immunization phase, EP4 exerts a preventive action in the elicitation phase. Administration of the EP4 agonist ONO-AE1-329 at EAE onset delayed and suppressed disease progression as well as inhibited the associated increase in permeability of the blood–brain barrier. Thus, PGE₂ exerts dual functions in EAE, facilitating Th1 and Th17 cell generation redundantly through EP4 and EP2 during immunization and attenuating invasion of these cells into the brain by protecting the blood–brain barrier through EP4.     

Prostaglandin E2 directly inhibits the conversion of inducible regulatory T cells through EP2 and EP4 receptors via antagonizing TGF‐β signalling

Regulatory T (Treg) cells are essential for control of inflammatory processes by suppressing effector T‐cell functions. The actions of PGE₂ on the development and function of Treg cells, particularly under inflammatory conditions, are debated. In this study, we employed pharmacological and genetic approaches to examine whether PGE₂ had a direct action on T cells to modulate de novo differentiation of Treg cells. We found that TGF‐β‐induced Foxp3 expression and iTreg cell differentiation in vitro is markedly inhibited by PGE₂, which was mediated by the receptors EP2 and EP4. Mechanistically, PGE₂‐EP2/EP4 signalling interrupts TGF‐β signalling during iTreg differentiation. Moreover, EP4 deficiency in T cells impaired iTreg cell differentiation in vivo. Thus, our results demonstrate that PGE₂ negatively regulates iTreg cell differentiation through a direct action on T cells, highlighting the potential for selectively targeting the PGE₂‐EP2/EP4 pathway to control T cell‐mediated inflammation.     

Prognostic Predictors of Endodontic Microsurgery: Radiographic Assessment

ObjectiveThis study aimed to compare the healing outcomes of endodontic microsurgery (EMS) using 2-dimensional (2D) and 3-dimensional (3D) radiographic evaluation in a Chinese population. The prognostic factors of EMS were identified according to the 2D and 3D healing classifications.Materials and methodsThe teeth (n = 82) were studied using 2D and 3D radiographic examinations. The 2D and 3D healing criteria were used to evaluate the healing outcome. Prognostic factors were investigated based on healing outcomes. Data were analysed using SPSS, and P < .05 was considered significant.ResultsThere were significant differences between 2D and 3D healing outcomes (P = .004). For the 3D images, age older than 45 years was found to be a significant negative predictor (P = .005).ConclusionsCone-beam computed tomographic images provided more precise evaluation of periapical lesions and healing outcomes of EMS than conventional periapical radiographs. Age (>45 years) of the patients exhibited a significant influence on the healing outcome of EMS as determined using 3D images.     

自拟强心汤治疗慢性心力衰竭40例疗效观察

自2001年以来用自拟强心汤辨证治疗慢性心衰,对临床症状、体征及心功能改善均取得一定效果,现总结报告如下。1临床资料共观察40例,其中男18例,女22例;年龄最小11岁,最大76岁,平均43.5岁;病程最短3月,最长28a;确诊风湿性心脏病8例,冠心病14例,高心病12例,慢性肺心病3例,心肌病1例,心肌炎2例。以左心衰为主者24例,右心衰为主者3例,全心衰13例。临床表现以喘促、心悸、水肿、不同程度紫绀为主,部分病例伴心律失常。心电图、超声心电图、胸片均有明显异常。患者均为使用西药疗效不佳后,采用中药治疗者。所有病例符合《实用内科学》四级心功能标…     

多维显微技术测量关节液中有形颗粒的形态及其临床意义

目的探讨关节液中有形颗粒的形态大小与膝关节疾病的相关关系。方法抽取正常人和KOA患者的关节液,利用多维显微技术观察、记录、测量不同疾病关节液中有形颗粒的大小参数(接触面积、周长、长轴、短轴、单位面积上的颗粒数)和形态(形状归化因子、伸长率、紧密度、单位面积积分光密度)参数,并分析它们与关节疾病类型的关系。结果①KOA和KTS关节液中有形颗粒的接触面积、周长、长轴和短轴均显著大于正常关节液(p<0.001),单位面积上的颗粒数显著小于正常关节液(p<0.001)。②KOA和KTS关节液中有形颗粒的伸长率显著大于正常关节液(p<0.001),形状归化因子、紧密度和单位面积上的积分光密度均显著小于正常关节液(p<0.001)。结论关节液中有形颗粒的形态、大小等参数与关节疾病的类型密切相关,可为关节疾病的早期诊断与治疗提供可靠的参考。     

Prostaglandin E2, an Immunoactivator

Diseases caused by immune inflammation, such as rheumatoid arthritis, multiple sclerosis, and Crohn’s disease, are intractable diseases to which novel therapeutics are highly demanded. Prostaglandin (PG) E₂ is the most ubiquitously produced PG with various actions. PGE₂ has been traditionally regarded as an immunosuppressant based on its inhibition of T cell activation in vitro. However, in vivo relevance of the immunosuppressant action of PGE₂ has remained obscure. Recently, several groups including ourselves have made unexpected findings that PGE₂ facilitates expansion of the Th17 subset of T helper cells of both human and mouse through elevation of cAMP via PGE receptors EP2 and EP4. We have further found that PGE₂ can induce and not suppress Th1 differentiation under certain conditions, again, through EP2 and EP4. Given the putative roles of these Th subsets in immune diseases such as the above, these findings suggest that, on the contrary to the traditional view, PGE₂ functions as a mediator of immune inflammation. Consistently, administration of an EP4 antagonist could suppress disease progression and development of antigen-specific Th17 cells in mice subjected to experimental allergic encephalomyelitis and contact hypersensitivity. In this perspective, we review these findings and discuss the prospect of EP4 antagonists as immunomodulatory drugs.