Volume 98  ·  Issue 05  ·  2018

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.

To explore the prognostic impact of 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors on patients with low grade gliomas (LGG).

A total of 482 patients diagnosed with LGG in Beijing Tiantan Hospital affiliated to Capital Medical University from January 2009 to May 2016 were pathologically reclassified and retrospectively reviewed. In the survival analysis, Kaplan-Meier Plot was used to univariate analysis and Cox proportional hazards model was used to multivariate analysis.

According to the 2016 WHO CNS criterion, a total of 232 LGG were reclassified as O 1p/19q-deleted and IDH-mutant, 134 as A IDH-mutant and 116 as A IDH-wildtype. Univariate analysis showed that 2016 WHO CNS divided LGG into three subgroups with distinct survival (P<0.001). Multivariate analysis showed that both 2007 WHO CNS and 2016 WHO CNS were independent prognostic factors, but the Hazard ratio (HR) of 2016 WHO CNS was significantly higher than that of 2007 WHO CNS (P<0.01).

2016 WHO CNS classification criteria can divide LGG into three subgroups with significantly distinct survival, which has further improved the clinical prognostic value of it and fully reflected its advantages in predicting prognosis.

To investigate the changes of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time(TT), fibrinogen(FIB) and platelet counts(PLT) in plasma of patients with glioma, and to explore the correlations between PT, APTT, TT, FIB and PLT with malignant grades of glioma.

One hundred and seventy-two patients with glioma and 47 health controls were investigated in a retrospective analysis. All patients were diagnosed and identified the WHO grade by pathologist after operation. Including 40 cases with glioblastoma multiforme, WHO Ⅳ grade, 45 cases with anaplastic astrocytoma, WHO Ⅲ grade, 46 cases with astrocytoma and oligodendroglia astrocytoma, WHO Ⅱ grade, and 41 cases with pilocytic astrocytoma.

PT was significantly shorter in patients with WHO Ⅰ-Ⅳ grade glioma than that in normal controls (P<0.05); APTT was significantly shorter in patients with WHO Ⅲ and Ⅳ grade glioma than that in normal controls and WHO Ⅰ grade glioma patients (P<0.05); FIB of WHO Ⅳ grade glioma was higher than that in normal control and WHO Ⅰ to Ⅲ grade glioma (P<0.05). While, there was no significant difference of TT and PLT among patients with WHO Ⅰ to Ⅳ and normal controls (P>0.05). Spearman correlation analysis showed that there was negative correlation between APTT and WHO grade (r=-0.200, P=0.007) as well as positive correlation between FIB and WHO grade (r=0.175, P=0.020); Pearson linear correlation analysis showed that there was negative correlation between APTT and Ki67 in patients with glioma.

the levels of FIB and APTT in patients with glioma were correlated with WHO grade of glioma, and higher FIB, shorter APTT and PT in patients with WHO Ⅳ grade glioma indicated that there exist hypercoagulation states.

To investigate the correlation between nucleolus spindle-related protein 1 (NUSAP1) and malignant progression and prognosis of human glioblastoma multiforme (GBM).

RT-PCR and immunohistochemical technique were applied to analyze NUSAP1 expression level in GBM surgical specimens. Correlations between NUSAP1 expression and molecular classification and survival of patients with GBM were also investigated in TCGA database. The gene silencing technique was used to silence NUSAP1 expression in U87 cells, CCK-8 assay was used to detect cell proliferation, flow cytometry was used to detect cell cycle changes, and in vivo tumorigenicity was evaluated after NUSAP1 silencing in tumor-bearing mice.

NUSAP1 expression level in GBM was higher than that in non-tumor brain tissue. Survival curve analysis showed that the survival time of GBM patients with high NUSAP1 expression decreased significantly (P<0.01). NUSAP1 expression was relatively lower in mesenchymal and neural molecular subtypes of GBM, when compared with the other two molecular subtypes. And it was closely related with specific genetic aberrations (such as PTEN loss and IDH1 mutation). Silencing NUSAP1 inhibited G2/M cell cycle progression of GBM cells, and inhibited cell proliferation both in vitro and in vivo.

Expression of NUSAP1 is closely related to progress and prognosis of GBM, and can be a biomarker reflecting GBM prognosis and act as a therapeutic target with potential clinical application value.

To evaluate the application value of intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) in detecting early-stage diabetic nephropathy and to assess the damage of ralated renal function.

