2018年 · 第98卷第05期

From the advent of Sipuleucel-T, the first autologous cellular immunotherapy drug, to the approval of Ipilimumab (anti-CTLA-4 monoclonal antibody) by the U.S. Food and Drug Administration (FDA) and the European Commission for the first-line treatment of advanced melanoma, solid tumor immunotherapy has gradually moved from behind the scenes to the front stage. From single targeting of tumor cells to including immune cells, the efficacy has made gratifying progress. There are various passive and active immunotherapies such as antibody-directed therapy and adoptive immunotherapy for tumor immunotherapy, which are also used in the field of glioma. This paper summarizes and evaluates some new important findings in glioma immunotherapy, in order to provide ideas and reference for more effective glioma immunotherapy.

Glioma refers to a tumor that originates from glial cells and is one of the most common primary intracranial tumors. Among them, glioblastoma (GBM) has the highest incidence rate, accounting for 46.1% of all gliomas, and the annual incidence rate is about 3.20/100,000. Modern comprehensive therapy, including maximal surgical resection, postoperative adjuvant concurrent chemoradiotherapy and chemotherapy (temozolomide: TMZ), can only delay the progression of glioblastoma, and the tumor inevitably recurs. The median progression time was 6.9 months, and the overall survival time was 14.6 months. The treatment effect was not satisfactory, and new treatment strategies were urgently needed. Targeted therapy mainly targets the already defined tumor cell oncogenic sites, from the gene to the protein molecular level, thereby inducing specific death of tumor cells. The cellular response after targeted therapy may or may not elicit the corresponding anti-tumor immune response of the body.

Acute myocardial infarction (AMI) is a common acute critical disease, often accompanied by abnormal changes in cardiac autonomic function^[1]Reperfusion therapy such as thrombolysis and emergency coronary intervention (PCI) can effectively improve myocardial blood supply and also affect autonomic nerve activity^[2]。 Autonomic nerve imbalance is associated with various complications such as arrhythmia, heart failure, shock and even sudden death^[3]At present, the evolution rule of autonomic nerve activity in the early stage of AMI is still unclear, especially the lack of research on the differences of autonomic nerve function in different infarcted vessels. This study observed the differences of autonomic nerve function in different periods of early stage of AMI caused by different infarcted vessels, and provided a basis for targeted treatment.

right heart thrombosis (RHT) refers to in situ thrombosis trapped in the right atrium, ventricle or right atrioventricle during deep vein thrombosis detachment. Most RHT patients are complicated with acute pulmonary embolism (APE). RHT is uncommon clinically, and although diagnosis is not difficult, there is no consensus on its treatment modalities (anticoagulation, thrombolysis, surgical thrombectomy)^[1]。 When APE is combined with RHT, the presence of the latter tends to influence physicians' decisions about APE treatment modalities. This study summarized and analyzed the clinical characteristics, echocardiographic findings and treatment outcomes of RHT patients admitted to Fuwai Hospital in recent years, aiming at improving the diagnosis and treatment level of clinicians for this disease.

reversible splenial lesion syndrome (RESLES) is a clinical imaging syndrome that mainly involves the corpus callosum due to various causes. 2011 by Garcia-Monco et al.^[1]Firstly, it is proposed that the MRI manifestation is a reversible transient diffusion-limited lesion involving at least the corpus callosum, accompanied by mild reversible clinical symptoms, with a self-limiting course and a favorable prognosis. We retrospectively analyzed 4 adult RESLES patients in Zhengzhou University People's Hospital to summarize their clinical characteristics and improve clinicians' understanding.

