2018年 · 第98卷第48期

Chronic obstructive pulmonary disease (COPD) is still a major chronic non-communicable disease worldwide, and its high incidence and disability rate seriously affect people's health. In November 2018, COPD Global Initiative systematically summarized the research progress in the field of COPD based on the important literature published in recent years, and released the 2019 edition of COPD Global Initiative Report, which updated many aspects involving COPD risk factors, early screening and diagnosis, active prevention, management of stable phase and acute exacerbation phase, etc.^[1]The main points of its update are now interpreted as follows.

Malignant tumors are a large class of diseases that threaten human health. The advent of immune checkpoint inhibitors (ICI) such as antibodies against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) has opened a new chapter in tumor treatment. Although ICI significantly improved the overall survival of some patients, clinical results showed that in the vast majority of unselected solid tumors, the objective effective rate of patients receiving ICI monotherapy was only 10% to 30%, and most patients could not benefit from it, that is, primary drug resistance; Even patients with effective treatment develop disease progression, i.e., secondary drug resistance, after a period of treatment. Researchers have conducted many in-depth studies on ICI efficacy predictors, drug resistance mechanisms and countermeasures. This article reviews the efficacy predictors, primary and secondary drug resistance mechanisms and countermeasures explored in clinical and scientific research of tumor ICI treatment. Research progress, in order to provide scientific basis and clinical guidance for ICI tumor treatment.

Example 1: A 32-year-old female was admitted to the hospital in December and May 2016 due to failure of inferior vena cava filter removal twice. The patient developed deep vein thrombosis (DVT) of the right lower extremity during pregnancy in January 2016 and a retrievable inferior vena cava (IVC) filter was placed at the local hospital. Endovascular filter removal was performed at a local hospital 3 months after filter placement, and the operation failed. The patient was then transferred to the Department of Vascular Surgery of our hospital, and the filter was removed with an endovascular gooseneck catcher, which was still unsuccessful. Abdominal CT showed that the filter was tilted, and part of the filter foot penetrated the vena cava wall (FIG. 1A)。 Considering that the patient is still young, lifetime anticoagulation is required if the filter is not removed, and multiple filter feet have penetrated the vena cava wall, one of which may damage the aorta (FIG. 1A), decided to perform laparoscopic filter removal. Diagnosis: (1) After placement of inferior vena cava retrievable filter; (2) Deep vein thrombosis of lower limbs. The patient underwent laparoscopic filter removal on December 7, 2016. Using general anesthesia, a 10, 10, 10, 5, and 5 mm cannula (Trocar) was placed in the umbilicus, midpoint of the umbilical and xiphoid process, midpoint of the umbilical and pubic symphysis, 5 cm to the right of the umbilicus, and under the xiphoid process, and the laparoscopic instrument was placed. The peritoneum was incised on the lateral side of the right paracolonic sulcus, the ascending colon and duodenum were pushed towards the midline, the kidney, renal vein and inferior vena cava were exposed, and the inferior vena cava was freed up to the tip of the filter and down to the tail of the filter. The ovarian vein and lumbar vein were clipped and severed with hemlok. The vascular occlusion band passes through the inferior vena cava and is placed at the tip and tail ends of the filter. A drainage tube about 1.5 cm long, 20 F, was cut and the tourniquet passed through this drainage tube (for blocking). After notifying the anesthesiologist, the distal and proximal ends of the inferior vena cava were blocked in turn (FIG. 1B)。 At the tip of the IVC filter, a longitudinal incision of the inferior vena cava is about 3 cm long. Because the filter hook is embedded in the wall of the inferior vena cava, the filter hook is separated with scissors. Using a catcher, the filter hook is enclosed and retrieved into the filter sheath (Figure 1C)。 IVC was rinsed with heparin water to remove intracavitary blood clots and air bubbles. The IVC incision was continuously sutured with 5-0 Prolene thread, and the proximal and distal blocking bands of the IVC were sequentially released. The operation time was 330 min, the bleeding was about 500 ml, and 4 units of suspended red blood cells were transfused. Postoperatively, low molecular weight heparin (Qizheng) was injected subcutaneously at 0.4 ml/12 h for 1 week. Hospitalized for 14 d, the patient was discharged in good condition.

