2018年 · 第41卷第09期

Why is there no COPD without lung function? Professor Liu Youning, editor-in-chief of this journal, in his essay "Random Talk about Pulmonary Function Measurement and Chronic Obstructive Pulmonary Disease" from FEV₁and FEV₁/The relationship between FVC and COPD was discussed from two angles, and it was believed that respiratory doctors engaged in the field of COPD must have a comprehensive and thorough understanding of the principle, technology and clinical interpretation of pulmonary function measurement.

In the author's opinion, chronic obstructive pulmonary disease (COPD) is not a single disease, but airflow obstruction syndrome that excludes other known causes. Even the definition itself is inseparable from lung function. It can also be said that there is no COPD without lung function test. The results of lung function test are of absolute value to judge whether COPD is or not and the severity of the disease. Obstruction in COPD refers to airflow obstruction, that is, the term of lung function equivalent to obstructive ventilation disorder. Mild obstruction may not have any clinical symptoms and signs, even wheezing and dyspnea caused by severe obstruction, if there is no lung function measurement, it is difficult to distinguish from other diseases. Therefore, respiratory doctors, especially medical workers who focus on the field of COPD, must have a comprehensive and thorough understanding of the principle, technology and clinical interpretation of pulmonary function measurement, and preferably have practical experience.

Respiratory doctors mostly believe that infection is local or systemic damage caused by pathogenic pathogens such as bacteria, viruses, fungi and parasites invading the human body. They pay more attention to pathogens and their pathogenicity, and pay less attention to the response of infected hosts to pathogens and their related problems. In 2016, Sepsis 3.0 jointly promulgated by the American Society of Critical Care and the European Society of Critical Care pointed out that severe infection is a life-threatening organ dysfunction caused by the host's uncontrolled response to infection, focusing on the impact of the host's unbalanced response due to infection on the occurrence and development of disease^[1]。 The existing research results show that in the state of severe infection, pathogen associated molecular patterns (PAMP) continuously stimulate the body's immune system, which causes the innate and adaptive immune systems to be overactivated, the pro-inflammatory response and anti-inflammatory response are imbalanced, and lymphocytes are consumed and apoptosis, resulting in abnormal innate immune function and adaptive immune dysfunction^[2]。 In addition to the pathogen, we should pay attention to the immune imbalance secondary to the inflammatory response, which is an important feature of the pathophysiological process of severe infection, and is the main cause of aggravation and even death of patients with severe infection^[3]。

In 2016, the American Society for Critical Care and the European Society for Critical Care developed a new definition and diagnostic criteria for sepsis, considering sepsis to be a life-threatening organ dysfunction caused by a dysregulated host response to infection^[1]。 Early diagnosis of sepsis is difficult and the overall mortality rate is high. Early recognition of sepsis and anti-infection is an important measure for sepsis treatment, and over-emphasizing early application of antimicrobial drugs may be a double-edged sword. On the one hand, some researchers believe that broad-spectrum antibacterial drugs should be applied within 3 hours of the patient's medical treatment, otherwise it may aggravate organ dysfunction and reduce the degree of organ recovery^[2]； On the other hand, time-limited application of antimicrobial drugs to patients with suspected sepsis may lead to overuse of antimicrobial drugs or even inappropriate initial treatment^[3]。 The latest guidelines still recommend starting effective intravenous antimicrobial therapy within 1 h of diagnosis of sepsis or septic shock^[1,4]But the evidence is insufficient. Therefore, the best time for antimicrobial treatment of patients with suspected sepsis is still the key link in the treatment of sepsis.

Sepsis, defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, is an important cause of death^[1]。 Septic shock is a special type of sepsis, with severe circulatory disorders and abnormal cellular metabolism, resulting in a large increase in mortality^[1]。 With the aging of the population, the widespread application of invasive medical methods and immunosuppressants, the incidence of sepsis is increasing, which is one of the important problems faced in clinical work. Microcirculation dysfunction is one of the important causes of organ dysfunction and death in sepsis patients. Early identification of tissue hypoperfusion is crucial for developing reasonable hemodynamic support protocol and preventing irreversible organ damage. The presence or absence of tissue hypoperfusion in patients with sepsis can be determined by clinical manifestations, blood lactate levels, and tissue oxygen supply/consumption (oxygen delivery/oxygen consumption, DO₂/VO₂) to make clinical discrimination.

