目的 探讨临床病理、病理生理学及治疗学(CPPT)教学模式在消化系统疾病教学中的应用,回顾分析某大学学生采用不同教学模式后的成绩情况,并针对CPPT模式试行过程中暴露的问题予以修正.方法 选取2015年和2019年学习消化系统疾病相关课程的某校临床医学专业的学生285人为研究对象.2015年采用传统的讲授式教学,作为对照组;2019年采用CPPT教学模式,作为实验组.课程结束后进行理论考核并发放自我评价问卷及满意度调查问卷,统计并分析两组成绩及问卷结果.结果 实验组的理论考核、病例分析及切片识读成绩均明显高于对照组,差异均有统计学意义(P<0.05).实验组学生的课堂氛围、理论知识掌握情况、学习兴趣、自主学习能力、知识运用能力、切片识读能力、临床思维能力、沟通交流能力和团队协作能力均高于对照组,差异具有统计学意义(P<0.05).实验组学生对于病例讨论、切片识读、教学流程、助教安排、复习串讲及测试试题难易度较为满意(满意度>80％),但理论课讲解、课时分配及配套教材方面有待进一步提高(满意度<80％).结论 CPPT教学改革模式优于传统模式,既考虑医学发展的需求,又关注学生能力的发展,利于培养高水平、高素质的医学人才.

Objective To observe effects of medication use on small airway function, airway inflammation and acute exacerbations in patients with clinically controlled asthma. Methods Forced expiratory flow over the middle half of the forced expiratory curve (FEF 25%–75% ), percentage of eosinophil, concentrations of eosinophil cationic protein (ECP) and interleukin (IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone. Subsequently, acute exacerbations were compared between two groups during the 24-week follow-up period. Results FEF 25%–75% in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone. Meanwhile, the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone. Additionally, the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period. Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations, presumably secondary to reduction in airway inflammation.

Coronavirus disease 2019 (COVID-19) is a newly emerged disease with various clinical manifestations and imaging features. The diagnosis of COVID-19 depends on a positive nucleic acid amplification test by real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the clinical manifestations and imaging features of COVID-19 are non-specific, and nucleic acid test for SARS-CoV-2 can have false-negative results. It is presently believed that detection of specific antibodies to SARS-CoV-2 is an effective screening and diagnostic indicator for SARS-CoV-2 infection. Thus, a combination of nucleic acid and specific antibody tests for SARS-CoV-2 will be more effective to diagnose COVID-19, especially to exclude suspected cases.

Lung interstitial macrophages (IMs) can be polarized towards an alternative activation phenotype in ovalbumin (OVA)-induced asthmatic mice. However, the role of alternative activation of lung IMs in Th2 cell responses in the asthmatic murine is still unclear. Here, we leverage an anti-F4/80 treatment which has been shown to selectively deplete IMs in mice and investigate how this treatment modulates Th2 cell responses in lung and whether the modulation is dependent on lung IMs in murine models of asthma. We show that anti-F4/80 treatment alleviates Th2 cell responses in mice immunized and challenged with OVA or house dust mite (HDM). The anti-F4/80 treatment does not target lung alveolar macrophages (AMs) in OVA-induced asthmatic mice or impact the abundance of other immune cell types, including B cells, T cells, and NK cells in wild-type mice. However, this treatment does inhibit the expression of polarized markers of alternatively activated macrophages, including arginase-1, Ym-1, and Fizz-1 in the lung tissues from OVA-induced asthmatic mice. Furthermore, we find that the inhibitory effects of anti-F4/80 treatment on Th2 cell responses can be reversed upon adoptive transfer of lung IMs. Taken together, our data show that anti-F4/80 treatment attenuates Th2 cell responses, which is at least partially related to depletion of lung IMs in murine models of asthma. This suggests that targeted lung IMs may provide a potential therapeutic protocol for the treatment of asthmatics.