Case 1Female, 51 years old, farmer, was admitted to the Department of Neurology of Henan Provincial People's Hospital on June 13, 2016 with "fever, headache for 7 days and confused speech for 3 days". On June 7, 2016, he developed fever, headache, nausea and vomiting. On June 10, he developed gibberish, did not know his family, lost his direction when he went out, and appeared abnormal behaviors such as urinating in bed and eating unclean food. A history of clustered vesicular disease around the mouth and in front of the left ear 1 month ago. Physical examination lacks cooperation, spontaneous speech, inappropriate answers, poor orientation of characters, time and place, and lack of cooperation in physical examination of memory and computing power. The neck resisted 2 fingers, and the physical examination of the remaining nervous system showed no positive signs. Lumbar puncture was performed on the day of admission, pressure 118 mmH₂O (1 mmH₂O =0.009 8 kPa), colorless and transparent, white blood cell count 18×10⁶/L, 15×10 for mononuclear cells⁶/L, protein quantity 0.55 g/L, sugar and chloride content normal, tuberculosis antibody (-), antacid, ink, gram staining (-), virus antibody all (-), blood and cerebrospinal fluid immune encephalitis six antibodies (-). Cranial MRI + enhancement: Abnormal signals in bilateral amygdala, hippocampus, insula lobe and temporal lobe, and increased enhanced shadows of tenue meninges (Figure 1)。 Combined with the patient's past blister history, the onset was manifested by headache, abnormal mental behavior, slight increase in cerebrospinal fluid cell count and protein, and typical imaging findings, and the clinical diagnosis was herpes simplex virus encephalitis type 1. The patient was given acyclovir 0.625 g every 8 hours for antiviral treatment for 2 weeks. The patient's mental behavior abnormalities did not improve, and he still had persistent fever. The body temperature fluctuated from 37.5 to 38.2 ℃. On June 27, 2016, the white blood cell count of lumbar puncture was 60×10.⁶/L ↑, 57×10 for mononuclear cells⁶/L↑, protein quantification 0.77 g/L↑. The patient's symptoms did not improve, and the lumbar puncture result was worse than before. Considering the possibility of acyclovir resistance, the patient's symptoms improved dramatically with the addition of foscarnate sodium 3g once a day for antiviral treatment on the same day, and the body temperature dropped on the day of medication, with the highest body temperature not higher than 37.6℃. On June 29th, foscarnate sodium was changed to 3 g every 12 hours. Since July 1st, the body temperature has returned to normal, the nonsense has decreased, and the memory, orientation and computational power tests have improved. The lumbar puncture was reexamined on July 7, and the white blood cells were 18×10⁶/L, mononuclear cells 17×10⁶/L, protein 0.79 g/L. After 2 weeks of use of foscarnate, the patient's symptoms improved significantly, and the patient was discharged from the hospital with mild memory loss. On August 1st, the patient did not have fever again, and his memory, computing power and orientation force returned to normal.

A 43-year-old male was admitted to Shaoxing Central Hospital on February 16, 2016 due to repeated dizziness accompanied by unstable walking for 10 years and aggravation for 3 days. After admission, he was found to have hypoxemia and eventually died of lung infection and respiratory failure. Slow growth of young body mass, backward motor development, backward intellectual development, dropped out of school in the second year of junior high school, no similar cases in the family, parents are not close relatives, and the mother is healthy during pregnancy. Physical examination: weight 36 kg, height 137 cm, yellow hair, more pigmented spots on the face, dry skin, poor elasticity, subcutaneous fat, small eye clefts, moderately sunken eye sockets, pointed nose, pointed mandible, large auricle (Figure 1), rough hearing test decreased, cranial nerve physical examination was normal, muscle tone of both lower limbs increased, gait was unstable, tendon reflex was active, and pathological signs were negative. Auxiliary examination: Cranial CT showed cerebellar atrophy, calcification of cerebellar dentate nucleus and globus pallidus, and skull thickening (Figure 2)； ECG showed: sinus rhythm, left ventricular high voltage, pulmonary P wave, plain chest scan: infection of both lungs, left pleural effusion, scoliosis, slightly larger heart shadow, bilateral thoracodorsal muscle atrophy (Figure 3), cranial MR: brain atrophy (cortex, cerebellum), calcification of globus pallidus and cerebellar dentate nucleus (Figure 4), electrical audiometry showed sensorineural deafness, blood gas analysis showed hypoxemia, lung function showed mixed ventilatory dysfunction, residual blood, urine, stool, biochemistry, tumor markers, thyroid function, and autoimmunity were basically normal. According to clinical manifestations, signs and typical imaging changes, the final diagnosis of Cockayne syndrome (CS) was made. Due to the refusal of the patient's family, the patient did not undergo gene sequencing.

