1.Mechanism of glioma stem cells with high expression of PTPRZ1 inducing TAMs polarization to M2 immunosuppressive phenotype
Lele AN ; Ying YANG ; Qing LIU ; Feiyue DOU ; Lujing WANG ; Yue CHENG ; Chao WANG ; Qianying RUAN ; Lei ZHOU ; Haitao GUO ; Weikai KONG ; Xuegang LI ; Chuan LAN ; Fei LI ; Yu SHI
Journal of Army Medical University 2024;46(8):796-803
Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.
2.Prevalence of hypertension, blood pressure control and influencing factors in residents aged 35-75 years in Jiangsu Province
Haitao BI ; Jian SU ; Lulu CHEN ; Lan CUI ; Ran TAO ; Jinyi ZHOU ; Yu QIN
Chinese Journal of Epidemiology 2024;45(7):947-954
Objective:To understand the prevalence, blood pressure control, and influencing factors of hypertension in residents aged 35-75 years in Jiangsu Province, and provide data support and basis for hypertension prevention and treatment.Methods:A stratified cluster sampling method was adopted to conduct community population surveys in 22 districts and counties in 12 prefectures in Jiangsu from 2021 to 2022. A total of 123 531 permanent residents aged 35-75 years were included in the study. The questionnaire survey collected the information about the demographic characteristics, disease history, lifestyle, and control of hypertension of study subjects. Statistical software SPSS 23.0 was used for χ2 test and multivariate logistic regression analysis, and Joinpoint 4.9.1.0 software was used to evaluate the trend of age change. Results:The standardized prevalence of hypertension in study subjects was 46.60%, the prevalence was higher in men than in women, and in rural residents than in urban residents, and the standardized blood pressure control rate was 11.24%, and it was lower in men than in women and in rural residents than in urban residents. The hypertension prevalence and control rates showed increasing trends with age (both P<0.001). The multivariate analysis results showed that being man, older age, being rural resident, higher frequency of alcohol consumption, marital status of being separated and widowed, overweight and obese, abdominal obesity and stroke, diabetes mellitus and dyslipidaemic diseases histories, and family history of hypertension were risk factors for hypertension, and being man, being rural resident, living north area, higher frequency of alcohol consumption, and obesity were risk factors for blood pressure control. Conclusions:The prevalence of hypertension in residents aged 35-75 years in Jiangsu was high, and the rate of blood pressure control was low. It is suggested to take integrated intervention measures, especially in in rural residents and people with low levels of education to reduce the disease burden of the patients.
3.Chinese expert consensus on the management of immune-related adverse events of hepato-cellular carcinoma treated with immune checkpoint inhibitors (2021 edition)
Guoming SHI ; Xiaoyong HUANG ; Zhenggang REN ; Yi CHEN ; Leilei CHENG ; Shisuo DU ; Yi FANG ; Ningling GE ; Aimin LI ; Su LI ; Xiaomu LI ; Qian LU ; Pinxiang LU ; Jianfang SUN ; Hanping WANG ; Lai WEI ; Li XU ; Guohuan YANG ; Zhaochong ZENG ; Lan ZHANG ; Li ZHANG ; Haitao ZHAO ; Ling ZHAO ; Ming ZHAO ; Aiping ZHOU ; Rongle LIU ; Xinhui LIU ; Jiaming WU ; Ying ZHANG ; Jia FAN ; Jian ZHOU
Chinese Journal of Digestive Surgery 2021;20(12):1241-1258
The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.
4. Reduction of the atlantoaxial dislocation associated with basilar invagination through single-stage posterior approach: using Xuanwu occipital-cervical reduction surgical suite
Wanru DUAN ; Zhenlei LIU ; Jian GUAN ; Zhiyuan XIA ; Xinghua ZHAO ; Qiang JIAN ; Haitao LAN ; Zongmao ZHAO ; Fengzeng JIAN ; Zan CHEN
Chinese Journal of Surgery 2019;57(10):782-787
Objective:
To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital-cervical fusion system in single stage.
