Pneumocystis pneumonia constitutes a critical life-threatening opportunistic infection, where the host's immune response plays a central role in its pathogenesis. Immunocompetent individuals are typically capable of eradicating Pneumocystis without exhibiting clinical symptoms. In contrast, individuals with compromised immune systems are vulnerable to developing Pneumocystis pneumonia, which can lead to severe inflammatory responses and consequent pulmonary damage. This review examines the roles of innate immunity, particularly macrophages and adaptive immunity, including CD4+ and CD8+ T-cells, as well as key cytokines, in the defence against Pneumocystis infection across various host categories, namely immunocompetent individuals, those infected with HIV and non-HIV-infected individuals, especially those undergoing corticosteroid therapy. By integrating findings from animal models and clinical studies, this review seeks to enhance our understanding of the pathogenesis of Pneumocystis infection across varied immunological contexts.

Mortality from Pneumocystis pneumonia (PCP) continues to increase among non-human immunodeficiency virus (HIV) patients. Previous studies have reported that a considerable proportion of patients experience deterioration of their disease when glucocorticoids or other immunosuppressants are withdrawn. However, the underlying mechanisms responsible for this phenomenon remain poorly understood. Our findings, based on a comparative analysis of immune function in glucocorticoid-induced PCP mice at the time of glucocorticoid continuation and glucocorticoid withdrawal, suggested that the damage to lung tissues in PCP mice was significantly exacerbated and lung function deteriorated following glucocorticoid withdrawal. Mechanistically, our investigations revealed that PCP mice underwent immune reconstitution and developed immune reconstitution inflammatory syndrome (IRIS) after glucocorticoid withdrawal, which resulted in enhanced immune responses to pre-existing Pneumocystis. Prophylactic G-CSF neutralization in vivo prior to glucocorticoid withdrawal attenuated withdrawal-induced IRIS but also impaired Pneumocystis clearance. This study elucidated that the exacerbation of infection in PCP mice after glucocorticoid withdrawal is analogous to the clinical phenomenon and demonstrated that it is caused by the immune reconstitution that occurs after glucocorticoid withdrawal and resulting IRIS while also showing that G-CSF plays an important role in this process. This provides clinical comprehension of the progression of disease in non-HIV PCP patients.

Background Glucocorticoids have been shown to be very effective in the treatment of Human Immunodeficiency Virus (HIV) associated Pneumocystis jirovecii Pneumonia (PCP). However, risk factors and the impact on prognosis in non-HIV-PCP patients remain unclear. Our study aimed to early identification risk factors and prognostic impact of glucocorticoids therapy in non-HIV-PCP patients to decrease patients’ mortality. Methods A retrospective study was conducted on adult (≥ 18 years old) patients diagnosed with non-HIV-PCP in Peking University First Hospital from April 2007 to October 2022. A total of 269 patients with non-HIV-PCP were hospitalized during the period, and 200 patients were eventually included. Demographic data and related clinical data were collected. Univariate and multivariate logistic regression were used to analyze the relationship between variables and poor prognosis. Results A total of 200 non-HIV-PCP patients were included. 29% (58/200) patients died during admission. Univariate analysis showed that age, history of chemotherapy, history of glucocorticoid, autoimmune disease, organ transplantation, respiratory failure, platelet count, neutrophil/lymphocyte ratio, highly sensitive C-reactive protein, albumin, lactic dehydrogenase, d-dimer, bronchoalveolar lavage fluid (BALF)-neutrophil percentage, BALF-lymphocyte percentage, hospital-acquired pneumonia associated pathogen infection, pneumothorax, mediastinal emphysema, caspofungin therapy and high dose (≥ 1mg/(kg· d)) glucocorticoids therapy have a risk of death due to PCP patients. Multivariate analysis showed that age (OR = 1.062, 95%CI 1.021–1.104, P = 0.003), hospital-acquired pneumonia associated pathogen infection (OR = 4.170, 95%CI 1.407–12.357, P = 0.010) and high dose glucocorticoid therapy (OR = 7.047, 95%CI 2.482–20.006, P < 0.001) were independent risk factors for in-hospital death in non-HIV-PCP patients. Conclusions Considering the rapid course of the disease in non-HIV-infected immunocompromised patients. Early identification of high-risk PCP patients is critical to reduce morbidity and mortality. Our study found that non-HIV-PCP patients treated with high doses of glucocorticoids, old age, history of chemotherapy and hospital-acquired pneumonia associated pathogen infection had worse outcomes during hospitalization.

