Immune checkpoint inhibitors (ICIs) play a significant anti‑tumor role in the management of non‑small cell lung cancer. The most broadly used ICIs are anti‑programmed death 1 (PD‑1), anti‑programmed cell death‑ligand 1, and anti‑cytotoxic T lymphocyte‑associated antigen‑4 monoclonal antibody. Compared with traditional chemotherapy, ICIs have the advantages of greater efficiency and more specific targeting. However, the resulting immune‑related adverse events limit the clinical application of ICIs, especially checkpoint inhibitor pneumonitis (CIP). CIP chiefly occurs within 6 months of administration of ICIs. Excessive activation and amplification of cytotoxic T lymphocytes, helper T cells, downregulation of regulatory T cells, and over‑secretion of pro‑inflammatory cytokines are the dominant mechanisms underlying the pathophysiology of CIP. The dysregulation of innate immune cells, such as an increase in inflammatory monocytes, dendritic cells, neutrophils and M1 polarization of macrophages, an increase in IL‑10 and IL‑35, and a decrease in eosinophils, may underlie CIP. Although contested, several factors may accelerate CIP, such as a history of previous respiratory disease, radiotherapy, chemotherapy, administration of epidermal growth factor receptor tyrosine kinase inhibitors, PD‑1 blockers, first‑line application of ICIs, and combined immunotherapy. Interestingly, first‑line ICIs plus chemotherapy may reduce CIP. Steroid hormones remain the primary treatment strategy against grade ≥2 CIP, although cytokine blockers are promising therapeutic agents. Herein, the current research on CIP occurrence, clinical and radiological characteristics, pathogenesis, risk factors, and management is summarized to further expand our understanding, clarify the prognosis, and guide treatment.
间质性肺病( ILD)是一组主要累及肺泡及周围组织和肺间质,以慢性炎症及间质纤维化为主,具有相似的影像学、病理学和临床表现特点的肺脏薄壁组织炎症性疾病.目前ILD的分类采用2002 年美国胸科学会( ATS)和欧洲呼吸学会( ERS)推荐的分类方法〔1〕.其中,结缔组织病( CTD)是继发性ILD的首要基础疾病.CTD相关的ILD( CTD-ILD)患者多为老年人,有报道证实年龄较大、吸烟暴露等是CTD患者并发ILD 的已知危险因素〔2〕.由于老年患者的机体免疫力低下、易并发感染及治疗药物副作用等因素,导致随着年龄增加,CTD-ILD患者的急性加重次数、疾病严重程度、住院率和死亡率等也明显升高〔3,4〕.同时,有研究表明CTD-ILD 患者的直接医疗保健,老年护理和间接成本明显高于CTD不伴ILD患者,严重增加了医疗资源消耗、个人及社会经济负担〔5,6〕.目前CTD-ILD的发病率及死亡率较高,且治疗措施有限,因此早期诊断、尽早干预对改善患者预后、提高患者生活质量、减轻家庭及社会负担意义重大.CTD-ILD具有发病隐匿、临床表现缺乏特异性、发病率高等特点,诊治难度大,仅根据临床征象很难诊断,需结合多种相关辅助检查.目前临床上诊断CTD-ILD主要依靠高分辨率( HR ) CT、肺活检和肺功能检测等.
