Prevention of central cell damage to isolated islets of Langerhans in hamsters by low temperature preconditioning

BACKGROUND: The efficacy of clinical islet transplanta- tion has been demonstrated with autografts, and although islet allografts have established insulin independence in a small number of IDDM patients, the treatment is con- founded by the necessity of central cell damage immuno- suppression, the lack of donor tissue, and recurring islet immunogenicity. These limitations underscore a need to develop therapies to serve the large population of diabetic patients. This study was designed to document central cell damage to isolated islets of Langerhans in hamsters and its prevention. METHODS: Islets were cultured at 37 °C for 7-14 days after isolation, and then at 26 °C for 2,4 and 7 days before addi- tional culture at 37 °C for an additional 7 days. Central cell damage in the isolated islets was monitored by video-mi- croscopy and analyzed quantitatively by a computer-assis- ted image analysis system. The analysis included daily measurement of the diameter and the area of the isolated is- lets and the area of the central cell damage that developed in those islets over time during culture. Histological exami- nation and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to characterize cell damage and to monitor islet function. RESULTS; Microscopic analysis showed that during the 7 to 14 days of culture at 37 °C, central cell damage appeared in the larger islets with diameters greater than 200 μm, which included both necrotic and apoptotic cell death. Low temperature (26 °C) culture prevented central cell damage of isolated islets. The 7-day culture procedure at 26 °C could inhibit most of the central cell ( excluding diameters greater than 300 μm) damage when the islets were re- warmed to 37 °C. CONCLUSIONS: Our results indicate that central cell da- mage to isolated islets of Langerhans correlates with the size of the islets. Low temperature (26 °C) culture can preventcentral cell damage to the isolated islets, and is capable to successfully precondition these islets for 37 °C culture. These novel findings may help to understand the patho- physiology of early loss of islet tissue after transplantation, and may provide a new strategy to improve graft function in the clinical setting of islet transplantation.

Central Granular Cell Odontogenic Tumor: A Literature Review of Cases Reported in the Last 71 Years with a New Case Report

Central granular cell odontogenic tumors(CGCOTs)are rare,benign,slowly growing odontogenic neoplasms.Due to their uncertain histogenesis,CGCOTs are still not included as a distinct entity in the WHO classification(2017)of odontogenic tumors.We report a case of CGCOT involving the right side of maxillary anterior region of a 39-year-old white female.Immunohistochemical staining showed that granular cells positively expressed CD68 and vimentin,and negatively expressed S-100 protein.Meanwhile,we searched Pub Med,Google Scholar,and Scopus databases to summary the clinico-pathological features of 51 reported cases of CGCOT.The results showed that the granular cells of 28.6%cases were immunopositive for vimentin and CD68,and odontogenic epithelial cells were positive immunoreactivity for cytokeratin.These findings reinforced the mesenchymal origin of granular cells and the odontogenic nature of epithelium islands.

Fertilization in Torenia fournieri:actin organization and nuclear behavior in the central cell and primary endosperm

Studies of the living embryo sacs of Torenia fournieri reveal that the actin cytoskeleton undergoes dramatic changes that correlate with nuclear migration within the central cell and the primary endosperm. Before pollination, actin filaments appear as short bundles randomly distributed in the cortex of the central cell. Two days after anthesis, they become organized into a distinct actin network. At this stage the secondary nucleus, which is located in the central region of the central cell, possesses an associated array of short actin filaments. Soon after pollination, the actin filaments become fragmented in the micropylar end and the secondary nucleus is located next to the egg apparatus. After fertilization, the primary endosperm nucleus moves away from the egg cell and actin filaments reorganize into a prominent network in the cytoplasm of the primary endosperm. Disruption of the actin cytoskeleton with latrunculin A and cytochalasin B indicates that actin is involved in the migration of the nucleus in the central cell. Our data also suggest that the dynamics of actin cytoskeleton may be responsible for the reorganization of the central cell and primary endosperm cytoplasm during fertilization.