Methods:
Thirty-seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital, Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3±12.3) years (range: 18-69 years). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital-cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line, clivus-canal angle(CCA) and the length of syrinx were collected. The preoperative and postoperative JOA score and radiological measurements were compared by paired
5.Reduction of the atlantoaxial dislocation associated with basilar invagination through single?stage posterior approach: using Xuanwu occipital?cervical reduction surgical suite
Wanru DUAN ; Zhenlei LIU ; Jian GUAN ; Zhiyuan XIA ; Xinghua ZHAO ; Qiang JIAN ; Haitao LAN ; Zongmao ZHAO ; Fengzeng JIAN ; Zan CHEN
Chinese Journal of Surgery 2019;57(10):782-787
Objective To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital?cervical fusion system in single stage. Methods Thirty?seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital,Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3 ± 12.3)years (range: 18-69 years). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital?cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI),the distance of odontoid tip above Chamberlain line,clivus?canal angle(CCA) and the length of syrinx were collected. The preoperative and postoperative JOA score and radiological measurements were compared by paired t?test. Results The mean JOA score of the patients increased from 10.5 to 14.4 at the one?year follow?up(t=14.3,P=0.00).Complete reduction of AAD and BI was achieved in 34 patients.The mean clivus?canal angle improved from (118.0±6.5)degrees preoperative to (143.7±5.0)degrees postoperative(t=6.2,P=0.00).Shrinkage of the syrinx was observed 1 week after surgery in 24 patients,and 6 months in 31 patients.Twenty?eight patients achieved bone fusion 6 months after surgery. All the patients achieved bone fusion 12 months after surgery. One?side vertebral artery occlusion was diagnosed in 1 case postoperatively for transient dizziness,and relieved in 2 weeks.Two patients developed moderate neck pain after surgery, and relieved in 1 month. No implant failure, spacer subsidence or infection was observed. Conclusions The treatment of AAD associated with BI using Xuanwu occipital?cervical fusion system from posterior approach in single stage is effective and safe. Cage implantation intraarticularly and fixation with cantilever technique achieve complete reduction in most cases.
6.Reduction of the atlantoaxial dislocation associated with basilar invagination through single?stage posterior approach: using Xuanwu occipital?cervical reduction surgical suite
Wanru DUAN ; Zhenlei LIU ; Jian GUAN ; Zhiyuan XIA ; Xinghua ZHAO ; Qiang JIAN ; Haitao LAN ; Zongmao ZHAO ; Fengzeng JIAN ; Zan CHEN
Chinese Journal of Surgery 2019;57(10):782-787
Objective To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital?cervical fusion system in single stage. Methods Thirty?seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital,Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3 ± 12.3)years (range: 18-69 years). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital?cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI),the distance of odontoid tip above Chamberlain line,clivus?canal angle(CCA) and the length of syrinx were collected. The preoperative and postoperative JOA score and radiological measurements were compared by paired t?test. Results The mean JOA score of the patients increased from 10.5 to 14.4 at the one?year follow?up(t=14.3,P=0.00).Complete reduction of AAD and BI was achieved in 34 patients.The mean clivus?canal angle improved from (118.0±6.5)degrees preoperative to (143.7±5.0)degrees postoperative(t=6.2,P=0.00).Shrinkage of the syrinx was observed 1 week after surgery in 24 patients,and 6 months in 31 patients.Twenty?eight patients achieved bone fusion 6 months after surgery. All the patients achieved bone fusion 12 months after surgery. One?side vertebral artery occlusion was diagnosed in 1 case postoperatively for transient dizziness,and relieved in 2 weeks.Two patients developed moderate neck pain after surgery, and relieved in 1 month. No implant failure, spacer subsidence or infection was observed. Conclusions The treatment of AAD associated with BI using Xuanwu occipital?cervical fusion system from posterior approach in single stage is effective and safe. Cage implantation intraarticularly and fixation with cantilever technique achieve complete reduction in most cases.
7.Light-inducible CRISPR/Cas9 system for control of gene expression:research advances
Liting LAN ; Xiaoli WEI ; Haitao YAN ; Ruibin SU
Journal of International Pharmaceutical Research 2017;44(3):215-219
Cas9 is a RNA-guided double stranded DNA nuclease that participates in the CRISPR/Cas9 system. Wide-type Cas9 directly silences the expression of target gene by gene splicing. The engineered dCas9 protein with the mutation at D10A and H840A lacks the Cas9' s endonuclease function but keeps its DNA binding activity. dCas9 can activate special genes by fusing with transcription activator. Meanwhile,it can inhibit the gene transcription by directly binding to the target gene and stop gene transcrip?tion. Combination of light sensitive structures and CRISPR can produce light-inducible CRISPR/Cas9 system for control of gene expres?sion. This system is able to activate or inhibit gene expression via the use of controlling blue light(470 nm). In this review,we mainly discuss the development of the light inducible CRISPR/Cas9 system as well as its application in the control of gene expression.