目的 发现临床病理生理及治疗学(CPPT)讨论课教学效果好的师资群体及其特征,建立临床医学讨论课师资评价模式.方法 研究对象为2018年参加CPPT神经病学课程的五年制、八年制及5+3年制临床医学生184名,按小班随机分配讨论课老师一名,可为教学医院专科高级或中级职称老师,或学生助教(TA)一名,课程结束后在线填写对授课老师的评价表,结合专科期末考核成绩综合评价师资教学效果.结果 学生对于授课老师的专业能力、对课程的讲授和对学生的帮助三个方面的认可度达到90.2％、86.4％和86.4％;TA带教学生的专科考核平均分显著高于高级职称师资带教成绩,且高分段学生人数的比例高于中级职称老师高分数段学生人数的比例(P<0.05).结论 学生助教参与的CPPT讨论课教学效果好,鼓励多选拔并培养高年级学生当助教参与讨论课的讲授.

Some studies have shown that maturation of dendritic cells (DCs) is modulated directly by pathogen components via pattern recognition receptors such as Toll-like receptors, but also by signal like CD40 ligand (CD40 L or CD154) mediated by activated T cells. Several reports indicate that invariant natural killer T (iNKT) cells up-regulate CD40 L upon stimulation and thereby induce activation and maturation of DCs through crosslink with CD40. Our previous findings indicated that iNKT cells promote Th2 cell responses through the induction of immunogenic maturation of lung DCs (LDCs) in the asthmatic murine, but its mechanism remains unclear. Therefore, we investigated the immunomodulatory effects of blockade of CD40 L using anti-CD40 L treatment on Th2 cell responses and immunogenic maturation of LDCs, and further analyzed whether these influences of blockade of CD40 L were related to lung iNKT cells using iNKT cell-deficient mice and the combination treatment of specific iNKT cell activation with anti-CD40 L treatment in murine models of asthma. Our findings showed that blockade of CD40 L using anti-CD40 L treatment attenuated Th2 cell responses in wild-type (WT) mice, but not in CD1d-deficient mice sensitized and challenged with ovalbumin (OVA) or house dust mite (HDM). Meanwhile, blockade of CD40 L down-regulated immunogenic maturation of LDCs in WT mice, but not in CD1d-deficient mice sensitized and challenged with OVA. Additionally, agonistic anti-CD40 treatment reversed the inhibitory effects of anti-CD40 L treatment on Th2 cell responses and LDC activation in an OVA-induced mouse model of asthma. Furthermore, LDCs from asthmatic mice treated with anti-CD40 L could significantly reduce the influence on Th2 cell responses in vivo and in vitro. Finally, α-Galactosylceramide plus anti-CD40 L treatment stimulated lung iNKT cells, but suppressed Th2 cell responses in the asthmatic mice. Taken together, our data raise an evidence that blockade of CD40 L attenuates Th2 cell responses through the inhibition of immunogenic maturation of LDCs, which may be at least partially related to lung iNKT cells in murine models of asthma.

Changes of maximum expiratory flow at 25% and 50% of vital capacity (MEF25 and MEF50, respectively), and predominant parameters indicating small airways function in asthmatics before and after bronchodilator (BD) reversibility test have been less interpreted. Our study aimed to investigate the clinical role of changes of MEF25 and MEF50 before and after BD reversibility test in diagnosing asthma. Forced expiratory volume in the first second (FEV1), MEF25, and MEF50 were measured before and after BD reversibility test in 207 asthmatic patients using standard process. Forty healthy individuals were enrolled as controls. Receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of reversibility of MEF25 and MEF50 before and after BD reversibility test (ΔMEF25% and ΔMEF50%, respectively) in diagnosing asthma. Among these functional criteria, ΔMEF25% and ΔMEF50% ≥ 25% performed the best diagnostic performance. The sensitivity, specificity, and accuracy of ΔMEF25% ≥ 25% as an objective diagnostic test for asthma were 63.29%, 87.50%, and 67.21%, and of ΔMEF50% ≥ 25% were 79.23%, 85.00%, and 80.16%, respectively. The area under the ROC curve of the indicators was 0.8203 and 0.9104, respectively. By contrast, an increase in FEV1 ≥ 12% and 200 mL demonstrated a sensitivity of 62.32%, specificity of 82.50%, and accuracy of 65.59% in diagnosing asthma. The changes of MEF25 and MEF50 before and after BD reversibility test may be of additional value in the clinical diagnosis of asthma, with cutoff values of 25% being the most.