A total of 52 patients with type 2 diabetes diagnosed in Zhongda Hospital were collected from April 2016 to May 2017 and were assigned to DM group (diabetes without nephropathy, n=32) and DN group (diabetes with nephropathy, n=20) according to detection of microalbuminuria, a cohort of healthy recipients were included as control group (n=27) in the meantime. All of the subjects underwent IVIM and DTI examination. The cortical and medullary parameters[IVIM: perfusion fraction f, tissue diffusivity D, pseudodiffuvisity D^*; DTI: fractional anisotropy FA, apparent diffusion coefficient ADC, principal diffusivities (λ1, λ2, λ3)]were obtained respectively and were compared among groups. The relationship between MRI related parameters and estimated glomerular filtration rate (eGFR) were statistically investigated; and diagnostic performance of IVIM and DTI in discriminating DM and DN group was evaluated by receiver operating characteristic analysis.

The cortical and medullary f, D values in DN group were lower than those in DM group and control group (F=17.32, 15.69, 6.71, 10.94, all P<0.05). D values of all subjects showed positive correlations with eGFR (cortexr=0.518, medulla r=0.538, both P<0.05). The diagnostic efficiency of cortical f values to discriminate diabetes and diabetic nephropathy was 0.817, the cut-off value was 0.205. The medullary FA value in DM group was lower than that in control group ((0.371±0.051 vs 0.423±0.043,t=4.188, P<0.05); and the medullary FA value in DN group (0.315±0.062) was lower than that in control and DM group (F=25.08, P<0.05). The medullary λ3 values in DM group and DN group were all significantly higher than that in control group (F=7.86, P<0.05). The diagnostic efficiency of medullary FA values to discriminate diabetes and diabetic nephropathy was 0.763, the cut-off value was 0.344.

IVIM and DTI can reflect the abnormal perfusion and diffusion during early-stage diabetic nephropathy and have the potential value to assess the damage of ralated renal function.

To explore the short-term effects of expanded anterolateral approach in treating fracture involved the posterolateral tibial plateau.

A retrospective analysis of the clinical data from 16 patients undergoing extended anterolateral approach for fracture involved the posterolateral tibial plateau in the First Affiliated Hospital of Wannan Medical College between January 2013 and July 2016 was done. The patients were treated with 3.5 mm proximal "L" type proximal tibial locking compression plate with four locking screws through the nail row technique. The X-rays examinations were carried out immediately after the operation and at 1.5, 3, 6, and 12 months later, to continuously measure the tibial plateau angle (TPA) and posterior slope angle (PA). The Rasmussen radiology score was used to assess the reduction. One year later, the modified Rasmussen knee score was used to assess the recovery of knee function, the Lysholm score was applied to evaluate the cartilage injury, softening and degeneration, and lateral stress test and dial test were carried out to evaluate the stability of the knee.

The group consisted of 11 males and 5 females; aged 25 to 71 years, mean (47±12) years; schatzker type Ⅱ 9 cases, type Ⅴ 6 cases and type Ⅵ 1 case. There were 9 cases of type B in Orthopedic Trauma Association (OTA) classification, and 7 cases of type C. X-ray was immediately performed after operation and it showed that 14 cases got anatomic reduction, 2 cases left<2 mm of steps. Rasmussen radiology score was 14 to 18 points, mean (17.0±1.5) points. X-ray examination showed no significant difference in TPA immediately after operation and 1.5, 3, 6, 12 months later (F=0.05, P=0.99), and there was no significant difference in PA among the time points (F=0.02, P=1.00). At one-year of follow-up, the modified Rasmussen knee score ranged from 18 to 29 with an average of (25.0±3.3) points, of which 7 were excellent, 8 were good and 1 was fair. The excellent and good rate was 93.75%. Knee range of motion was 110°-135° with a mean of (122±8)°. Lysholm score was 93±4. Evaluation of lateral stress test and dial test were both negative.

The short-term curative effect of expanded anterolateral approach in treating fracture involved the posterolateral tibial plateau with the 3.5 mm proximal "L" type proximal tibial locking compression plate proximal to the locking screw is satisfactory, it provides sufficient exposure and effective fixation, the joint function and stability are satisfying.

To compare the effect of proximal femoral nail anti-rotation and dynamic hip screw in treating the femoral intertrochanteric fractures in elderly patients.

From June 2011 to June 2014, totally 158 elderly patients of femoral intertrochanteric fracture were treated by surgery, among whom 68 cases were treated with dynamic hip screws (DHS), and 90 patients were treated with proximal femoral nail anti-rotation (PFNA). The operative time, hospitalization time, weight-bearing time, fracture-healing time, blood loss and the hip function score after the operation were compared between the two groups by using the t test; and the incidence of the postoperative complication was compared between the two groups by using the Chi square test.