8.Effects of saturated and unsaturated fatty acids on proliferation and autophagy of lung cancer cells
Huimin LI ; Jun WU ; Shang WU ; Huajun YU ; Yajun WANG ; Yuzhen XIONG ; Liubo LAN ; Haitao ZHANG
Medical Journal of Chinese People's Liberation Army 2017;42(8):668-673
Objective To investigate the effects of saturated fatty acids and unsaturated fatty acids on proliferation and autophagy of human lung cancer cells. Methods The lung cancer cells A549 were treated with stearic acid (saturated fatty acid) and doconexent (DHA, unsaturated fatty acid), respectively, in concentrations of 0, 30, 60, 120 and 240μmol/L. MTT test and cell clone formation assay were performed to detect the proliferation of A549 cells. The morphology of A549 autophagy was observed by confocal laser scanning microscopy after A549 cells were treated with stearic acid or DHA for 24 hours. Western blotting assay was used to detect the expression of autophagy-related protein after A549 cells were treated with stearic acid or DHA for 12, 24 and 36 hours, respectively. Results 30-240μmol/L stearic acid or DHA both inhibited the proliferation of A549 cells (P<0.05). Both stearic acid and DHA induced autophagy of A549 cells, meanwhile, down-regulated Phospho-mTOR (ser2481) and up-regulated LC3Ⅱ/LC3Ⅰ of A549 cells (P<0.05). Conclusions Both saturated fatty acid and unsaturated fatty acid can inhibit the proliferation and induce autophagy of lung cancer cells. The mechanisms of autophagy may be related to Phospho-mTOR (ser2481) signaling pathway.
9.Research progress of radiation-induced heart disease
Lan YU ; Haitao WAN ; Gang WANG ; Xiaotao ZHANG
Chinese Journal of Radiological Medicine and Protection 2016;36(6):475-480
Radiation therapy is one of the important comprehensive treatment strategies for thoracic neoplasms,but it also can cause radiation-induced heart disease (RIHD) which can affect the quality of life and even endanger the lives of patients while killing tumor.With the development of comprehensive treatment for cancer,the patients achieve better survival outcomes.And the study reported about RIHD increased as well,which made RIHD became an important complication of thoracic neoplasms' treatment.Though modem radiotherapy techniques and new therapeutic principles have significantly made the incidence of RIHD decreased,the harm of RIHD should not be ignored.In this article,we review the research progress of RIHD.
10.Effects of miR-424 on Proliferation and Migration Abilities in Non-small Cell Lung Cancer A549 Cells and Its Molecular Mechanism
LI HONGMIN ; LAN HAITAO ; ZHANG MING ; AN NING ; YU RUILIAN ; HE YANGKE ; GAN CHONGZHI
Chinese Journal of Lung Cancer 2016;19(9):571-576
Background and objectivehTe inhibitory ability of miR-424 on the proliferation of renal carcinoma cell and the migration and invasion of cancer cells has been widely explored and demonstrated. However, the effects of miR-424 on non-small cell lung cancer (NSCLC) have not been systematically examined. In this study, detected the growth and inva-sion effect of miR-424 in NSCLC A549 cell. hTe migration and molecular mechanism of this cell are also detected.Methods NSCLC A549 cell was transfected with miR-424 and its inhibitor. Atfer transfection, the proliferation ability of A549 cell was detectedby CCK8 assay. hTen, the migration ability in A549 cell was detected by migration assays. Furthermore, the expression level of MMP2 and MMP9 in A549 was detected by Western blot and immune lfuorescence. hTe 3'UTR of E2F6 was cloned into luciferase reporter vector and its enzymatic activitywas detected to verify whether miR-424 can target E2F6. hTe expres-sion level of E2F6 in a549 cell atfer transfecing with miR-424 was detected by Western blot.Results Atfer transfection of miR-424, the proliferation and migration abilities were remarkably decreased and the expression level of MMP-2 and MMP-9 were down-regulated in A549. Moreover, MiR-424 inhibited the enzymatic activity of luviferase reporter vector of E2F6. Spe-ciifcally, the expression level of E2F6 was down-regulated in A549.ConclusionmiR-424 can inhibit the proliferation and migration abilities of A549 by negatively regulating the expression of E2F6.

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