Background and Objective: To clarify the prevalence, features and outcomes of small airway disease (SAD) in a Chinese cohort with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) related pulmonary involvement.Methods: SAD was recorded when the manifestations of either centrilobular nodules or air trapping were observed according to CT scans, except for infection or other airway-related comorbidities. Baseline and follow-up data were collected retrospectively.Results: Of the 359 newly diagnosed AAV patients with pulmonary involvement, 92 (25.6%) had SAD, including 79 (85.9%) cases of anti-MPO-ANCA positive, 9 (9.8%) cases of anti-PR3-ANCA positive and 2 (2.2%) cases of double positive. Patients with SAD were more likely to be younger, female, non-smokers, have more ear-nose-throat (ENT) involvement, and have higher baseline Birmingham Vasculitis Activity Score (BVAS) compared to patients without SAD. Several AAV-related SAD patients have improved lung function and CT scans after immunosuppressive therapy. Patients with SAD had a better prognosis compared to those without SAD. When dividing all patients into three groups: isolated SAD (only small airway involvements), SAD with other lower airway involvements, and non-SAD, patients in the SAD with other lower airway involvements group had the highest risk of infection, while patients in the non-SAD group had the worst long-term outcomes. Similar results were observed in anti-MPO-ANCA positive patients when performing subgroup analyses.Conclusion: SAD is a unique manifestation of AAV-related lung involvement and exhibits distinct clinical features. It is vital to focus on SAD because of its association with prognosis and infection in AAV patients, especially in anti-MPO-ANCA positive patients. Moreover, SAD might represent a better response to immunosuppressors.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary Pneumocystis jirovecii pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with Pneumocystis jirovecii. Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient's oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of Pneumocystis jirovecii infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.

Acute respiratory distress syndrome (ARDS) is a collection of clinical syndromes characterized by a variety of heterogeneous causes. It includes diffuse lung diseases of various etiologies that ultimately lead to refractory hypoxia and severe acute respiratory failure. Despite advances in research and treatment of ARDS, its incidence and mortality continue to pose significant challenges in clinical practice. Since its inception in 1967, the definition of ARDS has undergone several revisions that have generated controversy and influenced the implementation of diagnostic and treatment strategies. At present, ARDS remains a formidable obstacle to both diagnosis and treatment. This article undertakes a comprehensive review of the evolution of ARDS definitions, examines the current diagnostic paradigm, and explores its far-reaching consequences. Our aim is to identify research directions, both in the realm of basic science and clinical practice, that are consistent with the nature of this complex disorder.

BackgroundCompared with Human Immunodeficiency Virus (HIV) patients, non-HIV patients with Pneumocystis pneumonia (PCP) have more rapid onset, more rapid progression, and higher mortality.ObjectivesTo investigate the predictive value of variables obtained upon hospital admission for in-hospital death and 90-day outcomes in non-HIV-PCP patients with respiratory failure (RF).MethodsThis was a single center retrospective study in a tertiary care institution over 15 years. It included all adults inpatients (≥18 years old) with laboratory confirmed non-HIV-PCP with RF who were discharged or died from Peking University First Hospital between April 1st, 2007 and November 1st, 2022. Epidemiological, clinical, laboratory, imaging and outcome data were collected from patient records.ResultsIn this study, a total of 146 non-HIV-PCP patients with RF were included. There were 57 patients (39%) died during hospitalization, 44 patients (53%) died in Intensive care unit (ICU). A total of 137 patients completed 90 days of follow-up, of which 58 (42.3%) died. The multivariable regression analysis revealed that a CD8+ T cell count <115/μl (P=0.009), bronchoalveolar lavage fluid (BALF)-neutrophil percentage ≥50% (P=0.047), the time from corticosteroids withdrawal to symptom onset ≤5 days (P=0.012), and the time from visit to initiation of sulfonamides ≥2 days (P=0.011) were independent risk factors for in-hospital death. Furthermore, a CD8+ T cell count < 115/μl (P=0.001) and the time from visit to initiation of sulfonamides therapy ≥2 days (P=0.033) was independently associated with 90-day all-cause death.ConclusionsA low CD8+ T cell count in peripheral blood, a high percentage of BALF-neutrophils, a short time from corticosteroids withdrawal to symptom onset, and a long time from visit to initiation of sulfonamides are associated with poor prognosis in non-HIV-PCP patients with RF.

