2018年 · 第41卷第05期

It is early summer, and the summer is gradually growing. With the enthusiasm of summer, the 5th issue of this magazine in 2018 meets you readers!

For a long time, there has been a deep-rooted prejudice in academic circles, that is, only SCI is the first and only SCI is proud. If a paper is published in a Chinese journal or a journal not included in SCI, it may be regarded as having no value or even a real "paper". This kind of absurdity, which is harmful to the healthy development of academics, has come to the moment of complete transformation!

The concept of real-world research has been put forward for nearly 50 years, and it has become a hot word in clinical research. However, there are still many misunderstandings about the definition, advantages and disadvantages of real-world research and its application. This paper combs and explains related concepts and key contents to help readers understand and apply real-world research comprehensively and correctly.

acute pulmonary embolism (APE) is a common and serious disease. The literature reports that the mortality rate is about 11% within 2 weeks of diagnosis^[1]If the thrombus persists within 3 months after diagnosis, the mortality rate can reach more than 15%^[1]。 The results of survey on the incidence, diagnosis and treatment of APE in China show that the diagnosis rate of APE has increased by 10~30 times in recent years^[2]。 At present, CT pulmonary angiography (CTPA) is the first noninvasive method for the diagnosis of APE^[3,4,5,6]。 With the continuous progress of CT equipment and technology, the sensitivity and specificity of pulmonary embolism detection have been significantly improved compared with the past^[3,4,5,6]However, there are still difficulties and challenges in clinical diagnosis of pulmonary embolism. The reasons include: (1) the number of images is huge, and the diagnosis is time-consuming; (2) Looking for low-density thrombus in high-density contrast agent will cause visual fatigue in human eyes; (3) Imaging beginners may miss the diagnosis because of inappropriate window width and/or window position. There is no objective quantitative method to evaluate the severity of pulmonary embolism. Therefore, we need a technology and method that can automatically read, quickly detect and accurately quantify to improve the diagnosis level of pulmonary embolism. Based on computer-aided detection technology, this study discussed the application value of computer-aided detected (CAD) in APE patients.

The main pathological features of pulmonary fibrosis are persistent alveolar epithelial cell damage, abnormal proliferation of fibroblasts/myofibroblasts and excessive secretion of extracellular matrix (ECM) leading to the destruction of normal lung structures and eventually the formation of pulmonary fibrosis. It has high incidence, unclear pathogenesis, lack of effective treatment and poor clinical prognosis. Studies have shown that oxidative stress is closely related to pulmonary fibrosis. Daniil et al.^[1]Increased lipid peroxide production was found in lung tissue of patients with pulmonary fibrosis, and the severity was positively correlated with oxidative stress levels.

Case 1: A 56-year-old male was admitted to the hospital on November 7, 2011 mainly due to "intermittent cough, expectoration, and blood in the sputum for 5 months, aggravated for 10 days". The patient coughed intermittently and sputum with blood in the sputum for 5 months. When the cough was severe, he felt bilateral chest pain, without fever, night sweats and dyspnea. Hemoptysis was performed twice daily for 10 days prior to admission, with a total of about 30 ml. CT of the chest in the external hospital (October 23, 2011) showed a tumor at the opening of the left main bronchus. Under the bronchoscope (October 25, 2011), a cauliflower-like tumor on the left side of the carina was seen, with a small amount of bleeding on the surface. No cancer cells were found in the microscopic brush. The biopsy pathology was chronic inflammation of the tracheal mucosa, partial epithelial squamous metaplasia, and mild atypical hyperplasia. He has a history of smoking for more than 30 years, and his smoking index is 30 packages per year. Physical examination: body temperature 36.2℃, pulse rate 76 beats/min, respiratory rate 20 beats/min, blood pressure 118/80 mmHg (1 mmHg =0.133 kPa), clear consciousness, no superficial lymph node enlargement, shortness of breath score 4 points, clear breathing sounds in both lungs, no dry and wet rales, and no abnormalities. After admission, on November 8, 2011, chest CT examination showed that the carina was widened, and the carina was deviated from the left side with high density shadow, which was significantly enhanced after enhanced scan (Figure 1), on November 9, 2011, bronchoscopy showed nodular growth of the tumor at the carina (Figure 2), the left main bronchus was narrowed by about 50%, so the tumor was removed with a snare under a hard scope, and most of the tumor was eliminated (Figure 3)。 The postoperative shortness of breath score was 0. The postoperative pathological report was glomus tumor. Because the lesion was located at the carina, which could not be operated, and because the carina was widened, there was still a residual mass after the tumor was removed. On November 29, 2011, the lesion was implanted at the carina under bronchoscope¹²⁵10 iodine particles. On the second day after operation, the chest CT reexamination showed good particle distribution and position (Figure 4), the patient's symptoms improved and he was discharged. Bronchoscopy six months after operation showed no tumor recurrence at the original surgical site (Figure 5), reexamination of chest CT 2 years after surgery showed that the subcarina lesions were smaller than before (Figure 6), was followed up for 6 years, and the lesions were stable.

