1.Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses
Zhiqiang GAO ; Jie LIN ; Peng HONG ; Zaihong HU ; Junjun DONG ; Qinlin SHI ; Xiaomao TIAN ; Feng LIU ; Guanghui WEI
Journal of Southern Medical University 2024;44(4):727-738
Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.
2.Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses
Zhiqiang GAO ; Jie LIN ; Peng HONG ; Zaihong HU ; Junjun DONG ; Qinlin SHI ; Xiaomao TIAN ; Feng LIU ; Guanghui WEI
Journal of Southern Medical University 2024;44(4):727-738
Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.
4. The preliminary report of a registration clinical trial of proton and heavy ion irradiation
Jiade LU ; Ming YE ; Xiaomao GUO ; Shen FU ; F. Michael MOYERS ; Qing ZHANG ; Jingfang MAO ; Lin KONG ; Wen Chien HSI ; Kambiz SHAHNAZI ; Jingfang ZHAO ; Zhen ZHANG ; Xiumei MA ; Songtao LAI ; Xiaomeng ZHANG ; Ningyi MA ; Yunsheng GAO ; Xin CAI ; Xiyin GUAN ; Junhua ZHANG ; Bin WU ; Jingyi CHENG ; Yin-xiang-zi SHENG ; Wei REN ; Jun ZHAO ; Lining SUN ; Guoliang JIANG
Chinese Journal of Oncology 2018;40(1):52-56
Objective:
To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation.
Methods:
Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation.
Results:
Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed.
Conclusions
IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.
5.The preliminary report of a registration clinical trial of proton and heavy ion irradiation
Jiade LU ; Ming YE ; Xiaomao GUO ; Shen FU ; F.Michae MOYERS ; Qing ZHANG ; Jingfang MAO ; Lin KONG ; Chien Wen HSI ; Kambiz SHAHNAZI ; Jingfang ZHAO ; Zhen ZHANG ; Xiumei MA ; Songtao LAI ; Xiaomeng ZHANG ; Ningyi MA ; Yunsheng GAO ; Xin CAI ; Xiyin GUAN ; Junhua ZHANG ; Bin WU ; Jingyi CHENG ; Yin?xiang?zi SHENG ; Wei REN ; Jun ZHAO ; Lining SUN ; Guoliang JIANG
Chinese Journal of Oncology 2018;40(1):52-56
Objective To verify the safety and efficacy of IONTRIS particle therapy system ( IONTRIS) in clinical implementation. Methods Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial:31 males and 4 females with a median age of 69 yrs ( range 39?80) . Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non?metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results Twenty?two patients received carbon ion and 13 had proton irradiation. With a median follow?up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression?free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological?recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty?five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow?up. Six ( 17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow?up is needed to observe the late toxicity and long term result.
6.The preliminary report of a registration clinical trial of proton and heavy ion irradiation
Jiade LU ; Ming YE ; Xiaomao GUO ; Shen FU ; F.Michae MOYERS ; Qing ZHANG ; Jingfang MAO ; Lin KONG ; Chien Wen HSI ; Kambiz SHAHNAZI ; Jingfang ZHAO ; Zhen ZHANG ; Xiumei MA ; Songtao LAI ; Xiaomeng ZHANG ; Ningyi MA ; Yunsheng GAO ; Xin CAI ; Xiyin GUAN ; Junhua ZHANG ; Bin WU ; Jingyi CHENG ; Yin?xiang?zi SHENG ; Wei REN ; Jun ZHAO ; Lining SUN ; Guoliang JIANG
Chinese Journal of Oncology 2018;40(1):52-56
Objective To verify the safety and efficacy of IONTRIS particle therapy system ( IONTRIS) in clinical implementation. Methods Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial:31 males and 4 females with a median age of 69 yrs ( range 39?80) . Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non?metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results Twenty?two patients received carbon ion and 13 had proton irradiation. With a median follow?up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression?free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological?recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty?five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow?up. Six ( 17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow?up is needed to observe the late toxicity and long term result.
7.Prevent effects of ex vivo oxygenated blood continuous perfusion on donor-lung injury
Xiaomao LONG ; Xiangwei LI ; Hui LIN ; Yifan ZHOU
Chinese Journal of Organ Transplantation 2013;(5):294-298
Objective To study the protective effect of normothermic ex vivo perfusion to prevent donor-lung injury.Method After being flushed with perfadex solution through the pulmonary artery and vein,the donor lungs were divided to control group (preserved with 4℃ cold static preservation,n =8) and experimental group (preserved with ex vivo oxygenated blood continuous perfusion,n =8).Pulmonary function indexes,including pulmonary vascular resistance (PVR),lung ventilation resistance(LVR),the left inferior pulmonary vein(LIPV) blood PO2,and lung water content,were evaluated.Lung injury were studied by light microscopic observation and detecting the expression of proimflammatory factor IL-1β was detected.Result (1) Lung function evaluation:in both group,PVR,LVR and lung water content gradually increased,LIPV PO2 gradually declined;But in the same time point PVR and LVR in group were were significantly less than in control group (P<0.05),LIPV PO2 in experimental group were were significantly more than in control group(P<0.05).(2)Lung injury evaluation:Lung tissue edema classification in both group were significantly higher than in normal lung(P<0.05),but classification in experimental group were significantly lower than in control group(P<0.05).The expression of IL-1β in experimental group (0.422 ± 0.132) were significantly lower than in control group(0.578 ± 0.163,P<0.05).Conclusion Ex vivo oxygenated blood continuous perfusion without ventilator is a feasible technique for lung preservation.It ameliorates hypothermic time-dependent ischemic injury.But further systems evaluation in complete physiologic condition is necessary.