IntroductionThis study seeks to explore validity and reliability evidence for core residency entrustable professional activities (CR-EPAs) that were developed by Peking University First Hospital (PKUFH) in 2020.MethodsA prospective cohort study was conducted in PKUFH. Trainers (raters) assessed pediatric residents on CR-EPAs over 1 academic year, bi-annually. Critical components within a validity evidence framework were examined: response process (rater perceptions), the internal structure (reliability and contributions of different variance sources), and consequences (potential use of a cutoff score).ResultsIn total, 37 residents were enrolled, and 111 and 99 trainers’ ratings were collected in Fall 2020 and Spring 2021, respectively. For rater perceptions, all the raters considered CR-EPAs highly operational and convenient. In all ratings, individual EPAs correlate with total EPA moderately, with Spearman correlation coefficients spanning from 0.805 to 0.919. EPA 2 (select and interpret the auxiliary examinations), EPA 5 (prepare and complete medical documents), EPA 6 (provide an oral presentation of a case or a clinical encounter), and EPA 7 (identify and manage the general clinical conditions) were EPAs correlated with other EPAs significantly. The results of the generalizability theory indicated that the variability due to residents is the highest (nearly 78.5%), leading to a large size of the reliability estimates. The matching results indicate that the lowest error locates at 5.933.ConclusionThe rating showed good validity and reliability. The ratings were reliable based on G-theory. CR-EPAs have a magnificent internal structure and have promising consequences. Our results indicate that CR-EPAs are a robust assessment tool in workplace-based training in a carefully designed setting.

Chronic obstructive pulmonary disease (COPD) is a common respiratory system disease that seriously affects the quality of life and has a high mortality rate. Exertional dyspnea is the most common symptom in COPD patients with complexed pathogenesis and limited therapeutic drug effects. In this paper, we reviewed the relevant mechanisms and assessment, in order to improve understanding of the pathogenesis of exertional dyspnea in COPD, to emphasize the importance of accurate assessment, and to explore effective interventions that can effectively improve the degree of dyspnea and even delay or reverse the decline in lung function.

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis carinii and is the most common fungal infection in HIV/AIDS patients. With the routine use of antiretroviral therapy (ART), the incidence of PCP infection in HIV/AIDS patients has decreased and the prognosis has improved significantly. On the other hand, the use of chemoradiotherapy and immunotherapy in patients with cancer, post-transplantation and autoimmune diseases are increasing dramatically, which has led to a similar increase in the incidence of PCP in these non-HIV/AIDS patients. There is a global shift in research on PCP from HIV-infected co-infected PCP (HIV-PCP) to non-HIV-infected co-infected PCP. The clinical course of non-HIV-PCP is rapid and severe, and the morbidity and mortality rates are higher than those of HIV-PCP. Studies have shown that 90% of non-HIV-PCP patients have a history of glucocorticoid use prior to infection, such as in patients with hematologic malignancies, solid organ transplants, and rheumatic diseases, and that long-term high-dose glucocorticoid use is an important risk for PCP susceptibility. Clinical practice has shown that PCP often occurs during the tapering of glucocorticoids, and a higher proportion of patients develop diffuse pulmonary lesions and, in more severe cases suffer from life-threatening acute respiratory failure. The pathogenesis of non-HIV infections associated with PCP is not yet clarified, and there is a lack of effective therapeutic practices that require further investigation.

