1.Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance
Xianlong WANG ; Chuan ZHAO ; Jincheng LIN ; Hongxing LIU ; Qiuhong ZENG ; Huadong CHEN ; Ye WANG ; Dapeng XU ; Wen CHEN ; Moping XU ; En ZHANG ; Da LIN ; Zhixiong LIN
Chinese Medical Journal 2024;137(7):859-870
Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.
2.Reflections on quarantine and supervision policies of imported experimental animals in Japan
Ning DING ; Jiaqi LIANG ; Hongkun FU ; Ying WANG ; Chunxia WANG ; Jiao REN ; Haiqiong YU ; Zhixiong LIN ; Lidan MA ; Daozhong ZHU ; Zhiqiang GAO ; Xiaowei WU ; Yufeng TAO
Chinese Journal of Comparative Medicine 2024;34(6):93-99
Japan is one of the main trading partners for the import and export of experimental animals in China,and its quarantine and supervision policies for the import and export of experimental animals are very detailed and strict.This article takes experimental dogs,cats,and monkeys as examples to provide an in-depth analysis of the quarantine and supervision policies for the main experimental animals exported to Japan.At the same time,it reflects on the current laws and regulations,import and export management method,standards,biosafety,breeding and management status,as well as the import and export business status of experimental animals in China.Suggestions are provided in improving the laws and regulations,import and export management method,ensuring national biosafety,improving the management level of experimental animal breeding,and promoting the import and export trade of experimental animals,in order to provide reference for comprehensively improving the production,use,and breeding management level of experimental animals in China and strengthening the trade between China and Japan.
3.Recent advance in papillary craniopharyngioma: from molecular biological characteristics to comprehensive treatment strategies
Ning LUO ; Yi LIN ; Tao HONG ; Zhixiong LIN
Chinese Journal of Neuromedicine 2024;23(10):1055-1063
In recent years, molecular biological research on papillary craniopharyngioma (PCP) has made significant breakthrough, leading to the clinical application of targeted therapy, which has yielded encouraging outcome. This article reviews the molecular biological characteristics of PCP, with a particular focus on mechanism of BRAF V600E gene mutation and its role in tumorigenesis. Furthermore, it also summarizes PCP comprehensive treatment strategies combining targeted therapy, surgery, and radiation therapy and proposes future research directions for precision PCP management, aiming at providing some references for clinical colleagues.
4.Cloning, identification and functional analysis of the goat transcription factor c-fos.
Tingting HU ; Yong WANG ; Dingshuang CHEN ; Chengsi GONG ; Yanyan LI ; Yan XIONG ; Jianmei WANG ; Zhixiong LI ; Yaqiu LIN
Chinese Journal of Biotechnology 2023;39(4):1684-1695
C-fos is a transcription factor that plays an important role in cell proliferation, differentiation and tumor formation. The aim of this study was to clone the goat c-fos gene, clarify its biological characteristics, and further reveal its regulatory role in the differentiation of goat subcutaneous adipocytes. We cloned the c-fos gene from subcutaneous adipose tissue of Jianzhou big-eared goats by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed its biological characteristics. Using real-time quantitative PCR (qPCR), we detected the expression of c-fos gene in the heart, liver, spleen, lung, kidney, subcutaneous fat, longissimus dorsi and subcutaneous adipocytes of goat upon induced differentiation for 0 h to 120 h. The goat overexpression vector pEGFP-c-fos was constructed and transfected into the subcutaneous preadipocytes for induced differentiation. The morphological changes of lipid droplet accumulation were observed by oil red O staining and bodipy staining. Furthermore, qPCR was used to test the relative mRNA level of the c-fos overexpression on adipogenic differentiation marker genes. The results showed that the cloned goat c-fos gene was 1 477 bp in length, in which the coding sequence was 1 143 bp, encoding a protein of 380 amino acids. Protein structure analysis showed that goat FOS protein has a basic leucine zipper structure, and subcellular localization prediction suggested that it was mainly distributed in the nucleus. The relative expression level of c-fos was higher in the subcutaneous adipose tissue of goats (P < 0.05), and the expression level of c-fos was significantly increased upon induced differentiation of subcutaneous preadipocyte for 48 h (P < 0.01). Overexpression of c-fos significantly inhibited the lipid droplets formation in goat subcutaneous adipocytes, significantly decreased the relative expression levels of the AP2 and C/EBPβ lipogenic marker genes (P < 0.01). Moreover, AP2 and C/EBPβ promoter are predicted to have multiple binding sites. In conclusion, the results indicated that c-fos gene was a negative regulatory factor of subcutaneous adipocyte differentiation in goats, and it might regulate the expression of AP2 and C/EBPβ gene expression.