Objectives: To assess the effects of corticosteroid therapy for patients with severe coronavirus disease 2019 (COVID-19). Methods: We comprehensively searched articles published in the Cochrane Library, PubMed, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases from January 1, 2019, to March 20, 2021. Results: A total of 6771 patients from eight prospective studies were included in our meta-analysis. The results showed that corticosteroid therapy was associated with lower mortality in severe COVID-19 (OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; I-2 = 54.5%). Since the proportion of the RECOVERY (Randomized Evaluation of COVID19 Therapy) trial included in the meta-analysis was as high as 71.88%, we removed it and recalculated the pooled OR. The results of the remaining seven studies still suggested such a survival benefit (OR = 0.65, 95% CI = 0.44-0.96, P = 0.030; I-2 = 59.8%). Furthermore, subgroup analysis suggested that the pooled OR of three studies using corticosteroids in the early stages of treatment was much lower (OR = 0.37, 95% CI = 0.25-0.57, P < 0.001; I-2 = 47.8%). However, after excluding the RECOVERY trial, the pooled OR of the remaining four studies with unspecific administration timing of corticosteroid therapy no longer supported this result (OR = 0.90, 95% CI = 0.69-1.17, P = 0.415; I-2 = 0.0%). Conclusions: In this meta-analysis, evidence based on seven randomized controlled trials and one prospective cohort study indicates that corticosteroid therapy was associated with a reduction in the mortality of severe COVID-19, especially when administered at an earlier time.
Background: We aimed to describe the clinical features of novel coronavirus disease 2019 (COVID-19) patients with or without diabetes, focusing on the effect of abnormal HbA1c levels on inflammatory reactions and disease severity.Methods: A total of 190 patients with COVID-19 were included in this cross-sectional study. Clinical and laboratory characteristics were collected and compared among moderate, severe, and critical cases, as well as among diabetes, prediabetes and nondiabetes cases. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic ability of HbA1c for disease severity. Logistic regression was used to explore the relationship between HbA1c levels and worse prognosis of COVID-19.Results: HbA1c levels at admission were significantly different in patients with moderate, severe, and critical diseases (P<0.001). The area under the curve (AUC) of HbA1c levels to distinguish between moderate and severe-critical diseases was 0.938 (95% CI 0.906–0.970). After adjustment for confounders, the results showed that the increasing odds of in-hospital deaths were associated with HbA1c levels >6.0% (42 mmol/mol) (aOR 2.971 [95% CI 1.002, 8.804], P=0.049), and the increasing odds of severe or critical COVID-19 were associated with HbA1c levels ≥5.7% (39 mmol/mol) (aOR 29.588 [95% CI 8.285, 105.457], P<0.001). In addition, HbA1c levels strongly correlated with inflammatory markers and cytokines.Conclusions: Abnormal glucose metabolism can cause a hyperinflammatory state of COVID-19, which manifests as severe disease.
目的 探讨分析以案例库为基础的早期临床医学教育模式在呼吸内科学生实践教学中的具体应用及教学效果.方法 根据教学大纲编写呼吸内科案例库,以吉林大学白求恩医学部2012级临床五年制实习学生60名(采用案例库早期导入教学模式)与2011级临床五年制实习学生63名(采用传统教学模式)为研究对象,对2组学生及授课教师进行调查问卷及成绩分析.结果 建立完成了集文字图片影像于一体的呼吸内科案例库,包含24个呼吸系统典型疾病案例,案例库早期导入教学模式可以提高学生临床学习兴趣;提高学生早期临床思维能力,缩短学生从理论过渡到临床实践的时间;可以提升教师授课水平,提高教学质量,提高教师的教学热情.结论 在呼吸内科教学中早期导入案例库教学方法优于传统的教学方法,适于推广及扩大教学.
标准化病人在临床模拟教学中具有广泛的应用前景,但在人员的招募、培训、考核及应用中受到许多条件的限制,难以普及,通过分析吉林大学第二医院标准化病人团队的建设,总结其在标准化病人的招募、培训、选择、考核及应用中的经验,以期为本科生临床模拟教学中广泛开展标准化病人教学提供更多的参考.