Asthma is a common inflammatory pulmonary disorder involving a diverse array of immune cells such as proinflammatory T helper 2 (Th2) cells. We recently reported that intraperitoneal injection of α-galactosylceramide (α-GalCer) can stimulate the lung invariant natural killer T (iNKT) cells and does not lead to airway inflammation in WT mice. Other studies indicate that iNKT cells play an important role in inducing regulatory T cells (Treg cells) and peripheral tolerance. Using iNKT cell- knockout mice, functional inactivation of Treg cells, and co-culture experiments in murine asthma models, we investigated the immunoregulatory effects of α-GalCer treatment before allergen sensitization on Th2 cell responses. We also studied whether α-GalCer's effects require lung Treg cells induced by activated iNKT cells. Our results disclosed that intraperitoneal administration of α-GalCer before allergen sensitization could promote the expansion and suppressive activity of lung CD4+FoxP3+ Treg cells. These effects were accompanied by down-regulated Th2 cell responses and decreased immunogenic maturation of lung dendritic cells in WT mice. However, these changes were absent in CD1d-/- mice immunized and challenged with ovalbumin or house dust mites, indicating that the effects of α-GalCer on Treg cells mainly require iNKT cells. Moreover, functional inactivation of Treg cells could reverse the inhibitory ability of this α-GalCer therapy on Th2 cell responses in a murine asthma model. Our findings indicate that intraperitoneal administration of α-GalCer before the development of asthma symptoms induces the generation of lung Treg cells via iNKT cells and may provide a potential therapeutic strategy to prevent allergic asthma.

Positive bronchodilation (BD) tests can be noticed in some stable chronic obstructive pulmonary disease (COPD) patients. The characteristics of airway inflammation in this entity remain unclear. Our study aimed to identify the characteristics of airway inflammation in stable COPD patients with positive BD tests. The airway inflammation was assessed in 88 patients with stable COPD using the examination of induced sputum in the aftermath of lung function and BD tests. Cellular counts and the levels of molecular markers including eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin-5 (IL-5), and IL-8 were assayed by Wright’s stain, Immuno-CAP system, and ELISA, RT-PCR. Among the 88 patients with stable COPD, 20 (22.7%) showed positive BD tests. The values of eosinophils (4.7%±3.4%) and ECP (90.1±41.6 ng/mL) in induced sputum in stable COPD patients with positive BD tests were markedly elevated as compared with those in stable COPD patients with negative BD tests or in healthy controls (all P>0.05), but significantly lower than those in asthmatic patients (all P<0.01). The IL-5 in sputum supernatant was significantly decreased in stable COPD patients with positive BD tests as compared with the patients with asthma (12.5±7.8 vs. 48.2±26.0 ng/mL;.P<0.01). However, healthy controls exhibited similar concentrations of IL-5 in induced sputum with patients with stable COPD, whether with positive or negative BD tests (all P>0.05). Moreover, the values of neutrophils (61.8%±15.1%), MPO (574.0±111.8 ng/mL), and IL-8 (32.6±13.4 ng/mL) in induced sputum in stable COPD patients with positive BD tests were significantly higher than those in asthmatics or normal controls (all P<0.01). However, the values of the above inflammatory markers in induced sputum were similar among stable COPD patients with positive or negative BD tests (all P>0.05). The stable COPD patients with positive BD tests may present not only eosinophilic airway inflammation but also neutrophilic airway inflammation.