Animals
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Goats/genetics*
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Cell Differentiation/genetics*
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Adipogenesis/genetics*
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Gene Expression Regulation
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Proteins/genetics*
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Cloning, Molecular
5.Design and implementation of quality management system for tumor radiotherapy
Shuirong YANG ; Xiaoyan YE ; Xiaobo LI ; Benhua XU ; Liyu TANG ; Zhixiong LIN
Chinese Journal of Radiation Oncology 2020;29(4):300-303
Objective:To design and implement a network-based quality management system for tumor radiotherapy.Methods:The system consists of B/S framework-based three-layer structures including the application layer, system service layer and data layer. It utilizes Nutz as the development framework to develop web applications, MySQL as the system database, Java programming language for system development, Tomcat as a system application server for project release and IE, Google and other mainstream browsers to achieve client access server functions.Results:The system can support integrated information management and service of quality control institutions at the provincial, municipal and county levels. The functions include procedure management, case management, quality control management, notification announcement, data management and system management, etc. The system has been set up and tested in the cooperation units, and the operation and function are in good condition.Conclusion:The system can support the assessment of online quality control, which is conducive to information analysis and sharing, promotes the standardization and normalization of quality control and improves work efficiency. Case management function can monitor the diagnosis and treatment processes of patients, establish continuous electronic record, deliver rational treatment and rehabilitation guidance plan, which play a pivotal role in the evaluation of tumor radiotherapy.
6.Discussion of the 8 th edition of AJCC/UICC staging system from the clinical stage Ⅲ nasopharyngeal carcinoma
Yingji HONG ; Mei LI ; Zhining YANG ; Yajie XUE ; Xiaoying GAO ; Zhixiong LIN
Chinese Journal of Radiation Oncology 2020;29(10):822-826
Objective:To evaluate the 8 th edition of AJCC/UICC staging system for stage Ⅲ nasopharyngeal carcinoma (NPC) by the survival analysis. All patients were treated with intensity-modulated radiotherapy (IMRT). Methods:Among 1351 treatment-na?ve NPC patients who received radiotherapy/chemoradiotherapy in our hospital from December 2008 to October 2014, 742 and 784 cases were classified as clinical stage Ⅲ based on the criteria of the 7 th and 8 th edition of AJCC/UICC staging systems, respectively. These patients were classified into three subgroups according to the 7 th and 8 th edition of AJCC/UICC staging systems: T 3N 0-1 as G 1( n=226, n=245), T 1-2N 2 as G 2( n=180, n=187) and T 3N 2 as G 3( n=336, n=352). The 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and local-regional recurrence-free survival (LRRFS) were analyzed with Kaplan- Meier method. The differences among different groups were evaluated by log-rank test. Results:There were 93.6% patients evaluated by the 8 th AJCC/UICC staging system remained the same cohort with those by the 7 th AJCC/UICC staging system. The 5-year OS, PFS, DMFS and LRRFS of the 8 th and 7 th staging systems were 84.8% and 85.4%, 76.2% and 77.0%, 80.4% and 81.3%, 89.8% and 90.6%, respectively (all P>0.05). The OS, PFS or DMFS significantly differed among three subgroups classified by the 8 th staging system (all P<0.001). In addition, statistical significance was observed between G 1 and G 2, and between G 1 and G 3(both P<0.05), whereas no statistical significance was noted between G 2 and G 3( P=0.183, 0.310, 0.248). Conclusions:The distribution features and clinical endpoints of clinical stage Ⅲ defined by the 8 th AJCC/UICC staging system are similar to those defined by the 7 th AJCC/UICC staging system. The distribution of survival risk significantly differs among different subgroups. N 2 plays a major role in assessing the survival risk of patients with stage Ⅲ NPC. In the era of IMRT plus chemotherapy, the effect of local tumors on clinical prognosis has been diminished. The 8 th AJCC/UICC staging system remains to be further improved.
7. Effect of 3D-CRT combined with PC chemotherapy on non-small cell lung cancer patients and serum CA125, TIMP-1, SAA levels and immune function
Yongcun WANG ; Wenhua HU ; Hualin CHEN ; Jiong LIN ; Zhennan LAI ; Yahai LIANG ; Aibing WU ; Zhixiong YANG
Journal of International Oncology 2019;46(11):662-667
Objective:
To investigate the effect of three-dimensional conformal radiotherapy (3D-CRT) combined with PC chemotherapy (paclitaxel + carboplatin) on non-small cell lung cancer (NSCLC) patients and the serum levels of CA125, tissue inhibitor of metalloproteinase-1 (TIMP-1), serum amyloid A (SAA) and T-lymphocyte subsets.
Methods:
A total of 100 patients with NSCLC treated in Affiliated Hospital of Guangdong Medical University from May 2015 to December 2017 were selected as the study subjects. They were divided into control group and observation group according to random number table method, with 50 cases in each group. The observation group was treated with 3D-CRT combined with PC chemotherapy, while the control group was treated with PC chemotherapy. The two groups were treated for 4 cycles. The therapeutic effect, serum CA125, TIMP-1, SAA, T-lymphocyte subsets and adverse reactions were compared between the two groups.