We aim to investigate whether microRNA-106b (miR-106b) affects the inflammation injury of cardiac endothelial cells (ECs) by targeting B-cell linker (BLNK) via the NF-κB signaling pathway. Human cardiac microvascular endothelial cells (HCMECs) were assigned into the control, hypoxia/reoxygenation (H/R), negative control (NC), pyrrolidine dithiocarbamate (PDTC), miR-106b mimic, miR-106b inhibitor, and si-BLNK, and miR-106b inhibitor+si-BLNK groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted for miR-106b expression and expressions of BLNK, interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, NF-κB, pIκBα, BTK, and PLC-γ2. Enzyme-linked immunosorbent assay was applied for levels of IL-6, IL-10, and TNF-α; cell counting Kit-8 assay for cell proliferation; and flow cytometry for cell cycle and ensuing apoptosis. In-vitro tube formation assay was performed for tube formation ability. Dual-luciferase reporter assay revealed that BLNK was verified as the target gene of miR-106b. Compared with the H/R and NC groups, the PDTC, miR-106b mimic, and si-BLNK groups had declined expressions of IL-6, IL-1β, TNF-α, BTK, PLC-γ2, NF-κB p105/p50, and pIκBα as well as levels of L-6 and TNF-α, but contrarily elevated levels of NF-κB p105/p50 and IL-10. The PDTC, miR-106b mimic, and si-BLNK groups had less cell number in G0 /G1 phase but higher cell count in both S and G2 phases, decreased cell apoptosis but increased proliferation and tube formation ability, while opposite trends were observed in the miR-106b inhibitor group. Our findings indicated that the overexpression of miR-106b alleviated the inflammation injury of cardiac ECs by targeting BLNK via the NF-κB signaling pathway.
LncRNA H19 is involved in the development of multiple cancers. Here, we firstly provide new evidence that H19 can induce LIN28B, a conserved RNA binding protein, to accelerate lung cancer growth through sponging miR-196b. Abundance in LIN28B was observed in clinical lung cancer samples. A positive link was observed between H19 and LIN28B in clinical lung cancer samples. In lung cancer cells, H19 was capable of increasing LIN28B expression. Mechanistically, miR-196b directly targeted LIN28B to inhibit LIN28B expression. H19 was capable of promoting LIN28B expression through sequestering miR-196b. Functionally, H19-increased LIN28B conferred the cell proliferation of lung cancer. Our finding indicates that H19 depresses miR-196b to elevate LIN28B, resulting in accelerating cell proliferation in lung cancer.
A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in this study were aimed at confirming the role of the gene product in PAM by comparing phosphorylated products in extracellular fluid of alveolar epithelial cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic expression vectors were constructed and transfected into A549 human alveolar epithelial cells. There were three groups of cells including those transfected with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and those transfected with a version of the PAM SLC34A2 gene linked to the pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the concentration of inorganic phosphorus in the culture medium was detected using an automatic biochemical analyzer. Our results showed the concentration of inorganic phosphorus in the supernatant of the normal control group was significantly lower than that in the plasmid control and PAM groups (P<0.01), and the concentration in the PAM group was significantly lower than that in the plasmid control group (P<0.01). Based on our findings it is possible that the SLC34A2 gene mutation is the cause of the pathogenic changes observed in PAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations in vivo.
随着现代医学模式的转变,医学生的教育对于医学人文素质的培养更加重视,而目前中国的医学教育仍然存在着重理论与技能的培训,轻医学人文素质培养的问题.除了通过开设医学伦理道德的理论课程外,建立标准化病人的课程能够更直接的通过模拟医患交流达到提高医学生医学人文素质的目的.在建立标准化病人的课程体系时,在设计病例时注重加入病人特定心理因素、民族文化背景等社会心理因素,更加重视如何帮病人解决自身问题,建立良好的医患关系,增加医学生在真正进入临床实习时的自信心.并通过培训非医务人员的标准化病人,建立一批固定的标准化病人群,做到1个标准化病人只熟练掌握1个特定病例,做到最接近真实病人状态的模拟,使医学生在进入临床实习前培养良好的医患关系及处理临床问题的能力.