A 43-year-old female was admitted to the Department of Infectious Diseases of West China Hospital of Sichuan University due to "low back pain for more than 5 months and intermittent fever for 1 month". In January 2014, the patient suffered from sudden low back pain during sleep at night, which was needle-like pain with paroxysmal attack. The pain was relieved when lying prone, and the pain was repeated, gradually appearing pain in the buttocks, posterior thighs, and lateral calves, accompanied by weakness in both lower limbs. In March, he developed weakness of both lower limbs, difficulty in standing and walking, and in April, he developed fever, with a body temperature of 40.2℃, accompanied by chills, chills, sweating, and headache. Previously, forehead pain was the main one, with an attack once a day, showing irregular fever, and at the same time, low back pain was aggravated, which was persistent, accompanied by pain and weakness in both lower limbs, and the patient could not sit up. In May, I went to a tertiary hospital, and many blood cultures were negative. Lumbar MRI showed edema of bone marrow in T11~ L5 vertebral bodies, uneven increase of intervertebral disc signal in L4~ L5, swelling of soft tissue in lumbar back, and a little fluid accumulation in the presacral space (Figure 1)。 Treated with carbapenem and vancomycin, his symptoms continued to worsen, and he was transferred to the emergency department of West China Hospital on 13 May 2014. Blood routine: Hemoglobin 90 g/L, platelet count 688×10⁹/L, white blood cell count 26.33×10⁹/L, the percentage of neutral rod-shaped nucleus granulocytes was 15.0%, and the percentage of neutral lobulated nucleus granulocytes was 70%. The erythrocyte sedimentation rate was 117 mm/h. Hepatic enzymology was normal, albumin 30.0 g/L, globulin 49.0 g/L, serum sodium 132.6 mmol/L, serum potassium 2.81 mmol/L. High sensitivity C-reactive protein 125 mg/L, procalcitonin 0.10 μ g/L, coagulation routine showed no abnormality, hepatitis B surface antibody and core antibody were positive, human immunodeficiency virus (HIV) antibody, hepatitis C antibody and syphilis antibody were negative, and cardiac color ultrasound showed no abnormality. Considering lumbar spine infection and pulmonary infection, the emergency department successively administered piperacillin/tazobactam for 7 days, moxifloxacin for 11 days + vancomycin for 7 days, and intermittently administered methylprednisolone 40 mg/d ×2 days. The patient's symptoms did not improve and he was admitted to the hospital on May 26. Past history, family history and personal history are not special. Physical examination at admission: body temperature 37 ℃, pulse 95 beats/min, breathing 20 beats/min, blood pressure 145/95 mmHg (1 mmHg =0.133 kPa). There were no abnormal signs in the heart, lung and abdomen, and the skin temperature of the bilateral lower back was slightly higher and tenderness was obvious; Lumbar spinous process tenderness and percussion pain were obvious, bilateral hypoesthesia below the inguinal area was reduced, and the muscle tone of both lower limbs was reduced. The muscle strength of the lower limbs was 2~3 in the proximal end and 4 in the distal end, mainly with weakening of knee extension and ankle dorsal extension and thumb dorsal extension. Both pathological signs and meningeal irritation signs were negative.

A 36-year-old male was admitted to the hospital on 3 February 2016 due to persistent fever for 4 days and cough and sputum for 1 day. The patient developed high fever after catching a cold 4 days ago, up to 40℃, accompanied by chills, dizziness, fatigue, muscle soreness, without cough, expectoration, nausea, vomiting, chest tightness, chest pain and chills; Accompanied by diarrhea, yellow non-shaped stools, without abdominal pain. The patient's body temperature can be temporarily lowered after taking "antipyretic drugs", but it cannot be lowered to normal. One day ago, the patient was given azithromycin intravenously and cefprozil capsules orally in another hospital. The temperature did not drop and went to the emergency department of Shengjing Hospital. Moxifloxacin was given intravenous drip. The patient had a cough and yellow sticky sputum, so he was admitted to hospital. The patient had no previous history of chronic diseases and no history of infectious diseases. Drink alcohol for 10 years and deny smoking history.

A 16-year-old male was admitted to the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University on March 30, 2018 because "physical examination found that the abdominal cavity occupied 5 days". The patient was admitted to the local hospital 5 days ago due to postprandial abdominal pain, considering gastroenteritis, and was hospitalized. During this period, both abdominal color ultrasound and abdominal CT showed that the abdominal cavity occupied space. For further treatment, he came to our hospital on March 30, 2018. Has a history of allergic asthma for 2 years and improved after treatment; Has a history of chronic diarrhea for more than 1 year, and has not been systematically examined and treated. Infectious diseases, drug and food allergies, surgical trauma, blood transfusions and family history were denied. The initial diagnosis was retroperitoneal mass occupation.

Thrombotic microangiopathy (TMA) is a group of acute clinicopathological syndromes characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and ischemic organ involvement caused by various causes. Its pathological and clinical manifestations are similar, but the pathogenesis is diverse. The disease spectrum involves professional fields such as kidney disease, rheumatism, hematology, obstetrics and tumor, and the diagnosis and treatment are complicated. In recent years, with the continuous deepening of research on the pathogenesis of TMA, its diagnosis and treatment plan has made a great breakthrough, but there are still doubts. This article aims to summarize the research progress of TMA from the perspective of clinical practice, with emphasis on atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP).

With the development of biomedical research technology, new diagnosis and treatment methods are constantly emerging, and these questions should be studied and the technology to be developed should not be developed. For example, in genetic testing, embryonic stem cell research, AIDS research and organ transplantation research, there are problems of respect and protection of human dignity, interests and rights. Given the importance of ethics, ethical issues are unavoidable problems for researchers in medical research.