2015年 · 第95卷第46期

In recent years, targeted drugs such as epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have become one of the important treatments for advanced non-small cell lung cancer (NSCLC). In patients with advanced NSCLC with EGFR gene mutation, a series of international and domestic multicenter clinical studies have confirmed that EGFR targeted therapy can significantly reduce the risk of disease progression or death and improve the quality of life of patients. In lung cancer patients without EGFR gene mutation, clinical research evidence suggests that targeted drugs should not be used. These clinical studies and systematic analyses indicate that EGFR gene mutation detection is a prerequisite for the use of EGFR-TKIs in patients with advanced lung cancer.

Penicillium marneffei (PSM) is an invasive deep fungal disease caused by infection with Penicillium marneffei (PM)^[1]。 At present, the exact route of infection is still unknown, and it often causes disseminated infection in the whole body, even invades the main airway and bronchi, causing the destruction, collapse and obstruction of airway, resulting in fatal asphyxia^[2]。 Due to the rare reports of PM invasion of airway, routine imaging examination is difficult to detect, and diagnosis is difficult. Misdiagnosis and misdiagnosis often occur, and eventually serious complications occur. From January 2013 to June 2015, three patients with PM diagnosed and treated in the Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University were diagnosed with disseminated PSM with tracheal-bronchial-pulmonary involvement due to repeated lung shadow treatment. The etiological basis was finally obtained by fiberoptic bronchoscopy (fiberoptic bronchoscopy). Satisfactory results were achieved after aerosol inhalation and combined intravenous application of amphotericin B.

A 38-year-old female was admitted to the hospital on 28 April 2014 due to "intermittent upper abdominal discomfort for 2 years and abdominal mass found for 2 months". Two years ago, the patient experienced paroxysmal upper abdominal discomfort with abdominal pain and hiccups, which occurred 15 to 16 times a month. It appeared 10 to 15 minutes after eating, and relieved spontaneously after about 1 to 2 hours, without headache, palpitations and hyperhidrosis. He had a history of constipation for 2 years, and the patient was not diagnosed and treated. The patient had no abdominal pain, anorexia, nausea, vomiting, no melena and weight loss, no erythema migrans, no chest stiffness, shortness of breath, good spirit and appetite, dry stool for the past 4 to 5 years, and was given glycerol preparations to assist in defecation. On 9 March 2014, the tumor marker CA199 was 55.08 U/ml (normal<37.00 U/ml). Abdominal B-ultrasound: About 116 mm ×65 mm mixed echoes were seen in the right abdomen, with clear boundaries, and most of them were solid echoes, showing multiple anechoic areas. Abdominal CT: A mixed density mass shadow was seen in the abdominal cavity, about 96 mm ×66 mm in size, compressing the inferior vena cava, and the gastric wall in the gastric antrum was slightly thickened. Heterogeneous enhancement of the mass after enhancement. Consider abdominal space-occupying lesions, pancreatic space-occupying lesions, excluding stromal tumors (Figure 1)。 Admitted to the pancreatic group of basic surgery, and completed the relevant examinations: complete blood cell analysis: red blood cell count 4.15×10¹²/L, hemoglobin 99 g/L, hematocrit (HCT) 0.322. Urinary routine: 100 red blood cells/HP, gastroscopy: chronic superficial gastritis, external pressure bulge of descending duodenum (Figure 2)。 Helicobacter pylori (HP) negative (–). Endoscopic ultrasound: cystic mass of external pressure in the descending duodenum with normal pancreatic echo (Figure 3)。 Pancreatic thin scan enhanced CT: A massive soft tissue shadow, about 81 mm ×129 mm, was seen in the right upper abdomen, with uneven density, and multiple patchy cystic necrosis was seen inside. Considering the right upper abdominal mass, gastrointestinal stromal tumor is more likely (Figure 4)。 The tumor was mainly supplied by the branch of the abdominal aorta. According to the blood supply of the abdominal aorta and the location of the tumor, paraganglioma was not excluded. It was transferred to the urology department on March 26. Qualitative examination: urinary catecholamines (CA): norepinephrine (NE) 132.3 μ g/24 h, epinephrine (E) 6.3 μ g/24 h, dopamine (DA) 7 975.8 μ g/24 h (normal reference range: 120.9~330.6 μ g/24 h), all of which were significantly increased; Localization examination: Interadrenal medullary iodobenzguanidine imaging (MIBG) suggested an area equivalent to the right side of the middle abdomen with increased radioactivity, considered paraganglioma, with internal necrosis. Octreotide imaging showed high expression of somatostatin receptor in the right side of the middle abdomen, which considered the possibility of neuroendocrine tumor. Abdominal ultrasound on 31 Mar 2014: A 12.8 cm ×10.0 cm ×7.2 cm hypoechoic mass was seen on the right side of the abdominal aorta, in front of the renal vessels and the inferior vena cava in the right abdomen.