住院医师是医院各项工作的生力军、后备力量.医学生毕业之后以住院医师身份接受比较科学、系统的规范化培训,通过培训使其具备牢固的基本理论知识及掌握基本技能.扎实的基本技能是住院医师在未来行医生涯中极为重要的职业工具,加强基本技能的培训成为住院医师规范化培训十分重要的部分.该文分析了住院医生规范化培训的现状,提出制定临床技能培训计划.通过使用临床技能培训中心,加强住院医师各项基本技能的熟练程度减少在实际病人操作中出现的问题,为住院医师基本操作技能的提高提供了帮助.并且加强临床实践技能考核,提高住院医师临床工作能力.
Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes and results in high mortality. It is therefore imperative to develop novel therapeutics for the prevention or inhibition of the progression of DCM. Oxidative stress is a key mechanism by which diabetes induces DCM. Hence, targeting of oxidative stress-related processes in DCM could be a promising therapeutic strategy. To date, a number of studies have shown beneficial effects of several natural products on the attenuation of DCM via an antioxidative mechanism of action. The aim of the present review is to provide a comprehensive and concise overview of the previously reported antioxidant natural products in the inhibition of DCM progression. Clinical trials of the antioxidative natural products in the management of DCM are included. In addition, discussion and perspectives are further provided in the present review.
Objective:To introduce the clinical characteristics,diagnosis and treatment experience of one case of acute respiratory tract obstruction and review the relevants literature to heighten the understanding of tracheal mucosa associated lymphoid tissue lymphoma,and to provide a feasible way to reduce the acute dyspnea.Methods:Bronchoscopic examination,local tissue biopsies,and the treatment of argon plasma coagulation and cryosurgery were performed in the patient with acute dyspnea.After the treatment the patients was treated with local radiotherapy.Results:The dyspnea of patient was significantly impoved.The pathological results showed tracheal mucosa associated lymphoid tissue lymphoma which was also called non-Hodgkin's lymphoma.The tracheal has no stenosis under bronchoscope.Conclusion:The primary tracheal mucosa associated lymphoid tissue lymphoma is very rare.The local tissue biopsies under fiberoptic bronchoscope is the main diagnostic method.Bronchoscopic argon plasma coagulation and cryosurgery which is convenient and small traumatic can ease the patients with acute dyspnea,its combination with radiotherapy,chemotherapy or immunochemical therapy is suitable treatment for the tracheal mucosa associated lymphoid tissue lymphoma and other tracheal neoplasms.
Haze weather is becoming one of the biggest problems in many big cities in China. It triggers both public anxiety and official concerns. Particulate matter (PM) plays the most important role in causing the adverse health effects. Chemical composition of PM2.5 includes primary particles and secondary particles. The toxicological mechanisms of PM2.5 to the human body include the oxidative stress, inflammation and carcinogenesis. Short or long-term exposure to PM (especially PM2.5) can cause a series of symptoms including respiratory symptoms such as cough, wheezing and dyspnea as well as other symptoms. There are positive associations between PM2.5 and mortality due to a number of causes. PM2.5 is considered to contribute to the onset of asthma, the exacerbation of chronic obstructive pulmonary disease (COPD) in haze weather. Some approaches including outdoor health care, indoor health care and preventive medications can prevent the patients with chronic airway diseases from exacerbations.
No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China.
Objective:Examined the impairment of regulatory T cells in cord blood from offspring of allergic asthmatic mothers. Methods:Cord blood mononuclear cells from 62 healthy neonates(40 healthy mothers and 22 allergic asthmatic mothers) were isolated,and cultured with stimuli: lipid A(TLR4 ligands),peptidoglycan(Ppg-TLR2 ligands),mitogen(PHA,phytohemagglutinin) and Dermatophagoides pteronyssinus1.And then the amount of CD4+CD25+Foxp3+T cells was acounted with flow cytometry;cytokine concentrations were measured in supernatants by LUMINEX technology;the suppressive function of regulatory T cells were examinated by isolating and culturing of CD4+CD25+T cells and CD4+CD25-T cells in vitro. Results:Cord blood from offspring of allergic asthmatic mothers showed Ppg-induced fewer regulatory T cells(CD4+CD25+Foxp3+T,P=0.03) and lower IL-10 secretion(P=0.03).Furthermore,the suppressive capacity of regulatory T cells was impaired in PHA-induced division and proliferation of T effector cells in cord blood of offspring from allergic asthmatic mothers(P=0.05).Meanwhile,the suppressive capacity of regulatory T cells to IL-13 production by effector cells was partially impared(P=0.07). Conclusion:In offspring of allergic asthmatic mothers,regulatory T cells amount,and suppressive function were impaired at birth,which maybe potentially contribute to the the susceptibility to allergic diseases.