Background: Interstitial lung disease (ILD) is a common pulmonary manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Objectives: We aimed to clarify the clinical predictors of mortality in a cohort of patients with AAV-related ILD (AAV-ILD). Method: We retrospectively identified AAV-ILD patients seen at Peking University First Hospital from January 2010 to June 2020 and manually screened for study inclusion. Baseline computed tomography (CT) images were further classified as nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), and unclassified ILD. Disease characteristics and other pulmonary findings including pulmonary function test and bronchoalveolar lavage (BAL) were also evaluated. Multivariable Cox regression analysis was performed to identify clinical predictors of mortality. Results: The cohort included 204 patients with AAV-ILD, 152 had UIP on CT (AAV-UIP), 39 had NSIP on CT (AAV-NSIP), 3 had OP, and 10 had unclassified ILD. Microscopic polyangiitis was more prevalent in patients with UIP, while granulomatosis with polyangiitis was more common in the NSIP and OP groups, and eosinophilic granulomatosis with polyangiitis was more frequent in patients with unclassified ILD. ILD diagnosis before AAV was more common in patients with either UIP or NSIP patterns. During the median follow-up of 40 months, 44 (21.6%) patients died. One- and 5-year overall survival rates were 88.2% (95% CI, 83.7–92.7%) and 81.0% (95% CI, 74.9–87.1%) for the entire cohort. Patients with UIP patterns had the worst prognosis, while those with NSIP patterns had the best long-term outcome. Specifically, patients with UIP patterns had an approximately 5-fold risk of death compared to those with NSIP. After controlling for potential confounding factors, we observed that each 10% increase in the BAL fluid neutrophil percentage was associated with nearly a 20% increased risk of death (HR 1.195, 95% CI 1.018–1.404). Conclusions: Clinical characteristics and survival differ between subgroups defined by CT patterns. BAL fluid neutrophilia is an independent predictor of mortality among AAV-ILD patients, and therefore, the clinical utility of BAL at the time of AAV diagnosis should be considered.

该文介绍了《住院医师规范化培训迷你临床演练评估指南(2022年版)》(简称《Mini-CEX指南》)发布的背景与意义,以及目前开展Mini-CEX中存在的主要问题.对指南中有关Mini-CEX的目的、组织、准备、实施、反馈及注意事项等内容进行了详细解读,以帮助指导医师在准确理解《Mini-CEX指南》?的基础上,能有效地组织和开展这种形成性评价,帮助提升教学效果,达成教学目标.

Liquid biopsy of cancers, detecting tumor-related information from liquid samples, has attracted wide attentions as an emerging technology. Our previously reported large-area PERFECT ( P recise- E fficient- R obust- F lexible- E asy- C ontrollable- T hin) filter has demonstrated competitive sensitivity in recovering rare tumor cells from clinical samples. However, it is time-consuming and easily biased to manually inspect rare target cells among numerous background cells distributed in a large area ( Φ ≥ 13 mm). This puts forward an urgent demand for rapid and bias-free inspection. Hereby, this paper implemented deep learning-based object detection for the inspection of rare tumor cells from large-field images of PERFECT filters with hematoxylin-eosin (HE)-stained cells recovered from bronchoalveolar lavage fluid (BALF). CenterNet, EfficientDet, and YOLOv5 were trained and validated with 240 and 60 image blocks containing tumor and/or background cells, respectively. YOLOv5 was selected as the basic network given the highest mAP@0.5 of 92.1%, compared to those of CenterNet and EfficientDet at 85.2% and 91.6%, respectively. Then, tricks including CIoU loss, image flip, mosaic, HSV augmentation and TTA were applied to enhance the performance of the YOLOv5 network, improving mAP@0.5 to 96.2%. This enhanced YOLOv5 network-based object detection, named as BALFilter Reader, was tested and cross-validated on 24 clinical cases. The overall diagnosis performance (~2 min) with sensitivity@66.7% ± 16.7%, specificity@100.0% ± 0.0% and accuracy@75.0% ± 12.5% was superior to that from two experienced pathologists (10–30 min) with sensitivity@61.1%, specificity@16.7% and accuracy@50.0%, with the histopathological result as the gold standard. The AUC of the BALFilter Reader is 0.84 ± 0.08. Moreover, a customized Web was developed for a user-friendly interface and the promotion of wide applications. The current results revealed that the developed BALFilter Reader is a rapid, bias-free and easily accessible AI-enabled tool to promote the transplantation of the BALFilter technique. This work can easily expand to other cytopathological diagnoses and improve the application value of micro/nanotechnology-based liquid biopsy in the era of intelligent pathology.