The clinical characteristics and treatment outcomeof 57 children and adolescents with primary central nervoussystem germ cell tumors

Primary central nervous system germ cell tumors(CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years(range, 2.7 to 18.0 years) at diagnosis; 43(75.4%) had non-germinomatous germ cell tumors(NGGCTs) and 14(24.6%) had germinomas; 44(77.2%) had localized disease and 13(22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB(cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months(range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival(EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs(P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively(P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

Corneal endothelial cell density and morphology and central corneal thickness in Guangxi Maonan and Han adolescent students of China

AIM: To investigate the corneal endothelial cell density and morphology and central corneal thickness in the Guangxi Maonan and Han adolescent students of China.METHODS: Noncontact specular microscope(Topcon SP3000 P, Tokyo, Japan) was performed in 133 adolescent students of Maonan ethnic group(M:F 54:79)and 105 adolescent students of Han ethnic group(M:F 50:55),5 to 20 y of age, who were randomly selected from 3schools in Huanjiang Maonan Autonomous County of Guangxi Zhuang Autonomous Region of China.Parameters studied included endothelial cell density,mean cell area, coefficient of variation in cell size,percentage hexagonality and central corneal thickness. RESULTS: Endothelial cell density, mean cell area,coefficient of variation in cell size, percentage hexagonality and central corneal thickness in the study population were(2969.50 ±253.93) cells/mm2,(339.23 ±29.44) μm2,(29.96 ±4.07) %,(64.58 ±9.41) % and(523.71 ±32.82) μm in Maonan and(2998.26 ±262.65) cells/mm2,(336.11±30.07) μm2,(29.89±5.03) %,(64.91±11.64) % and(524.39 ±33.15) μm in Han, respectively. No significant differences were observed in endothelial cell density,mean cell area, coefficient of variation in cell size,percentage hexagonality and central corneal thickness between Maonan and Han(P =0.615, 0.659, 0.528, 0.551,0.999). In Maonan and Han, we found age was negatively correlated with endothelial cell density and percentagehexagonality and positively correlated with mean cell area and coefficient of variation in cell size. Negative correlation was also found between central corneal thickness and age in Han, whereas no correlation was found in Maonan. CONCLUSION: There were no differences between Maonan and Han in corneal endothelial cell density and morphology and central corneal thickness. In these two ethnic groups, there were statistically significant decrease in endothelial cell density and percentage hexagonality with increasing age and statistically significant increase in cell area and coefficient of variation in cell size with increasing age. Central corneal thinned with increasing age in Han, whereas difference did not attain statistical significance in Maonan.

Surgical Treatment of Central Giant Cell Granuloma with Carnoy’s Solution

A 25-year-old woman presented a unilateral mandibular swelling, after laboratory analysis, radiological studies and aspiration puncture biopsy, the pathological diagnosis of Central Giant Cell Granuloma was made. Radiographically, the multilocular lesion involved the left lower first molar and was 30 mm long by 20 mm high. Dental extraction of the molar involved with forceps and exeresis in toto of the tumor were performed using a Volkmann cutting curette. The tumor made up of 90% vascular tissue produced intra-surgical bleeding that made visibility difficult. The bone bed curettage was aggressive except for its base in direct contact with the inferior dental nerve. Subsequently, to avoid recurrence, the surgical protocol includes a double irrigation with Carnoy’s solution, (fixative composed of 60% ethanol, 30% chloroform and 10% glacial acetic acid 98%) for 5 minutes that produces chemical cauterization. Finally, it was washed with physiological solution and the cavity was filled with iodoformed gauze. The gauze was exchanged and removed gradually over three weeks for second intention healing. This case is presented to demonstrate that inexpensive chemical treatment can be safely used for outpatient surgery under local anesthesia. Because Carnoy’s solution achieved control of intraoperative bleeding, allowed bone healing and prevented recurrence of the lesion in clinical radiographic follow-up for 15 years.

Extracellular vesicles in the diagnosis and treatment of central nervous system diseases

Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems.In many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic proteins.The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases.Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier.Today,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well evidenced.Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative diseases.Depending on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and anti-inflammatory.Due to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain.This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.

Metabolic peculiarity of^（134）Cs and its radioimmunotoxicological effect on central and peripheral immune cells

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The emerging roles of transplanted radial glial cells in regenerating the central nervous system

Scientists conclude that a combination of treatments involving rehabilitation,drug delivery,surgery and cell transplantation are necessary to achieve significant progress in regenerating the injured central nervous system（CNS）.

Unusual aggressive behavior of central giant cell granuloma following tooth extraction

Central giant cell granuloma(CGCG) is found exclusivelyin jaws. Its etiopathogenesis is unclear; however it is suggested that it can arise as a reactive response to trauma. This report describes an aggressive variety of CGCG which raises a question; can extraction of tooth modify the behavior of CGCG? A 46 years old male had reported with a rapidly increasing intraoral and extraoral swelling of lower jaw following tooth extraction. Radiographic examination revealed a large multilocular lesion involving the body and ramus of mandible which had been proved to be aggressive CGCG on histopathological examination. The importance of radiographic examination prior to extraction of teeth and importance of inclusion of CGCG in jaw swellings associated with mobility of teeth or failure of healing sockets is emphasized.