SESSION TITLE: Diffuse Lung Disease SESSION TYPE: Case Report Poster PRESENTED ON: Sunday, April 17, 2016 at 11:45 AM - 12:45 PM INTRODUCTION: Broncholithiasis is a rare condition on clinic. It refers to the condition that the component of calcification or ossification appear in the lumen of bronchus. The patient with broncholithiasis may have no symptoms and also can have series of symptoms including cough, dyspnea, chest pain or hemoptysis. Because it is a rare condition, many doctors may ignore it and make a wrong diagnosis. CASE PRESENTATION: A 46 years old female patient, complained of chest pain, cough and sputum for three months. She felt right chest pain three months ago, the pain was persisting. She had coughing and large amount of white sputum. Two months ago she was diagnosed with pneumonia and treated with amoxicillin for 1 week but the symptoms were not relieved. One months ago, she coughed up some whtie material like stone. The shape of the stone is irregular, the diameter is about 5mm. Five days ago she had severe cough and yellow sputum and then came to our hospital. PE: The chest wall was symmetrical, percussion note was resonance, the breath sound was normal and no rales in alscultation. Blood rountine test: WBC 9.6×109/L, percentage of eosinophil was 10.8%. Blood coagulation is normal. Serum tests including hepatic function and renal function were normal. Chest CT scanning showed the infiltration in the right middle lobe, and calcification near the right middle bronchial, and the calcificated lymph node in the mediastinum. The results under the fibre bronchoscope showed the ulceration in the right middle bronchial. The results of acid-fast bacilliin sputum and BALF sample were negative. After the treatment of antibiotics, the patient was recovered. DISCUSSION: The probability of broncholithiasis in respiratory diseases account for 0.1%-0.2%. Broncholithiasis is more seen in the right bronchial than in the left, and this is related to the anatomy of the bronchials, the right bronchial is easier to be affected by the calcificated lymph node. In China, the most common reason for broncholithiasis is pulmonary tuberculosis. The most common symptom of this condition is dry cough. Some patients may have fever, chest pain and hemoptysis. Chest CT scan is better in the diagnosis than X-ray. The treatment include observation, moving the stone through fibre bronchoscope and surgery. CONCLUSIONS: Although broncholithiasis is rare, when the patients have hemoptysis and dyspnea especially with the history of pulmonary tuberculosis and calcificated lymph node, broncholithiasis should be taken into account. Reference #1: Patompong U, Narat S, Michael A. B, Lee C. E. Broncholithiasis: An Uncomm on Cause of Chronic Cough. J. Bronchol Intervent Pulmonol.2014:21:1. Reference #2: Anwer M, Venkatram S. Broncholithiasis: "incidental finding during bronchoscopy"—case report and review of the literature. J Bronchol Intervent Pulmonol. 2011;18:181-183. Reference #3: Mayuri A Kamble, Anand P Thawait, Ashok T Kamble. Rare presentation of bronchiectasis with multiple bronchial stones. Scottish Medical Journal.2015, Vol. 6 0 (1) e14-e18. DISCLOSURE: The following authors have nothing to disclose: Jin Ren, Tiangang Ma, Jinzhi Yin, Rong Gao No Product/Research Disclosure Information
Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. However, the mechanisms that underlie these risk factors remain poorly defined. Therefore, the aim of this study was to assess whether maternal allergies affect the Tregs of offspring and lead to allergy development in childhood.