胜任力评价是胜任力导向医学教育重要的组成部分.在胜任力导向住院医师培训项目中,临床胜任力评估委员会(Clinical Competence Committees,CCCs)是其重要的组成部分.CCCs作为决策小组,定期(通常半年一次)根据住院医师的各种评估数据,遵循程序化评估原则,综合判断住院医师胜任力的成长情况,从而与住院医师项目主任一起,确定住院医师合理的里程碑评级、发展轨迹与进一步改进建议,确保住院医师规范化培训结业时,能够达到独立执业的要求.该文将借鉴国际CCCs经验与现况,介绍北京大学第一医院儿科住院医师项目CCCs的架构、职责和运行经验,讨论存在的问题,提出未来进一步改进的设想.

基于BALF的液态活检能够从细胞和分子层面提供病变信息，可以克服影像学检查难以确诊、组织活检取样技术复杂且困难等问题，有助于肺结节性质的早期判定，对优化肺结节的诊断流程具有重要意义。本文探讨BALF的肺癌液态活检技术对肺结节性质鉴别的价值，分析不同方法的优势、局限性和应用过程的注意事项，思考相关技术未来的发展方向并提出建议，以期促进前沿技术与现有临床诊断模式的有机结合，有望为肺癌的早期诊断提供有力帮助。

该文介绍了《住院医师规范化培训SOAP病例汇报评估指南(2022年版》(简称《SOAP病例汇报评估指南》)的发布背景与意义,阐述了主观-客观-评价-计划(subject-objective-assessment-plan,SOAP)病例汇报评估的起源以及应用实践中的主要问题,对SOAP病例汇报评估的内容以及评估表进行了解读说明,并就SOAP病例汇报评估应用中的重点问题进行讨论,以帮助指导医师在深入理解《SOAP病例汇报评估指南》的基础上,有效地组织实施SOAP病例汇报评估教学活动,提升教学效果,达成教学目标.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder characterized by chronic bronchitis, emphysema, or both. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has had a tremendous impact on the diagnosis and treatment of COPD. This article reviewed the evolution of the definition of COPD in GOLD and the change of its treatment strategy. In addition, in light of relevant clinical studies, the paper attempted to illustrate the importance of understanding the heterogeneous nature of COPD, and analyzed the possible consequences of ignoring this nature, including confusion with bronchial asthma caused by lung function as the "gold standard" and excessive use of inhaled glucocorticoids (ICS). It is suggested that in clinical practice, the essential characteristics of COPD patients should be clarified by collecting a variety of information in order to provide personalized treatment for patients' assessment, therapy and rehabilitation. At the same time, more basic and clinical research on COPD should be conducted, based on the nature of the disease, to explore new treatment methods.

过程考核作为住院医师规范化培训制度建设的重要组成部分,是一项正在探索和实践的重要工作.本文介绍了住院医师规范化培训过程考核的重要性、内涵、工作进展与成效、考核结果应用、存在的问题和应对策略.

教学法是实施教学实践的一套原则和方法.它受社会、政治等外在要素的影响,同时又从外部环境中选取资源、工具等教学要素,安排和组织教学过程.互联网带来的教育数字化转型,正在从外部生态环境,以及内在的教学构成要素两方面,推动教学实践和教学法知识体系的数字化转型.美国现代语言协会于2020年在线正式出版的《人文学科中的数字教学法》就是在这种数字生态环境下,出版的一种数字时代的教学法知识体系,以及一种教学法的数字教材(合集).该教材的编写历时10多年时间,有近800位作者参加编写,征集了573个优质"教学构件"案例,用59个关键词、24类教学构件、79种标签等"元数据"把这些优秀案例编织在一起,形成了一部教师可以分叉、重混使用的"数字教学法"新型教材.该教材在教学法理念和教材形态两方面进行的开拓性探索,对中国教育教学的数字化转型、新型教材建设等,都具有重要启示和借鉴意义.