Results:
Four cases were lost to follow-up both in the two groups. The overall response rate in the observation group (43.48%, 20/46) was higher than that in the control group (23.91%, 11/46;
8.Investigation and research of physics technique and quality assurance for radiotherapy in east guangdong province
Xun PENG ; Baotian HUANG ; Zhihua LIU ; Xuanyi YU ; Qi KE ; Jingbin CHEN ; Dan OUYANG ; Tianbin MA ; Dongsheng GAO ; Zhixiong LIN ; Xiaowu DENG
Chinese Journal of Radiation Oncology 2018;27(4):343-347
Objective To investigate the physics technique and quality assurance (QA) during radiotherapy in the institutions from the East Guangdong province,aiming to provide reference for the construction of radiotherapy discipline and rational allocation of resources in the primary hospitals from the eastern Guangdong province.Methods From March 15 to May 20,2016,the general conditions,radiotherapy equipment,available technique and quality assurance (QA) in the medical institutions from eastern Guangdong were investigated and analyzed by online combined with on-spot surgery.Results There were 8 institutions which provided radiotherapy with 966 ward beds,a daily capacity of 632 patients and 222 radiotherapy practitioners.Radiotherapy equipment included 12 linear accelerators,5 after-loading devices,1γ-knife,8 CT simulators and 9 radiotherapy planning systems.Five institutions performed IMRT/VMAT,IGRT and ART.Dose verification was performed before precision radiotherapy delivery in all institutions except for 1 center.QA procedures were missing for the linear accelerators,CT simulators and after-loading devices.Short-term advanced studies and hand-by-hand teaching were the main approaches for staff professional training.Conclusions The resource allocation for radiotherapy in the medical centers from the eastern Guangdong province is scarce.The technique and QC levels greatly differ among different institutions.Standard QA protocols are urgently to be established and implemented.Extensive attentions should be paid to the the professional training for technicians.
9.Sleep architecture in drug naive patients with schizophrenia: A meta-analysis
Yun BIAN ; Weiye LIANG ; Weihua YUE ; Xiaole HAN ; Chen LIN ; Jing ZHANG ; Zhixiong WANG ; Botao MA
Chinese Mental Health Journal 2017;31(3):208-214
Objective:To assess the characteristics change of sleep architecture in drug naive patients with schizophrenia,compared with healthy control.Methods:The key words including schizophrenia and sleep architecture (or sleep structure or sleep disturbance or polysomnogram and so on) were used to search literatures in MEDLINE,Embase,Springer,PsychINFO,google scholar,Wanfang data,published from 1980 to 2015.Fifteen studies that compared sleep architecture in drug naive patients with schizophrenia and healthy control were included.Literature quality evaluation was performed with the Newcastle-Ottawa Scale.The meta-analysis was performed by using Stata13.0 software.Results:Compared to healthy control,the total sleep time decreased (P < 0.01),the sleep latency increased (P < 0.01),the sleep efficiency decreased (P < 0.01),and the rapid-eye-movemem (REM) sleep latency increased (P < 0.01) significantly in drug naive patients with schizophrenia.The proportion of stage1 was increased,and the proportions of stage4 and slow wave sleep stage were decreased,the differences between case and control were statistically significant.Conclusion:In the control of drug effects,patients with schizophrenia may have poorer sleep quality of be poorer than healthy controls,such as the decreased total sleep time,specifically slow wave sleep,prolonged sleep latency and decreased sleep efficiency.
10.Relation of radiotherapy dose and sternocleidomastoid muscle (SM) mass or late response in patients with nasopharyngeal carcinoma
Xuejin SANG ; Xiaoyan WANG ; Zhining YANG ; Baotian HUANG ; Zhixiong LIN
Chinese Journal of Radiation Oncology 2017;26(1):1-5
Objective To investigate the relationship of radiation dose with the volume and late toxicity of the sternocleidomastoid muscle ( SM) in patients with nasopharyngeal carcinoma. Methods SM was divided into upper part and lower part based on the lower edge of cricoid cartilage. Patients were divided into three groups according to the prescribed dose for clinical target volume at the lower neck ( CTV2 ) ( 0, 54,60 Gy) . The dosimetric parameters included Dmean , V66 , and V60 for the upper, lower, and whole SM. SM was delineated and the volume was calculated on computed tomography images in the treatment planning system before and at 6, 12, and 18 months after treatment. The anteroposterior and transversal diameters of SM at C3?C4 , C4?C5 , C5?C6 , and C6?C7 levels were measured and recorded. Late toxicity of neck skin and SM was evaluated according to the Common Terminology Criteria for Adverse Events V4 .0 criteria. Between?group comparison was made by t?test or Kruskal?Wallis non?parametric test. Between?group comparison of the sample rate was made by one?way analysis of variance. The correlation analysis was made by Spearman correlation. Results There were significant difference in SM volume between the three time points after treatment ( P=0. 000) . At 12 or 18 months after treatment, the volume of SM wasignificantly reduced ( P=0. 000,0. 000);the reduction in SM volume was significantly correlated with V66 of the SM and the upper SM ( P=0. 015,0. 020) . At 18 months after treatment, SM fibrosis was significantly correlated with V60 of the upper SM ( P=0. 030);the fibrosis of neck skin was significantly correlated with the Dmean and V60 of the upper SM ( P=0. 029,0. 005) . Conclusions In order to prevent the incidence of the fibrosis of neck skin and SM, the dose homogeneity should be as high as possible, while the number of hot spots should be as small as possible.

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