The female patient was admitted to the hospital on February 26, 2017 due to "cough for more than 2 months". Two months ago, the patient developed cough and fever after catching a cold, with a maximum body temperature of 37.8℃, cough a small amount of white sticky sputum, no discomfort such as chest pain, hemoptysis, dysphagia and dyspnea, and the cough symptoms did not improve significantly after taking cold medicine (details unknown) by himself, so he went to the local hospital on February 22, 2017. Chest enhanced CT showed that the left upper mediastinum and paratracheal space were occupied, and the lesions were not significantly enhanced, so "lymphangioma or lymphoma" was considered. Now the patient is admitted to our hospital for further diagnosis and treatment. He complained that he had chest tightness and shortness of breath after occasional activities, but he had no other obvious discomfort.

A 33-year-old female was admitted to the hospital on 26 July 2017 due to "right chest pain for 15 h". The patient suddenly fainted once during exercise on July 25, 2017, and woke up on his own after about 5 s, accompanied by right chest pain, which was strip-shaped and appeared during deep breathing. There was no cough, chest tightness, fever, hemoptysis, abdominal pain, headache, hematemesis and melena. The last menstrual period was July 12, 2017. Routine blood test in the emergency room of our hospital showed hemoglobin 114 g/L, white blood cells, platelets, myocardial enzymes, myocardial troponin, D-dimer, glutamate aminotransferase, blood sodium, blood chloride, blood glucose, electrocardiogram and upper abdominal CT showed no obvious abnormalities, and blood potassium was 3.4 mmol/L. Chest CT scan showed nodular high-density shadows in the middle lobe of the right lung, about 2.25 cm ×2.16 cm ×2.10 cm, thickened blood-supplying pulmonary artery entering the nodule, multiple patchy flocculant high-density shadows in the right lung, right pleural effusion, and partial incomplete expansion of the lower lobe of the right lung (Figure 1,Figure 2,Figure 3)。 Given anti-infective treatment, the patient's chest pain was relieved, there was no chest tightness and dizziness at rest, the blood pressure was 85-90/44-60 mmHg (1 mmHg =0.133 kPa), and the heart rate was 88 beats/min. Physical examination at admission: body temperature 37.1 ℃, pulse rate 80 beats/min, respiratory rate 20 beats/min, blood pressure 90/60 mmHg, percutaneous oxygen saturation 96% (without oxygen). Conscious, autonomous position, no damp and cold skin, unpalpable swelling of superficial lymph nodes, no dilatation of superficial capillaries, centered trachea, slightly full right thorax, weakened right speech tremor, voiced sound at percussion below right 8th posterior rib, weakened breathing sound in right lower lung, no dry and wet rales, heart rate 80 beats/min, homogeneous rhythm. There was no edema in both lower limbs. The CT film of the chest showed that the CT value of right pleural effusion was high and uneven [(20±5) HU]. The patient's basal blood pressure was 120/70 mmHg at ordinary times. Combined with the history of syncope, the possibility of hemothorax could not be ruled out. After hospitalization, the coagulation function was found to be normal. After bedside B-ultrasound positioning, thoracocentesis was performed. Bloody pleural effusion was extracted during local anesthesia without coagulation. Bloody pleural effusion was extracted at two different puncture sites. Hemothorax was considered. The patient had dizziness and syncope symptoms during the third puncture, and immediately stopped the operation. After lying down, he woke up. After lying down, his blood pressure was measured to be 89/53 mmHg. After lying down, he was given normal saline to expand his volume. He immediately consulted the thoracic surgery department.