All the patients were followed-up for 6 to 18 months (12. 6 months on average). There was no statistic differences in the gender, age, the surgical time after injury and the fracture type between the two groups (χ²=0.025, t=1.461, 1.329, χ ²=2.070, all P>0.05). While, the operative time, blood loss, hospitalization time and the weight-bearing time in the PFNA group were all significantly lower than those in the DHS group[(47±14) vs (114±20) min, (121±26) vs (281±44) ml, (10.2±3.3) vs (13.5±2.8) d, (29±8) vs (53±10) d,t=8.376, 6.669, 2.176, 2.664, all P<0.05]; and the Harris hip score of 6 months post operation in PFNA group was significantly higher than that in the DHS group (90±17 vs 87±15,t=2.337, P<0.05). However, no significant difference in fracture healing time was found between the two groups[(11.8±2.3) vs (12.2±2.7) weeks,t=1.114, P>0.05]. Moreover, the incidence of complications in the DHS group was 16.2% while it was 7.8% in the PFNA group, the latter was obviously lower (χ²=4.801, P<0.05).

DHS is suitable for the patients with good physical condition or for the patients with stable fracture types. While, PFNA has the advantages of firmly fixation, less tissue damage, lower complications and wide indications. So, it is superior in the femoral intertrochanteric fractures.

To investigate the potential pathogenesis of acute paraplegia resulting from intrathecal chemotherapy and to analyze the factors influencing prognosis.

Six cases presented with acute paraplegia after intrathecal chemotherapy for leukemia from January 1^st, 2015 to June 1^st, 2017 in our hospital. The patients′ clinical manifestation, data of imaging and cerebrospinal fluid were analyzed.

Six patients with leukemia were with an average age of 27.3 (7 to 55) years old. Four cases were intrathecally injected with cytarabine, and two cases were intrathecally injected with cytarabine and methotrexate. Paraplegia occurred in 5 patients during or immediately after the injection; pain occurred in 1 patient immediately after the injection followed with paraplegia 2 h later. Four patients underwent MRI scan of the spinal cord but failed to show responsible lesions. The youngest patient who received the most frequent intrathecal injections, the highest dosage of cytarabine, combination with methotrexate set up the most serious symptoms and the poorest prognosis.

Cytarabine has close relationship with the occurrence of paraplegia. The possible risk factors of poor prognosis might be younger age, more frequent injections, higher dosage, combination of cytarabine and methotrexate.

To investigate the clinical features and survival of multiple myeloma-associated amyloidosis patients.

Twenty three multiple myeloma-associated amyloidosis patients were retrospectively analyzed from January 2009 to December 2016.

The overall response rate(ORR)was 65.2% and the remission rate (sCR+ CR) was 21.7%. The median progression-free survival(PFS) was fourteen months(1-63), and the median overall survival(OS)was fifteen months(3-63). The early death rate (death rate within one year)was 33.3%. The median OS of patients(n=9)with the performance status(PS) score >2 was seven months(1-15), and the median OS of patients( n=14)with the PS score ≤2 was thirty months(10-63). There was a statistically significant difference in OS(P<0.05); the median PFS and OS of the patients (n=15) who responded to inductive treatment were seventeen months(2-63) and twenty four months (4-63)respectively, and the median PFS and OS of the patients (n=8)who did not respond to inductive treatment were three months(1-8) and eleven months (3-15) respectively. There was a statistically significant difference in PFS and OS(P<0.05). There was a statistically significant difference in PFS and OS between patients treated with remission (n=5)and those who did not(n=18) (P<0.05).

The multiple myeloma-associated amyloidosis patients had a high early death rate and short survival time. Early identification and effective treatment are the preconditions for improving the poor prognosis.

To investigate the role and mechanism of IL-17 and CXCR4 in chronic graft nephropathy (CAN) in rat models.

CAN rat models were established using Fisher 344 to Lewis rats. In the control group(n=10), Lewis rats were performed isotransplantation. CAN rat models were established in experimental group(n=10). All the rats were havested 6 weeks after transplantation. Kidneys were examined by pathology to evaluate the injury of the renal allograft. SDF-1/CXCR4, IL-17 and α-SMA expression level in serum and renal graft were detected by immunohistochemical staining and Enzyme-linked immunosorbent assays(ELISA). The percent and the absolute amount of CD4 ⁺ cells、CXCR4⁺ cells and IL-17⁺ cells were detected by flow cytometry.

The graft of the experiment group showed obvious pathological features of CAN. The protein expression levels of SDF-1/CXCR4 and IL-17 in the experiment group are significantly higher than in the control group. We could also observe the number of Th17 cells has a significant increase in the experiment group[blood (0.19±0.05)% vs (0.12±0.03)%; kidney (0.52±0.21)% vs (0.17±0.12)%]. The IL-17 level also showed the same differences between the experiment[blood (243.12±17.63) pg/ml, kidney (521.54±21.76) pg/ml]and the control group[blood (35.78±7.3) pg/ml, kidney (77.34±11.1) pg/ml].

The Th17 cells increase in the CAN rats model, maybe the SDF-1/CXCR4 has a chemotaxis to collect Th17 cells to the injured kidney. And its expression of IL-17 may promote the renal cells to transform into fibroblasts.

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.