Sepsis is a highly heterogeneous clinical syndrome that is currently defined as life-threatening organ dysfunction caused by the dysregulation of the body's response to infection. This high heterogeneity of sepsis suggests that there is no static "treatment package" in clinical practice, but that individualized, phased and targeted (targeted) treatment strategies should be adopted according to different individuals and different pathophysiological stages of sepsis. It is an important means for individualized and targeted therapy of sepsis to screen out characteristic biomarkers from different pathophysiological stages and then intervene targetedly. Sepsis biomarkers have many functions, and their specific clinical applications mainly include: (1) diagnosis, such as obvious elevation of procalcitonin (PCT) often indicates systemic bacterial infection; (2) stratification, i.e. screening by biomarkers that patients with some or some pathophysiological characteristics, such as patients with reduced expression of monocyte human leukocyte antigen-DR (HLA-DR), may be suitable for immunostimulatory therapy; (3) organ function monitoring, such as high level of angiopoietin (Ang) 2 often indicates serious vascular endothelial damage; (4) Prognostic judgment, for example, the level of monocyte programmed death ligand (PDL) 1 in sepsis patients is significantly correlated with mortality. Up to 200 kinds of sepsis biomarkers have been discovered, but only a few dozen have preliminary research results and/or clinical application prospects. It can be seen from the definition of sepsis that sepsis consists of three aspects: infection, dysregulated host response and organ dysfunction that are closely related. Theoretically, biomarkers reflecting these three aspects can guide the individualized treatment of sepsis or serve as potential therapeutic targets. Combined with the pathophysiological characteristics of sepsis, several biomarkers are introduced from the aspects of infection, organ dysfunction, inflammation activation and immune imbalance. It should be pointed out in particular that at present, no biomarker is absolutely reliable. Only by combining the clinical manifestations of patients and other laboratory tests and comprehensive analysis can a reasonable and correct judgment be made.

The problems involved in sepsis include inflammation initiation and amplification, vascular endothelial damage, platelet activation and aggregation, and imbalance of coagulation factors, etc. Among them, inflammation and coagulation are inseparable, and there are complex interactions. "Anticoagulation or anti-inflammation" is always an inevitable problem in anticoagulation treatment of sepsis. The trend of coagulation dysfunction in sepsis patients is an important determinant of disease development. "To resist or not to resist? When to resist? What drugs to resist?" runs throughout the anticoagulant therapy of sepsis.

Tuberculosis is one of the important public Health problems that threaten human Health. According to the World Health Organization (WHO), there were approximately 10.4 million new cases of tuberculosis worldwide in 2016, of which 1.67 million died from tuberculosis^[1]。 Especially since 2018, with the increasing number of patients with multidrug-resistant tuberculosis (MDR) and extensively drug-resistant tuberculosis (XDR), the prevention and control of tuberculosis has faced unprecedented challenges^[2,3]。 China is one of the 30 countries with a high burden of tuberculosis in the world, with 895,000 new tuberculosis patients every year, ranking third in the world; 58,000 cases of multidrug-resistant tuberculosis, ranking second in the world^[1]Therefore, tuberculosis has become one of the major public problems restricting the social and economic development of our country^[4]。 Early diagnosis, early isolation and early treatment are the key links to reduce the incidence and death of pulmonary tuberculosis. The delay in diagnosis leads to the delay of individualized treatment and Mycobacterium tuberculosis (Mycobacterium tuberculosis, MTB) propagation of^[5,6]。 Laboratory diagnosis of tuberculosis is an important way to find tuberculosis patients. Sputum smear examination is cheap and easy to operate, but its sensitivity is not high; Sputum culture has high sensitivity and has been used as the gold standard for laboratory diagnosis of tuberculosis. However, its detection cycle is too long, and it cannot provide timely detection results for clinical practice^[7,8,9]。 In view of the many shortcomings of existing bacteriological tests, the WHO revised the diagnostic criteria for tuberculosis in 2013^[10]Patients who test positive by molecular biology methods are included in the category of etiological positivity. China also revised the diagnostic criteria for pulmonary tuberculosis in 2017. In this criteria, positive molecular biology diagnosis is used as the diagnostic basis for positive etiology^[11]。 Although the timeliness of molecular biology diagnostic technology is better than that of traditional methods, it is a difficult problem for clinicians to correctly and comprehensively interpret the molecular biology diagnostic report of tuberculosis, especially when the results of molecular diagnostic technology and traditional diagnostic technology are inconsistent. How to make better use of molecular biology diagnostic report for clinical diagnosis is a difficult problem. In order to better understand the diagnostic criteria of the new version of the guidelines and improve the ability of tuberculosis diagnostic personnel to interpret the laboratory results of molecular biology diagnostic technology, the Clinical Laboratory Professional Committee of Tuberculosis Branch of Chinese Medical Association organized experts in laboratory and clinical fields to discuss important issues in the field of molecular biology diagnostic technology, and wrote this consensus.

A 77-year-old male was admitted to the 306th Hospital of the People's Liberation Army in Beijing on December 13, 2016 due to "cough and blood in sputum for 15 days". The patient had a small amount of bloody sputum at the beginning of the disease, which was not paid attention to, and then the amount of sputum and blood gradually increased to come to the diagnosis. The patient had no accompanying symptoms such as fever, chest pain, chest tightness and dyspnea during the course of the disease. Previous smoking history, smoking index 40 pack years. With a history of hypertension for more than 30 years, the blood pressure was controlled at about 140/95 mmHg (1 mmHg =0.133 kPa) when treated with oral levamlodipine besylate. Outpatient chest CT showed a mass in the proximal aortic arch of the left upper lobe (Figure 1), considering the lung space and the possibility of lung cancer, it was recommended that he be hospitalized for CT-guided percutaneous lung biopsy to further confirm the diagnosis, but the patient refused. Hemoptysis disappeared spontaneously after 1 week, but there was chest tightness, shortness of breath and fever after activity, and the maximum body temperature was 38.5 ℃ without chills. He was admitted to the Department of Respiratory Medicine on December 20, 2016.