Rifampicin (RIF) resistance real-time fluorescence quantitative nucleic acid amplification (GeneXpert MTB/RIF) is a semi-nested fluorescence quantitative PCR in vitro molecular diagnostic technology based on nucleic acid amplification^[1]Simple operation, high sensitivity and specificity, recommended for rapid diagnosis of tuberculosis by the World Health Organization (WHO) in 2010^[2]。 Although GeneXpert MTB/RIF is simple to operate, and only one step requires manual operation during specimen predigestion, and the test results are reported after 2 hours, abnormal results such as "error", "invalid" and "no result" due to human error or sample quality problems occur from time to time during the operation. In the laboratory examination of TB prevention and control institutions at the district and county level, the frequency of the above abnormal results can reach more than 10%^[3]This leads to waste of clinical specimens and test kits, and delays the diagnosis and treatment of patients. Given that the specimens tested by the GeneXpert MTB/RIF technique are directly from patients, and some specimens are obtained after invasive examination, repeated sampling is difficult, so reliable test results are important. This study intends to retrospectively analyze the common abnormal causes in 1 486 GeneXpertMTB/RIF test results in our hospital from September 2016 to July 2017, so as to reduce the occurrence of abnormal test results such as "error" and "invalidity".

A 69-year-old male was admitted to the hospital on October 11, 2016 mainly due to "left chest pain and fever for 1 week". The patient developed fever without trigger 1 week ago, with the highest body temperature of 39 ℃, accompanied by dull pain in the left chest, the symptoms persisted and gradually worsened, accompanied by cough, cough of yellow phlegm, denial of hemoptysis and other discomfort. After admission, blood routine showed a white blood cell count of 47.4×10⁹/L, the proportion of neutrophils was 91.8%; High sensitivity C-reactive protein was 292 mg/L. Routine examination of pleural effusion showed that the total number of nucleated cells was 5 560/ml, with mononuclear cells accounting for 0.12 and multinuclear cells accounting for 0.88; Pleural effusion biochemistry showed that total protein was 42.0 g/L, lactate dehydrogenase was 901 IU/L, glucose was 0.42 mmol/L, and adenosine deaminase was 21.7 U/L (blood biochemistry showed that total protein was 66.8 g/L, lactate dehydrogenase was 105 IU/L, and blood glucose was 5.33 mmol/L on that day); Pleural effusion pH was 6.788. Pleural effusion and blood tumor markers, pleural effusion and blood culture were not found to be abnormal. Chest CT enhancement revealed massive left pleural effusion, partially encapsulated, with left lung compression atelectasis (Figure 1)。 Intravenous drip of levofloxacin, meropenem, cefoperazone/sulbactam and norvancomycin were given successively, and thoracic drainage was simultaneously placed. The peak body temperature fluctuated from 37.5 to 38.5 ℃ due to the encapsulation of pleural effusion with large amount of separation and poor drainage. Therefore, medical flexible thoracoscope (Olympus Company, Japan, model LTF-240) combined with rigid thoracoscope (Storz Company, Germany) under local anesthesia was treated. First, the thoracic cavity was comprehensively observed with a flexible thoracoscope. It was found that the lung tissue, visceral pleura and parietal pleura were seriously thickened and adhered, with a large number of white cellulosic necrosis attached to the surface, and a large number of yellow filthy and turbid pleural effusion separated. The flexible thoracoscopic biopsy forceps attempt to bluntly separate the adhesive tape, but the initial separation efficiency is low because the biopsy forceps are small, insufficiently rigid, and the adhesive tape is flexible and complex in structure. Therefore, the original approach was replaced with a rigid thoracoscope and matching cannula, and the rigid thoracoscope biopsy forceps were used to continue the blunt separation of adhesive bands and parietal pleura, which significantly improved the separation efficiency. Finally, the remaining part is adhered, or the angle is too large, or the risk of injury to adjacent important organs is high, and it is replaced with a flexible thoracoscope with better flexibility for operation again (see the operation video for details,Figure 2)。 After separation, the thoracic space was significantly enlarged, and the pleural effusion was fully absorbed, and the chest tube was placed in the drainage bottle. On the second day after operation, the patient's body temperature returned to normal and the chest pain was completely relieved. Blood routine reexamination showed white blood cell count 8.3 10⁹/L, the neutrophil ratio was 70.0%; The high-sensitivity C-reactive protein was 67.62 mg/L. Re-examination of chest X-ray showed obvious recruitment of left lung and obvious reduction of pleural effusion (Figure 3，Figure 4)。 The patient was discharged smoothly after removing the chest tube and changing antibiotics to oral administration. After 10 months (August 2017), the patient was followed up by telephone. The patient did not have any symptoms such as obvious fever and chest pain, and did not see a doctor further.