A 75-year-old male was found to occupy the left lobe of the liver on physical examination. On September 26, 2016, the abdominal CT examination at the Second Affiliated Hospital of Suzhou University showed that the left lobe of the liver was enlarged, the edge was irregular, and there was a huge mass-shaped slightly lower density focus, about 12.9 cm ×8.1 cm ×12.4 cm in size, irregular in shape and unclear in boundary. The CT value of plain scan was about 39 Hu. Multiple patchy lower density shadows and dotted calcification shadows were seen in the lesion, and the lower density shadows were scattered, with a CT value of about 2 Hu (FIG. 1A)； Multiple nodular obvious enhanced foci were found at the edge of the arterial phase of enhanced scanning (FIG. 1B)； In the venous phase and the delayed phase, the enhancement was filled into the interior of the lesion, and the partial enhancement of the lesion parenchyma was slightly higher than that of the liver parenchyma, but the lower density shadow in it did not show significant enhancement (Figure 1C，Figure 1D，Figure 1E)； Multiple low-density foci of different sizes were also seen in the liver, but no obvious enhancement was found on enhancement scan. CT diagnosis is: the left lobe of the liver occupies space, which is considered as hepatic hemangioma/hepatic angiosarcoma; Multiple cysts of the liver; Schistosomiasis liver disease. After admitting to the general surgery department of our hospital, there was no abdominal pain, slight distension, nausea and vomiting, fear of cold and fever and other discomfort during the course of the disease. Laboratory tests: There were no abnormalities in blood routine and biochemical routine, and tumor markers such as alpha-fetoprotein, carcinoembryonic antigen and CA199 were all normal. Left hemihepatectomy under general anesthesia. Surgical findings: the left lobe of the liver was enlarged, the edge was not smooth, there were no enlarged lymph nodes around it, and no metastases were detected in the abdominal cavity; Pathological macroscopic findings: a piece of gray-red tissue, about 12 cm ×9 cm ×13 cm in size, with bloody viscous liquid inside, soft and multilocular; Hematoxylin-eosin staining: Microscopically, a large number of different types of dilated vascular lymphatic vessels lined with flat endothelial cells (Figure 2)； Immunohistochemistry: CD34 (+), CD31 (+), D2-40 (+), Ki67 (+, about 10%). Pathological diagnosis: hepatic angioma.

The idea of evidence-based clinical practice has gradually penetrated into clinical practice and guided the clinical practice process. More and more doctors and researchers are paying attention to evidence-based medicine research^[1]。 Co-decision-making (SDM) fully embodies the idea of evidence-based medicine, and is an advanced evidence-based clinical practice concept. It has been widely concerned and applied abroad, and its development in China still needs to be improved.

pediatric low-grade gliomas (PLGG) are the most common type of brain tumors in children, accounting for about 25% of all kinds of intracranial tumors in children^[1]。 The histopathological types of PLGG are diverse, including the most common pilocytic astrocytoma (PA, WHO grade I), pleomorphic xanthroastrocytoma (PXA, WHO grade II), diffuse astrocytoma (DA, WHO grade II), ganglioglioma (GG, WHO grade I), dysembroplastic neuroepithelial tumor (DNET, WHO grade I), Angiocentric glioma (AG, WHO grade I), oligedendroglioma (OG, WHO grade II), and rarely subependymal giant cell astrocytoma (SEGA, WHO grade I) complicated by tuborous sclerosis syndrome (TS). Surgical treatment is the first choice and core treatment in PLGG except NF1-related tumors. Chemotherapy is used when the tumor remains or progresses after surgery. Because radiotherapy may affect the neurodevelopment and cognitive function of children, it has been rarely used at present. The overall prognosis of PLGG was favorable, with 5-and 10-year overall survival rates exceeding 90% and 70%. However, because of the long postoperative survival period and insensitivity to chemotherapy and radiotherapy, there is still a high pathogenicity rate and affects children's learning and quality of life.

Prostate cancer (PCa) is one of the most common malignant tumors in men, with the worldwide incidence and mortality ranking second among male malignant tumors^[1]。 For most patients with intermediate and advanced PCa, endocrine therapy is the main method, but after 14 to 30 months of treatment, it gradually develops into metastatic castration-resistant prostate cancer (mCRPC)^[2]。 The traditional treatment for mCRPC is docetaxel chemotherapy^[3]However, there are many adverse reactions, and even bone marrow suppression occurs in severe cases. The emerging PCa immunotherapy is an effective means after surgery, radiotherapy, chemotherapy, endocrine and targeted therapy.

There is a class of B cells in the human body that play a negative role in regulating the body's immune response. Such B cells are called regulatory B cells (Bregs). Through the study of different immune disease models, it was found that there are many types of Bregs with different phenotypic characteristics in human body, and they can mediate the negative regulation of immune response through the interaction between secreted cytokine granzyme and cell surface molecules. At present, it is mainly believed that Bregs are transformed by B cells at different stages of differentiation and development receiving different signals. Defects in the number and function of Bregs can be detected in a variety of immune diseases; The negative regulation of immune process is expected to make Bregs a new target of immunotherapy, providing therapeutic ideas for many refractory chronic infections, tumors and immune diseases.