Central Upwind Scheme for Solving Multivariate Cell Population Balance Models

Microbial cultures are comprised of heterogeneous cells that differ according to their size and intracellular concentrations of DNA, proteins and other constituents. Because of the included level of details, multi-variable cell population balance models (PBMs) offer the most general way to describe the complicated phenomena associated with cell growth, substrate consumption and product formation. For that reason, solving and understanding of such models are essential to predict and control cell growth in the processes of biotechnological interest. Such models typically consist of a partial integro-differential equation for describing cell growth and an ordinary integro-differential equation for representing substrate consumption. However, the involved mathematical complexities make their numerical solutions challenging for the given numerical scheme. In this article, the central upwind scheme is applied to solve the single-variate and bivariate cell population balance models considering equal and unequal partitioning of cellular materials. The validity of the developed algorithms is verified through several case studies. It was found that the suggested scheme is more reliable and effective.

Successful Treatment of Elderly Diffuse Large B-Cell Lymphoma with Central Nervous System Recurrence by Rituximab, Ranimusutine, Ifosfamide, Procarbazine, Dexamethasone, and Etoposide Therapy

The prognosis of CD20-positive (CD20+) diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) recurrence is still poor. A standard treatment for CD20+ DLBCL with CNS recurrence in elderly patients has not been established mainly due to adverse effects. We previously reported the efficacy and safety of MIND-E (ranimustine, ifosfamide, procarbazine, dexamethasone, and etoposide) therapy for elderly CD20+ DLBCL patients with CNS recurrence. Here, we report the use of R-MIND-E therapy (rituximab, ranimustine, ifosfamide, procarbazine, dexamethasone and etoposide) in an elderly CD20+ DLBCL patient with CNS recurrence. The patient achieved a complete response according to Revised Response Criteria for Malignant Lymphoma, and treatment-related toxicity was tolerable. R-MIND-E therapy may be a feasible and useful treatment option for elderly CD20+ DLBCL patients with CNS recurrence.

Early management of sickle cell anemia in central Africa:is it possible?

Sickle cell disease(SCD) is a worldwide hemoglobinopathy that concerns about 250000 affected children everv year.The majority of them are living in tropical regions,particularly in sub-Saharan Africa,India and Middle East.Life expectancy and quality of life of SCD patients have improved since the newborn screening and early management have been introduced in USA and Jamaica.Experts of hemoglobinopathies strongly encouraged WHO to develop in the endemic areas networks based on the Thalassaemia International Federation(TIF) model in order to conduct activities for developing medical services for care and prevention of hemoglobin disorders. Despite the inherent practical,political and economic difficulties,early diagnosis and a comprehensive health care program for SCD could be implemented in most of the African countries where the prevalence is high;but many challenges have to be first resolved.Based on pilot studies conducted in some central African countries,this article proposed some strategies and discusses the different ways of implementing initiatives that are indispensable for decreasing the mortality and morbidity rate of SCD in Central Africa.

Incidence of Sickle Cell Anaemia and Thalassaemia in Central India

Haemoglobinopathies are group of diseases characterized by abnormalities both quantitative and qualitative in the synthesis of haemoglobin. Haemoglobinopathies consist of sickle cell anaemia (SCA), thalassaemia (βT) and variant haemoglobins. In India, they are responsible for the largest number of genetic disorders and hence are of great public health hazardous. In India major concerned haemoglobinopathic disorders are sickle cell anaemia and β-thalassaemia. Of the several abnormal haemoglobin molecules, four which are widely prevalent in India include: HbS, HbβT, HbE and HbD. Examination of 6463 individuals showed high incidences for haemoglobin variants, HbS and HbβT in different ethnic groups, the frequency being varies from 0% - 20% and 0% - 9% respectively. The frequency of HbS in Brahmins is 4.17%, in Kalar 5.41%, in Rajput 2.04%, in Muslims 3.73% in Maratha 2.08% in Bania 9.09% while in Teli it is 3.65%. Among the Scheduled castes and Nomadic tribal groups HbS ranges from 1% - 12%;in backward caste categories it varies from 3% - 16%;while in Scheduled tribes it ranges from 0% - 20%. The high magnitude of sickle cell trait has been noticed in the Pardhan (20.31%) followed by the Marar (16.10%), the Dhiwar (11.90%), the Gond (11.89%), the Mahar (11.81%) and the Bania (9.90%). A considerable high frequency (9.27%) of β-thalassaemia has been observed among the Sindhi population. Sporadic occurrence of HbβT and HbD among other communities suggested the gradual spread of the genes into the region. The present findings in 11 communities with the thalassaemia syndrome suggest that the β-thalassaemia is accompanied by raised level of HbA2. Unusual greater mean RBC and WBC suggest the high concentration of hypochromic microcytosis in anaemia. The mean MCV and MCH in HbβT and HbD are much lower than the normal ranges compared to HbS. The mean MCHC is much lower in HbβT, HbDD and HbS than the normal range. The cumulative gene frequency of haemoglobinopathies in India is 4.2%. With a population of over 1 billion and a birth rate of 28 per 1000, there are over 42 million carriers and over 12,000 infants are born each year with a major and clinical significant haemoglobinopathy. Out of these, clinically significant sickle cell anaemia and β-thalassaemic disorders account for almost equal numbers.