"A case of microscopic polyangiitis with bronchiectasis" written by Zhang Hongying and others was published in the case report column of Volume 41, Issue 1, 2018, and an editor's note was distributed at the same time^[1]It can be seen that the editorial department feels that this article is controversial. After reading this article repeatedly, the author first felt that there was enlightenment and benefit after reading it, but I disagree with the author's conclusion that this patient's bronchiectasis for 10 years was caused by microscopic polyangiitis (PMA), in other words, PMA can show bronchiectasis.

idiopathic pulmonary fibrosis (IPF) is a special type of unexplained, chronic progressive interstitial lung disease (ILD) that occurs in adults. Imaging and/or histology are consistent with usual interstitial pneumonia (UIP), which occurs in the elderly. At present, there is a lack of effective treatment drugs, and the average survival time is only 2.5 to 3.5 years^[1]。 Individual survival of IPF patients varies greatly. The disease can progress slowly and survive for many years, or acute exacerbation can lead to rapid deterioration of lung function and death in a short time^[2]。 For IPF, a disease with high mortality and poor prognosis, it is very important to evaluate the severity of patients' disease effectively. There is an urgent need for clinical staging methods that can objectively and comprehensively evaluate the severity of IPF, which can be used for disease assessment, prognosis analysis, treatment guidance, etc^[3]。 We reviewed domestic and foreign literatures for nearly 50 years (January 1970 to January 2018) through databases such as PubMed, SCOPUS and Web Of Science, and summarized the current research progress Of IPF severity staging as follows.

Exercise training is the cornerstone of comprehensive pulmonary rehabilitation program. It is not only the best way to improve muscle function and exercise endurance of patients with chronic obstructive pulmonary disease (COPD), but also can indirectly relieve exertion dyspnea, reduce emotional disorders, and improve cardiovascular function^[1]。 COPD is often associated with other diseases, including cardiovascular disease, malnutrition, osteoporosis, anxiety and depression, and metabolic syndrome, etc. Comorbidities will further reduce the patient's exercise ability, which is a key predictor of mortality in COPD patients^[2,3]。 The limitation of COPD exercise may be related to pulmonary ventilation dysfunction, pulmonary ventilation dysfunction, peripheral muscle dysfunction, respiratory muscle dysfunction, cardiac insufficiency or many of the above dysfunctions. Compared with healthy adults of the same age, the reasons why COPD patients are reluctant to exercise mainly include: lack of infrastructure, weak willpower and social impact. The general principle of COPD exercise training is consistent with that of healthy people, but patients with COPD need professional therapists to evaluate their exercise ability through cardiopulmonary exercise test before exercise training to formulate individualized exercise prescription, and help to rule out related cardiovascular diseases to ensure the safety of intervention measures. Cardiopulmonary exercise test can help to reveal some hidden exercise-related problems, such as hypoxemia, arrhythmia, myocardial ischemia and musculoskeletal problems to some extent^[4]。 In order to improve aerobic exercise capacity and strengthen muscle strength, the total exercise load must exceed the daily load. When the patient's aerobic exercise capacity and muscle strength are improved, the total exercise load must be continuously strengthened. In order to maximize the effect of sports training, it is necessary to combine multiple training modes. The choice of exercise training mode depends on the patient's own physiological needs, training purpose and available rehabilitation equipment.