8.The effect of heart valve replacement in the same period of radiofrequency ablation on atrial fibrillation
Xiangwei LI ; Xiaomao LONG ; Hui LIN ; Shengjing LIANG ; Yifan ZHOU ; Weijun LU
Clinical Medicine of China 2013;29(11):1156-1158
Objective To investigate the effectiveness of heart valve replacement in the same period of radiofrequency ablation in the treatment of atrial fibrillation.Methods Eighty-six patients with atrial fibrillation underwent heart valve replacement in the same period of bipolar radiofrequency ablation system according to the maze heart valve replacement operation principle.And optimized the operation method.Results No death occurred during operation.The average ablation time was (23 ± 8) minutes with a range of 16-56 minutes.Sinus rhythm of the heart was restored after surgery in all patients (100%).The long-term success rate was 98.8% (85/86).Conclusion Our optimization of heart valve replacement in the same period of radiofrequency ablation enhanced the success rate of the operation,simplified the procedures,meanwhile it might need widely application clinically.
9.A study of the positioning errors of head and neck in the process of intensity modulation radiated therapy of nasopharyngeal carcinoma
Chengguang LIN ; Liuwen LIN ; Bingti LIU ; Xiaomao LIU ; Guowen LI
Chinese Journal of Radiation Oncology 2011;20(4):322-325
Objective To investigate the positioning errors of head and neck during intensity-modulated radiation therapy of nasopharyngeal carcinoma.Methods Nineteen patients with middle-advanced nasopharyngeal carcinoma (T2-4N1-3M0), treated by intensity-modulated radiation therapy, underwent repeated CT during their 6-week treatment course.All the patients were immobilized by head-neck-shoulder thermoplastic mask.We evaluated their anatomic landmark coordinated in a total of 66 repeated CT data sets and respective x, y, z shifts relative to their position in the planning CT.ResultsThe positioning error of the neck was 2.44 mm±2.24 mm,2.05 mm±1.42 mm,1.83 mm±1.53 mm in x, y, z respectively.And that of the head was 1.05 mm±0.87 mm,1.23 mm±1.05 mm,1.17 mm±1.55 mm respectively.The positioning error between neck and head have respectively statistical difference (t=-6.58,-5.28,-3.42,P=0.000,0.000,0.001).The system error of the neck was 2.33,1.67 and 1.56 higher than that of the head, respectively in left-right, vertical and head-foot directions;and the random error of neck was 2.57,1.34 and 0.99 higher than that of head respectively.Conclusions In the process of the intensity-modulated radiation therapy of nasopharyngeal carcinoma, with the immobilization by head-neck-shoulder thermoplastic mask, the positioning error of neck is higher than that of head.
10.Comparative study of three recruitment maneuvers in acute respiratory distress syndrome caused by extrapulmonary disease
Huiju BU ; Haiyang WEN ; Cun WANG ; Xiaomao LIN ; Liang CHEN
Chinese Journal of Postgraduates of Medicine 2010;33(18):1-3
Objective To evaluate the effects and side effects of three different recruitment maneuvers (RM) in acute respiratory distress syndrome (ARDS) caused by extrapulmonary disease.Methods Forty-four patients of extrapulmonary ARDS, according to crossover design methods, were undergone three RM in different periods, including sustained inflation (SI), increase progressively positive end expiratory pressure (IP), pressure control ventilation (PCV). Heart rate (HR), mean arterial blood pressure (MAP), central venous pressure (CVP), oxygenation index, lung compliance were recorded before and after RM, and were analyzed for statistical analysis. Results Oxygenation index and lung compliance were increased obviously in a short time after RM, improvement of IP method were better more obviously than the other two methods [1 h oxygenation index after RM:227 ± 42 vs 190 ± 19,186 ± 21; lung compliance:(59.4±12.5 ) ml/cm H2O(1 cm H2O = 0.098 kPa) vs (50.1 ± 9.3 ), (49.7 ± 10.6) ml/cm H2O;P< 0.05], 2h after RM,there were no statistical difference among the three methods (P>0.05). After RM,HR and CVPwere increased, MAP was decreased in a short time, changes of SI method were smaller than the other two inethods [10 min HR after RM: (94.0±10.3 ) beats/min vs (116.0 ± 14.8 ), ( 107.0 ± 5.7 ) beats/min; CVP:(13.7±3.1 )cm H2O vs ( 18.4 ± 6.7 ), ( 15.4 ± 2.7 )cm H2O; MAP: ( 87.0 ± 12.1 ) mm Hg( 1 mm Hg = 0.133 kPa) vs (73.0 ± 4.8), (81.0 ± 6.6) mm Hg;P< 0.05), 20 min after RM, there were no statistical difference among the three methods (P> 0.05). Conclusion When extrapulmonary ARDS undergo RM ,IP method is the most effective on increasing oxygenation index and lung compliance, SI method has the smallest side effect on hemodynamics.

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