Durable response to pulsatile icotinib for central nervous system metastases from EGFR-mutated non-small cell lung cancer: A case report

BACKGROUND Central nervous system(CNS) metastases are a catastrophic complication of nonsmall cell lung cancer(NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains challenging.CASE SUMMARY We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor(EGFR). A standard dosage of icotinib(125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib(1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side effects.CONCLUSION This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases.

Cell-type specific examination of central amygdala dopamine receptor 2 expressing neurons as a translational target for pharmacological enhancement of extinction

Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders.Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in humans.Here we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA populations.Sequencing of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and Adora2a.Direct pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.

胸腔镜支气管袖式成形肺叶切除术治疗中央型小细胞肺癌的效果

目的探讨胸腔镜支气管袖式成形肺叶切除术治疗中央型小细胞肺癌的效果。方法选取2019年1月至2020年5月于郑州大学第一附属医院接受治疗的中央型小细胞肺癌患者82例作为研究对象,分为观察组(接受胸腔镜支气管袖式成形肺叶切除术)与对照组(接受传统手术治疗),各41例。对比患者围手术期相关指标、并发症发生率、生存率、无进展生存时间及复发率。分析视觉模拟评分法(VAS)及Karnofsky功能状态评分(KPS)。结果观察组术中出血量(231.49±23.56)mL、胸腔引流量(902.20±102.39)mL,均少于对照组[(302.17±30.41)mL、(1145.32±172.41)mL],而术后引流时间(6.15±1.41)d、住院时间(11.41±2.49)d短于对照组[(7.10±1.93)d、(13.56±3.24)d](P<0.05);观察组术后并发症发生率、复发率、VAS评分低于对照组,KPS评分高于对照组(P<0.05)。观察组的无进展生存时间长于对照组(P<0.05)。结论胸腔镜支气管袖式成形肺叶切除术治疗有利于降低并发症发生率和延长无进展生存时间。

细胞凋亡、坏死和焦亡信号网络关键节点的识别

细胞死亡作为一项基本的生命过程,在生物体的发育、自稳态和病理方面有重要作用.寻找细胞死亡信号通路中的关键节点一直是领域的研究焦点,而信号网络的构建及分析可为其提供重要的理论参考.主要关注凋亡、坏死和焦亡这3种研究最多的细胞死亡方式.首先从已发表文献和生物信息数据库中获取初步数据,对数据进行文本处理,利用处理后的数据构建凋亡、坏死和焦亡的信号网络.然后分别计算各网络的度中心性、介数中心性、接近中心性和特征向量中心性指标,并利用k-壳分解和社团发现方法对节点进行不同的划分.最终综合上述方法所得结果,鉴定出各网络中的关键节点.

佐利替尼一线治疗EGFR突变NSCLC伴中枢神经系统转移2例报告

目的探讨佐利替尼一线治疗具有原发表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)伴中枢神经系统转移患者的疗效。方法2例患者均为一线使用佐利替尼,通过实体瘤的疗效评价标准RECIST v1.1和神经系统肿瘤脑转移RANO-BM标准评估肿瘤治疗反应。结果病例1基线伴多发脑转移,EGFR exon 19del突变,佐利替尼治疗51.4个月后仍维持肺部病灶部分缓解(PR)、颅内病灶完全缓解(CR)。病例2基线单个脑转移病灶,EGFR exon 19del突变,佐利替尼治疗期间达到肺部病灶PR、颅内病灶CR,13.7个月后肺部疾病进展(PD),新发单个脑转移病灶,综合评效PD。病例1出现3级不良反应,为皮肤干燥,其余主要为皮疹、肝功能异常、腹泻,不良反应总体可控。结论佐利替尼对EGFR突变NSCLC伴中枢神经系统转移患者有较好的颅内及颅外病灶的控制效果,与EVEREST研究一致,可作为一线初始治疗的选择。