inhaled corticosteroid (ICS) is an important component in the treatment of bronchial asthma (asthma) and chronic obstructive pulmonary disease (COPD). Recent literature reports that long-term use of ICS is associated with an increased risk of lung infection, and concerns about ICS have also arisen. With the accumulation of research evidence, the evaluation of this risk is gradually objective and comprehensive. The relevant research progress is summarized as follows.

Early life events (such as natural infection, microbial exposure or allergen exposure) significantly affect the development of allergic diseases in adulthood, including bronchial asthma (asthma)^[1]。 Children have been reported to be protected from asthma if they grow in an environment that exposes them to a wide range of microorganisms, such as traditional farms^[2,3]。 This is consistent with the "hygiene hypothesis" put forward by Strachan in 1989, which believes that the body's immune system is not mature in the early stage of life, and the Th2 response is dominant. The natural contact or infection of microorganisms such as viruses or bacteria induces the production of Th1 cytokines such as interferon-γ and transforming growth factor (TGF) -β, which tilts the immune response to Th1 type. However, the hygienic living environment weakens the microbial stimulation and cannot stimulate the Th1 response that can compete with Th2 response, thus leading to the occurrence of allergic diseases. It is undeniable that the hygiene hypothesis provides important support for the study of asthma, but the latest research results do not seem to support the hygiene hypothesis. Children in some western countries^[4]and adults^[5]Asthma prevalence is beginning to show a downward trend, but there is no evidence of a decrease in health in these countries. Asthma is a complex disease, and the interaction between the time of exposure, the type of exposure and the genetic susceptibility of the body affects the occurrence and immune response of asthma.