The patient was a 66-year-old male. He was admitted to hospital on March 3, 2015 due to "low back pain and discomfort for 10 days, headache, fever with gibberish for 5 days, and coma for 1 day". Lower back pain, accompanied by fatigue, no fever, no painful urination and urgency occurred without obvious trigger 10 days ago, which was not paid attention to. Fever occurred about 5 days ago, body temperature 37.7~38.6 ℃, accompanied by headache, bilateral temporal distension and pain, no cough and sputum, no vomiting, no convulsions, occasional gibberish, can quickly return to normal by itself, visited the local hospital, blood routine showed white blood cells 8.4×10⁹/L, the percentage of neutrophils was 0.92, C-reactive protein: 160 mg/L, the head CT showed "lacunar infarction in left parieto-occipital lobe", and the abdomen CT showed "liver abscess". There was no significant improvement after anti-inflammatory administration of "aloxicillin sodium". 1 d ago, the patient had headache, gibberish, irritability was worse than before, and then he became comatose, so he was transferred to the emergency department of our hospital. Since the onset of the disease, urine and defecation as usual, loss of appetite, and general sleep. He had a history of diabetes for 2 years and was not treated with regular medication. Denial of medical history such as hypertension. Denial of biliary stones or history of surgery. A family genetic history is denied. History of allergies denied.

Diabetes is a chronic syndrome caused by hyperglycemia, which affects the whole body and involves the nervous system, which is called diabetic neuropathy. Neuropathy may affect all somatic nerves, among which peripheral neuropathy, which is mainly distal limb paresthesia, is the most common. Neuralgia can occur in 6% of patients with diabetic peripheral neuropathy (DPN)^[1]painful diabetic neuropathy (PDN) is characterized by cautery-like, knife-like, insect bite-like, tear-like, and needle-like pain at night. The etiology and pathogenesis of PDN are still unknown, and it is generally believed that its occurrence is related to a combination of factors. In recent years, the role of inflammation in PDN has attracted more and more attention. The pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is highly expressed in the serum of patients with type 1 diabetes and type 2 diabetes, and the expression of TNF-α in DPN patients is significantly increased compared with that of patients with simple diabetes. The higher the level of TNF-α in patients with DPN, the more likely it is to complicate with painful neuropathy, and the higher the level of TNF-α in patients' serum, the more severe the pain response. TNF-α may be involved in the occurrence of diabetic painful neuropathy, leading to nerve ischemia, local nerve fiber demyelination, pain and heat hyperesthesia, etc. PDN care is complicated, and repeated hospitalization brings huge economic losses, which reduces the quality of life of patients, and can lead to non-traumatic amputation, high disability rate and mortality rate. At present, the only drugs approved by the US Food and Drug Regulatory Authority and the European Medicines Agency for the treatment of diabetic painful neuropathy are duloxetine and pregabalin^[2]。 Through the study of TNF-α, it is possible to find new potential therapeutic targets for diabetic painful neuropathy.

Aplastic anemia (AA) includes congenital and acquired, the former being Fanconi anemia; The latter is an acquired myelohematopoietic failure, characterized by myelohematopoietic failure, pancytopenia, and high mortality, but the exact etiology and mechanism remain unclarified. Recent studies have shown that its pathogenesis is related to the hyperfunction of autoimmune T cells. Autoreactive pathogenic T cells expand and activate, polarize to helper T cells (Th) 1 response and secrete a large number of inflammatory cytokines, directly or indirectly damage hematopoietic stem progenitor cells and bone marrow microenvironment. It is a class of T lymphocyte-mediated autoimmune diseases targeting hematopoietic system^[1,2]。

Lymphoproliferative diseases such as acute and chronic lymphocytic leukemia, lymphoma, multiple myeloma, etc. are difficult to diagnose. Among them, non-Hodgkin's lymphoma is the most complicated and confusing type of disease in pathological classification, and non-Hodgkin's lymphoma accounts for 89% of malignant lymphomas in China^[1]。 Techniques for diagnosis, efficacy and prognosis of non-Hodgkin's lymphoma mainly include conventional methods such as morphology, immunohistochemistry and cytogenetics. Immunophenotype analysis, including flow cytometry and immunohistochemistry, is the best auxiliary tool for the diagnosis of lymphoma. It plays a decisive role in the analysis of lymphoma subtypes, and also plays an auxiliary role in the judgment of lymphocyte clonal proliferation^[2]。 However, many lymphomas lack clonal proliferation markers, so immunophenotyping methods relying on these markers have certain limitations. It has been reported that approximately 5% to 10% of lymphoma cases are still difficult to obtain a final diagnosis after multiple phenotypic analyses^[3]At this time, it is necessary to rely on a molecular diagnostic technology, that is, the clonality analysis of receptor gene rearrangement to make a judgment^[4]。 Receptor gene rearrangement clonality analysis has been used in the diagnosis of lymphoma for nearly 30 years. Southern blot hybridization was initially used, but this method has strict requirements for specimen quality, large amount of tissue and complicated operation, so its clinical application is limited. Since 1990s, PCR has been used in the clonality analysis of recipient gene rearrangement and has gradually replaced Southern blot hybridization^[5,6]。 In recent years, researchers have improved the detection technology of recipient gene rearrangement mainly focusing on improving primers and establishing simpler and more accurate product analysis methods.