Protein S deficiency is a less common hereditary thrombotic disorder, first reported in 1984. In recent years, reports of this defect have been seen one after another at home and abroad, and deep vein thrombosis of lower limbs is the common symptom. A confirmed case of hereditary protein S deficiency with a wide range of thrombus involvement and pulmonary thromboembolism is reported below.

Sepsis is a common systemic severe infectious disease in clinic, which can be complicated by septic shock, acute kidney injury (AKI), acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS) and other serious complications. About 4 million patients die from sepsis worldwide every year, and its incidence is increasing year by year^[1]。 Inflammatory response, immune response, coagulation dysfunction and other factors constitute the complex regulatory network of sepsis, and its pathogenic mechanism has not been fully elucidated^[2,3]。

Intermediate fibers, microtubules and microfilaments together form a cell scaffold network to maintain the integrity of cells. vimentin (VIM) is the most important intermediate fiber structure in interstitial cells, and its significance in the process of disease development has been more and more recognized. The gene encoding human undulating protein is located on chromosome 10p13. Its DNA is about 10 kb in length, cDNA is 1 848 bp in length, contains 9 exons, and the open reading frame is 1 401 bp. The undulating protein consists of 464 amino acid residues and has a relative molecular mass of about 57×10³Da. From invertebrate to vertebrate species, the sequence of undulating protein is highly consistent, indicating that it is highly conserved in evolution. At present, the main functions of undulated proteins have been found^[1]: (1) participate in constituting cell engagement and regulating cell adhesion and cell migration; (2) participating in cell signal transduction; (3) regulating apoptosis; (4) Regulating the expression of genomic DNA. Sepsis is considered to be a severe infection affecting organ function, and its pathogenesis is complex and unclear at present, considered to be associated with cascade amplification of inflammation and imbalance of immune response^[2]。 Whether vimentin will become an important new mechanism in the pathogenesis of sepsis, this review summarizes the relationship between vimentin and bacterial infection, the relationship between vimentin and inflammatory response, the possible role of vimentin in sepsis, the possible signaling pathway by which vimentin plays a role, and the possible role of vimentin in immunomodulation in sepsis.

pulmonary embolism (PE) is a potentially life-threatening cardiovascular disease^[1]Its symptoms and signs are similar to those of many diseases, which can easily lead to missed diagnosis and misdiagnosis^[2]。 So far, pulmonary embolism is still the most common cause of death without definite diagnosis before death. Even after multi-slice CT, the accuracy of the diagnosis of pulmonary embolism before death is only 59%^[3]。 Therefore, early diagnosis and timely treatment of pulmonary embolism are particularly important to improve the prognosis of patients. At present, computerized tomography pulmonary angiography (CTPA) has become the first-line imaging test for the diagnosis of pulmonary embolism. Combined with the clinical possibility assessment, the incidence of venous thromboembolism after 3 months follow-up is only 0.6%, which can safely rule out pulmonary embolism^[4]。 However, there are some inevitable problems in CTPA examination: such as high examination cost, the use of contrast medium may cause allergic reactions and kidney damage, and radiation exposure will increase the risk of tumor. In contrast, ultrasound examination has the advantages of easy popularization, non-invasive, quick, economical, bedside operation and no radiation. In recent years, the clinical application of ultrasonography in the diagnosis of pulmonary embolism has been gradually paid attention to. This article reviews the application progress of various ultrasonography in the diagnosis of pulmonary embolism.

In recent years, the U.S. Food and Drug Administration has approved two programmed death-1 (PD-1) monoclonal antibodies for the treatment of human cancer^[1]。 PD-1 antibody has gained widespread attention and recognition in the treatment of human cancer by blocking the PD-1/PD-L1 signaling pathway, reducing immune cell apoptosis and enhancing immune cell function, but its role in infectious diseases is still unclear. The research progress of PD-1 antibody in infectious diseases is summarized as follows.

Chronic obstructive pulmonary disease (COPD) is a common chronic disease of respiratory system, with high mortality and mortality rate and heavy socio-economic burden. It is an important public health problem in the world^[1,2]。 It is expected that COPD will be the third leading cause of death and the fifth largest disease burden in the world by 2020^[3]。 COPD is usually associated with cardiovascular disease, gastroesophageal reflux disease, osteoporosis and depression^[4,5,6]Disease co-existence, when COPD co-exists in an individual with one or more diseases^[7], known as COPD, with an incidence of 90% to 98%^{[4,8,9,10,11]}This imposes an additional burden on the health and economy of patients. Effective evaluation of COPD can help clinical medical staff to understand the severity of patients' disease, and provide a basis for formulating the best treatment plan and nursing measures. This article reviews the evaluation tools of COPD and their clinical value, in order to provide reference for clinical work.