目的 了解某大学临床医学研究生参与临床病理、病理生理及治疗(CPPT)课程后自主学习、临床思维能力的提高情况,同时针对CPPT教改课程试行所暴露问题予以修正,为合理设置CPPT课程的教学内容及形式提供客观证据.方法 对某院3个年级的临床医学专业学生随机抽取50人作为实践班,另147人作为普通班,进行考试以及师生自填式问卷调查并进行分析,调查内容主要涉及对于CPPT课程的认真情况及相关课程教学内容的满意度.结果 2012级五年制实验班内外妇儿笔试成绩平均分/及格率分别为(75.87,70.68,84.08,85.17)分/(83.45,87.50,100,100)％,均高于普通班内外妇儿笔试成绩(64.51,61.73,74.58,75.59)分/(65.18,55.36,88.39,97.32)％,差异有统计学意义(P<0.05).病例分析题和病史采集题2类题型的成绩对比,实验班成绩均明显高于普通班,差异有统计学意义(P<0.05).调查问卷结果显示,实验班学生对CPPT课程教改模式的肯定程度高于普通班学生.此外,长年制学生临床执业医师考试通过率并无明显差异(P>0.05).结论 对于临床医学生,CPPT教改模式优于传统教学模式,有助于巩固理论知识,培养临床思维能力以及良好的职业素养.

Our previous study showed that intraperitoneal injection of alpha-galactosylceramide (alpha-GalCer) has the ability to activate lung iNKT cells, but alpha-GalCer-activated iNKT cells do not result in airway inflammation in wild-type (WT) mice. Many studies showed that iNKT cells had the capacity to induce Treg cells, which gave rise to peripheral tolerance. Therefore, we examined the influence of intraperitoneal administration of alpha-GalCer on the expansion and suppressive activity of lung Treg cells using iNKT cell-knockout mice and co-culture experiments in vitro. We also compared airway inflammation and airway hyperresponsiveness (AHR) after alpha-GalCer administration in specific anti-CD25 mAb-treated mice. Our data showed that intraperitoneal injection of alpha-GalCer could promote the expansion of lung Treg cells in WT mice, but not in iNKT cell-knockout mice. However, alpha-GalCer administration could not boost suppressive activity of Treg cells in WT mice and iNKT cell-knockout mice. Interestingly, functional inactivation of Treg cells could induce airway inflammation and AHR in WT mice treated with alpha-GalCer. Furthermore, alpha-GalCer administration could enhance iNKT cells to secrete IL-2, and neutralization of IL-2 reduced the expansion of Treg cells in vivo and in vitro. Thus, intraperitoneal administration of alpha-GalCer can induce the generation of lung Treg cells in mice through the release of IL-2 by the activated iNKT cells.

通过对武汉大学医学部第五届CPPT试点班学生进行问卷调查,了解整合课程之一的临床病理病生及治疗学(Clinical Pathophisiology and Theraputics,CPPT)使用的CPPT讲义存在的问题,分析CPPT讲义的问题的主要原因,结合讲义存在的问题和学生对CPPT讲义的评价,提出相应建议.

Introduction Acute exacerbation of COPD (AECOPD) and left heart failure (LHF) commonly exist together in clinical practice. However, the identification of AECOPD concurrent with LHF is currently challenging. Our study aimed to investigate the role of plasma N-terminal brain natriuretic pro-peptide (NT-proBNP) in diagnosing elderly patients with AECOPD associated with LHF. Methods and results LHF was diagnosed in patients with AECOPD according to echocardiographic criteria, and the levels of NT-proBNP in plasma were measured by quantitative electrochemiluminescence assay. Among the 655 patients with AECOPD, 158 (24.1%) had comorbid LHF, whether systolic (n=108, 68.4%) or diastolic (n=50, 31.6%). The plasma concentrations of NT-proBNP in elderly patients with AECOPD associated with LHF were markedly elevated, compared with those with only AECOPD (4,542.5 and 763.0 ng/L, respectively, P<0.01). The receiver operating characteristic curve indicated a diagnostic cutoff value of 1,677.5 ng/L of NT-proBNP in plasma for ascertaining the presence of LHF in AECOPD, with a sensitivity of 87.9%, a specificity of 88.5%, and an accuracy of 88.4%. Conclusion The plasma level of NT-proBNP may be a useful indicator in diagnosing AECOPD associated with LHF.