A 79-year-old male was admitted to the hospital on April 16, 2016 due to "upper abdominal pain and low back pain for more than 2 months, cough and wheezing for 2 days". The patient developed upper abdominal pain and low back pain without trigger 2 months ago, which were persistent, without headache, nausea, vomiting, fever, chest pain, hemoptysis, numbness of limbs and mobility impairment. 2 d ago, cough, cough a small amount of white phlegm, and sustain wheezing after activity. Physical examination: clear consciousness, unpalpable swelling of superficial lymph nodes. After auscultation, the respiratory sounds of both lungs were thick, and dry rales could be heard. Soft abdomen, tenderness in the upper abdomen, no rebound pain, unpalpable liver and spleen under the costs. Auxiliary examination: Blood routine showed that white blood cells were 12.5×10⁹/L, neutrophils were 0.77, and ESR was 19 mm/1 h. Serum lactate dehydrogenase (LDH) was 1 697 U/L (normal reference value: 114-240 U/L), and the G test was normal. Serum tumor marker carcinoembryonic antigen (CEA) was 7.26 μ g/L (normal reference value: 0-3.4 μ g/L), neuron-specific enolase (NSE) was 141 μ g/L (normal reference value: 0-15.2 μ g/L), and cytokeratin 19 fragment (CYFRA211) was 44.64 μ g/L (normal reference value: 0-3.3 μ g/L); Carbohydrate antigen 199, prostate specific antigen and alpha-fetoprotein were all normal. The sputum culture was negative, and no acid-fast bacilli were found in the sputum smear. Color ultrasound of the neck showed that several hypoechoes of different sizes could be seen in the right supraclavicular area, with clear boundaries, the larger one was 2.2 cm ×1.5 cm; Hypoechoic 2.1 cm ×1.1 cm can be seen in the left supraclavicular area, with clear boundary; Bilateral supraclavicular enlarged lymph nodes were considered, and no mass was seen. Abdominal color Doppler ultrasound showed multiple cystic solid mass occupation in the liver, and hypoechoic mass occupation in the right lobe of the liver with the formation of internal nourishing artery; Prostatic hyperplasia, bladder diverticulum, bladder spinalization, mild hydrops in both kidneys. Chest CT showed multiple cysts and cavities in both lungs (Figure 1,Figure 2,Figure 3,Figure 4)； Nodular foci in the mediastinum and both hilar areas, considered as enlarged lymph nodes (Figure 5)； Some thoracic vertebral body density increased unevenly. Abdominal CT showed multiple low-density foci in the liver (Figure 6)。 There were no abnormalities in brain CT. CT of the thoracic spine showed a compression fracture of the T12 vertebral body with involvement of the spinal canal. CT-guided percutaneous liver and right lung biopsy was performed, 2 tissues were extracted from the liver, and 20 ml of bloody liquid was extracted from the liver, which appeared bloody and turbid, with 5-10 white blood cells/HP; LDH was 4,999.0 U/L, adenosine deaminase>300.0 U/L, CEA was 14.0 μ g/L, CYFRA211>500.0 μ g/L, and NSE>370.0 μ g/L. No acid-fast bacilli and tumor cells were found in liver puncture fluid. Immunohistochemical staining results of lung biopsy: TTF-1 (-), CK7 (-), CK5/6 (+), P63 (+), CgA (-), Syn (-), Ki67 (+) 60%; Immunohistochemical staining results of liver biopsy: TTF-1 (-), CK7 (-), CK5/6 (+), P63 (+), CgA (-), Syn (-). The final diagnosis was poorly differentiated squamous cell carcinoma of the lung with liver metastasis (Figure 7，Figure 8)。 During hospitalization, anti-infection, anti-asthma, expectorant and other treatments were given. The patient's upper abdominal pain and low back pain gradually worsened, with weakness in both lower limbs and hypoesthesia below the xiphoid process. He was discharged automatically and died one month later.

A 39-year-old male was admitted to Xiangya Hospital of Central South University on May 15, 2015 due to "repeated cough, cough of purulent sputum with hemoptysis for 14 years, and recurrence and aggravation for 1 month". Fourteen years ago, the patient had cough and expectoration, accompanied by hemoptysis due to cold. He went to the local hospital for treatment (details unknown), and the symptoms of cough and hemoptysis improved. After that, he occasionally had cough and expectoration, with blood in the sputum. The local hospital gave anti-infective treatment (specific medication unknown), and the symptoms of cough and expectoration improved. One month ago, he had cough and purulent sputum again due to cold, accompanied by chest pain, shortness of breath, and dyspnea after activity, so he went to a local hospital. CT examination in the local hospital showed left lung lesions. Considering the possibility of tuberculosis combined with Aspergillus infection, he was given anti-tuberculosis treatment and anti-infection treatment for 2 weeks, and the patient's clinical symptoms were relieved compared with before. I lost more than 10 pounds in the past month. Previously healthy, the patient had coughed up hair-like filaments. Physical examination at admission: body temperature was 36.7 ℃, pulse rate was 80 beats/min, respiratory rate was 20 beats/min, and blood pressure was 114/64 mmHg (1 mmHg =0.133 kPa). Chronic disease, coarse breathing sounds in both lungs, and a little wet rales can be heard in the left lung. Laboratory tests after admission: ESR was 50.00 mm/1 h, galactomannan test (GM test) and 3-β-D glucan test (G test) were normal, tuberculosis antibodies IgM and IgG were negative, blood routine, carcinoembryonic antigen, full quantification of procalcitonin and alpha-fetoprotein were normal. On May 16, 2015, our hospital chest CT plain scan + enhancement: the left upper lung bronchus showed cystic dilatation, and a large cavity was visible. Several mixed density masses and nodules were visible in the cavity, partially fused, and fat density (-72 HU), punctate calcification (98 HU) and parenchymal density (56 HU) were visible in it, and enhancement (76 HU) was visible in the solid part after enhancement (Figure 1,Figure 2,Figure 3), bronchiectasis of the left lower lung, patch shadows can be seen around it, and pulmonary aspergillosis is considered for CT diagnosis. Bronchoscopy: A prominent mass was seen in the bronchial lumen of the anterior branch of the left upper lobe, with a large amount of straw-like and stone-like substances (Figure 4)。 Bronchial lavage was negative for acid-fast staining, fungal culture negative, and bacterial culture Enterobacter cloacae. Pathological report of bronchoscopy: (anterior branch of left upper lobe) a small amount of mucosal suppurative inflammation, squamous epithelial cell hyperplasia and metaplasia, and a small amount of inflammatory exudate. Negative for PAS staining and negative for acid-fast staining. After completing the relevant examinations, the admission diagnosis considered the possibility of fungal infection, and the left pneumonectomy was performed on June 1, 2015. Intraoperative findings: partial thoracic atresia, extensive pleural adhesion, no pleural effusion, mass located in the left upper lung, about 5 cm ×6 cm, with hair inside, cavity lesions in the left lower lung and bronchiectasis (Figure 5)。 Pathological diagnosis: Left whole lung bronchiectasis and mature cystic teratoma (Figure 6) (nodular mass, 5 cm ×4 cm ×3 cm), and no tumor was seen on the bronchial stump. Regular postoperative review showed no obvious recurrence.