目的 探讨白三烯E4在中重度稳定期慢性阻塞性肺疾病(chronic obstructive pulnonary disease,COPD)发病机制中的作用,及白三烯受体拮抗剂治疗的临床疗效.方法 将60例中重度稳定期COPD患者随机分为孟鲁司特组及常规治疗组各30例,取30例健康患者为对照组.观察3个月治疗前后各组尿白三烯E4(uLTE4)水平、肺功能(PFT)、短效β2受体激动剂使用剂量、健康相关生活质量(HRQL)评分变化.同时研究第1秒时间肺活量(FEV1)与uLTE4、HRQL评分相关性.结果 孟鲁司特组治疗后肺功能参数用力肺活量(FVC)、第1秒钟用力呼气量(FEV1)、1秒量占预计值的百分比(FEV1％pre)均较治疗前明显提高(P均＜0.05),HRQL评分均明显低于治疗前(P均＜0.01),β2受体激动剂使用剂量较治疗前显著减少(P＜0.05);治疗后孟鲁司特组uLTE4水平显著低于治疗前(P＜0.05);常规治疗组治疗前后uLTE4水平无明显改变,差异无统计学意义(P＞0.05).FEV1与uLTE4,HRQL评分均呈负相关(r分别为-0.67、-0.73,P＜0.05).结论 白三烯在慢性阻塞性肺疾病发病中可能起了重要的作用,检测尿液LTE4水平对于了解慢性阻塞性肺疾病患者体内白三烯水平,以及评价白三烯受体拮抗剂的疗效具有一定的临床意义.孟鲁司特长期使用可改善中重度稳定期COPD患者生活质量,肺功能及减少β2受体激动剂使用剂量.

自2008年起,武汉大学医学部对医学课程体系、教学方法、评价方式进行系统改革.在这轮改革中,病理学的教学形式发生了很大的改变,教学内容被整合到损伤反应和临床病理病生治疗学两门课程,本次教改已经完成完整的一轮五年医学教育.毕业问卷调查显示提高学生对病理相关的两门课程整合满意度存在差异,成绩分析显示教改班学生病理成绩显著高于传统班,尤其在理解分析题.WUMER在教学效果上实现了"加强基础,培养能力"的改革目标.

Macrophage phenotype and function varies according to their polarized state, which in turn is dependent on microenvironmental stimuli. Under normal physiological conditions, lung interstitial macrophages that express interleukin (IL)-10 are considered to serve regulatory roles in the prevention of allergic reactions in the airways. However, the phenotypic profile of lung interstitial macrophages during the pathophysiology of asthma remains unknown. In the current study, the phenotypic characteristics of lung interstitial macrophages were investigated in an ovalbumin (OVA)-induced mouse model of asthma. The patterns of surface markers chemokine ligand and interleukin, and the metabolic enzyme activity of lung interstitial macrophages were investigated using flow cytometry analysis, reverse transcription-quantitative polymerase chain reaction, western blot analysis, and ELISA. It was observed that lung interstitial macrophages derived from OVA-induced asthmatic mice expressed phenotypic markers associated with alternatively activated macrophages (M2), including cluster of differentiation-206, transglutaminase 2, arginase (Arg) 1 and chemokine ligand (CCL)17/CCL22/CCL24 secretion. The M2 macrophages also exhibited increased levels of Arg1 activity and reduced levels of IL-10 expression, relative to macrophages derived from control mice. However, when evaluating the expression of markers associated with classically activated (M1) macrophages, namely inducible nitric oxide synthase and IL-12, it was observed that levels of M1 markers in the interstitial macrophages from asthmatic mice did not differ significantly to those in controls. Collectively, these data suggest that lung interstitial macrophages undergo a phenotypic switch from a regulatory macrophage phenotype under normal conditions to an alternative activation state in OVA-induced asthmatic mice.

Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, coculture experiments, and adoptive transfer of iNKT cells in mouse models of asthma. Our data showed that iNKT cell deficiency could downregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from a mouse model of asthma. However, elevated activation of iNKT cells by α-galactosylceramide and adoptive transfer of iNKT cells could upregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from mouse models of asthma. Meanwhile, iNKT cells significantly influenced the function of LDCs, markedly enhancing Th2 responses in vivo and in vitro. In addition, iNKT cell can induce LDCs expression of CD206 and RELM-α, reflecting alternative activation of LDCs in a mouse model of asthma. α-Galactosylceramide treatment significantly enhanced expression of CD40L of lung iNKT cells from a mouse model of asthma, and the coculture experiment of LDCs with iNKT cells showed that the blockade of CD40L strongly suppressed surface maturation markers and proinflammatory cytokine production by LDCs. Our data suggest that iNKT cells can promote immunogenic maturation of LDCs to enhance Th2 responses in mouse models of asthma.

临床病理生理及治疗(clinical pathophisiology and therapy,CPPT)教学模式,即将原有的病理、病生、诊断学、内外妇儿等学科的部分或全部内容整合.病理学教学贯穿整个CPPT教学,其不仅教会学生病理学的基础知识,而且培养学生的临床思维、整合知识及解决问题的能力.文章探讨武汉大学与芝加哥大学CPPT教学模式中病理学教学的异同,以促进教师的自我学习和提高,更好地推广CPPT教学模式.

目的：探讨炎症反应与慢性阻塞性肺疾病（COPD）相关肺动脉高压及其高凝状态的关系。方法收集COPD 患者80例，根据心脏超声估测肺动脉收缩压（PASP），以 PASP 40 mmHg 为界将患者分为 COPD 伴肺动脉高压组和 COPD 无肺动脉高压组两组（每组40例），检测两组血清 C 反应蛋白（CRP）、白介素6（IL-6）、白介素8（IL-8）、肿瘤坏死因子-α（TNF-α）、脑钠肽（BNP）、D-二聚体（D-D）、纤维蛋白原（FIB）、红细胞压积（HCT），比较两组各项检测的差异，分析炎性因子与肺动脉压、D-D 的相关性以及肺动脉高压、高凝状态的影响因素。结果肺动脉高压组血清 CRP、IL-6、IL-8、TNF-α、D-D、FIB、BNP 水平高于无肺动脉高压组（P 均＜0．05）。偏相关性分析显示， CRP、IL-6、IL-8水平与 PASP 呈正相关，PaO2与 PASP 呈负相关（r 分别为0．387、0．611、0．412、－0．576，P 均＜0．05），CRP 水平与 D-D 呈正相关（r ＝0．379，P ＜0．05）。二元 Logistic 回归分析示，CRP、IL-8、TNF-α为肺动脉高压的危险因素；PaO2为其保护因素；CRP、IL-6为血液高凝状态的危险因素。结论炎症反应及其炎症因子对 COPD相关肺动脉高压及其血液高凝状态形成有重要作用。

In recent years, there has been a comprehensive reform of higher medical education in the Medicine School of Wuhan University. According to the need for reform, the teaching of neurology has to be changed from the traditional form to a new form, and be integrated into the clinical pathophysiology and therapeutics (CPPT) courses. Currently neurology in CPPT takes the form of theoretical lectures, case discussions, combined with practical lessons to observe sections under the microscope and clinical practice, for the cultivation of students'!self-learning ability and clinical thinking. In the commissioning process, it exposes some problems in teaching process due to the characteristics of the course in neurology. For example, the knowledge of neuroanatomy is insufficient and review lessons relatively too short, and the teaching effect may be worse due to the fact that teachers have busy clinic work. In addition, students participate in case discussions with less enthusiasm. To solve these problems, we take some measures to promote teaching reform in neurology, such as increasing the review hours of neuroanatomy section in the CPPT neurology, training a group of specialized medical teachers to enrich and stabilize teacher team, adjusting the content and form of discussion class to improve students'!interest and participation, and increasing assistant jobs by the student to assist discussion teaching.