The patient was a 68-year-old male. He was admitted to hospital on July 12, 2016 due to "intermittent chest tightness and shortness of breath for 2 months". The patient developed chest tightness and shortness of breath during activity 2 months ago, accompanied by sweating, without fever and chest pain. The patient developed mild edema of the lower extremities 1 month ago and urine routine showed urine protein (+). CT of the chest in the external hospital showed multiple amural and thin-walled cystic changes in bilateral lung fields, and right pleural cavity and pericardial effusion. Multiple enlarged lymph nodes in the mediastinum and both hilum, partially fused. For further diagnosis and treatment, he was admitted to our hospital. The patient lost 5 kg in the last 5 months. Previous history of tuberculous pleurisy, left clavicle fracture fixation after trauma 10 years ago. 20 years of smoking, 20 cigarettes/d. Physical examination: body temperature 36.5 ℃, pulse rate 73 beats/min, respiratory rate 22 beats/min, blood pressure 124/76 mmHg (1 mmHg =0.133 kPa). There were no yellow stains and bleeding spots on the skin and mucosa, and no palpable swelling of the superficial lymph nodes. There was no abnormality in the head and neck, no deformity in the thorax, weakened tactile speech tremor in the right chest, voiced sound in the right lower lung knocking, weakened respiratory sound in the right lower lung, and no pleural friction sound was heard on both sides. Heart rhythm, no murmur. The abdomen was flat and soft, without tenderness, and the liver and spleen were not palpable under the costs. No pestle fingers, mild concave edema of both lower limbs.

The animal model has a single genetic background, controllable conditions and good experimental repeatability. It is easier to establish the direct relationship between disease progression and sample composition changes^[1]。 Standardization and standardization of the collection and storage of biological samples from model animals is critical. The chronic obstructive pulmonary disease and pulmonary vascular disease team of Guangzhou Institute of Respiratory Diseases has rich experience in establishing animal models, and has formed its own norms and characteristics in the establishment of clinical biological sample resource bank^[2,3]。 Based on our experience and lessons in the establishment of resource bank and animal model, the methods of collecting and storing rat biological samples are briefly described in this paper.

Pulmonary hypertension is a kind of malignant pulmonary vascular disease characterized by progressive increase of pulmonary vascular resistance, which can lead to right heart failure or even death if it continues to develop^[1]。 In 2015, the European Society of Cardiology/European Society of Respiratory Diseases (ESC/ERS) jointly released the latest edition of the "Guidelines for the Diagnosis and Treatment of pulmonary hypertension". pulmonary hypertension refers to the mean pulmonary arterial hypertension (mPAP) ≥25 mmHg (1 mmHg =0.133 kPa) measured by right cardiac catheter at rest^[2,3]。 Continuously increasing pulmonary vascular resistance will lead to increased afterload of the right ventricle, resulting in enlargement and vascular remodeling of the right ventricle and right atrium^[4,5,6,7]。 Electrophysiological findings suggest a decrease in the area of right atrial conductivity in patients with pulmonary hypertension, as well as an increase in the area of low or no voltage^[8]。 Therefore, various abnormal ECG manifestations may occur. The application value of ECG in pulmonary hypertension is introduced as follows.

Chronic obstructive pulmonary disease (COPD) is a common and frequently occurring disease, which seriously endangers people's health and affects the quality of life. At present, it is the fourth cause of death and the third disease burden in the world. The pathogenesis of COPD is complex, and it is related to the interaction of multiple gene variants and environmental factors. Smoking is the main risk factor of COPD. However, only 10% ~20% of heavy smokers have the disease. There are obvious individual differences in the response of different smokers to smoking. Genetic susceptibility plays an important role in the pathogenesis of COPD. The α 1-antitrypsin family (AAT) is a certain gene related to the pathogenesis of COPD. The AAT family includes SERPINA1 gene, SERPINE2 gene and SERPINA3 gene. At present, the results of whether the latter two genes are related to COPD are inconsistent, but the correlation between SERPINA1 and COPD is clear. However, most of the research results on these genes come from the Caucasian population, and the genetic susceptibility of COPD often has regional or ethnic differences. There are not many studies on SERPINA1 in China. This paper mainly explores the relationship between SERPINA1 and COPD and the relationship between smoking, lung function and COPD.

Nintedanib and pirfenidone are anti-fibrosis drugs in clinical use at this stage. Both of them can delay the progression of patients with idiopathic pulmonary fibrosis (IPF), and their anti-pulmonary fibrosis mechanisms are different. However, the number of studies on the safety and efficacy of the combination of the two in the treatment of IPF is limited. To this end, a clinical trial comparing nintedanib combined with pirfenidone and nintedanib alone in the treatment of IPF was conducted to clarify the differences in safety, clinical tolerability, pharmacokinetics and efficacy between the combination and monotherapy groups. Methods This study was a 12-week randomized, open-label clinical trial that screened IPF patients ≥40 years of age with FVC% ≥50% of the predicted value. After a 4-week washout period (during which patients received nintedanib 150 mg twice/d orally) and then randomized into 2 groups, the combination treatment group received nintedanib orally (150 mg twice/d) in combination with pirfenidone (267 mg three times/d; adjusted to 534 mg three times/d after 1 week; adjusted to 801 mg three times/d after 1 week for 10 weeks), the monotherapy group received nintedanib orally only (150 mg twice/d for 12 weeks). The primary endpoint was the incidence of gastrointestinal adverse reactions within 12 weeks of the treatment period; Secondary endpoints were pre-dose plasma concentrations of nintedanib (baseline, Week 2, Week 4), pre-dose plasma concentrations of pirfenidone (Week 2, Week 4). Results A total of 136 patients with IPF were screened, 111 cases were randomized, but 6 cases withdrew during the washout period. Finally, 105 cases were randomly divided into monotherapy group (52 cases) and combination group (53 cases). The incidence of gastrointestinal adverse events during treatment was 69.8% (37/53, combination group) and 52.9% (27/51, monotherapy group), respectively. Plasma concentrations of nintedanib did not differ between the two groups. The decrease in FVC between baseline and the end of the 12-week trial was 13.3%/17.4 ml (48 patients in the combination treatment group) and 40.9%/31.4 ml (44 patients in the monotherapy group), respectively. Conclusion the tolerability and safety of nintedanib combined with pirfenidone in the treatment of patients with IPF are similar to those in the monotherapy group. This study provides a basis for the development of combination therapy with antifibrotic drugs in IPF patients to further clarify the safety and efficacy of combination therapy. (This clinical study registration number is NCT02579603).