1.Prognostic value of chemotherapy-induced neutropenia in metastatic colon cancer patients undergoing first-line chemotherapy with FOLFOX
Yang CHEN ; Yanrong WANG ; Yan SHI ; Guanghai DAI
Journal of Peking University(Health Sciences) 2017;49(4):669-674
Objective: To evaluate the prognostic value of chemotherapy-induced neutropenia (CIN) in metastatic colon cancer undergoing first-line chemotherapy with FOLFOX.Methods: Data were collected from a retrospective survey of 158 consecutive metastatic colon cancer patients who had undergone FOLFOX chemotherapy.The clinicopathological characteristics and chemotherapy features of the patients were analyzed as potential prognostic factors.The patients were stratified by the decreased level of CIN to three groups: large decreased level (the number of neutrophil decreased more than 1.0×109 compared with that before chemotherapy),small decreased level (the number of neutrophil decreased less than 1.0×109 compared with that before chemotherapy) and the absence of neutropenia.Results: According to a multivariate COX model, decreased level of CIN was a independent prognostic factor of colon cancer patients.Hazard ratios of death were 0.687 (95% CI: 0.381-0.812, P=0.016) for patients with large decreased level of CIN and 0.817 (95% CI: 0.527-0.939,P=0.027) for those with small decreased level of CIN compared with those of absent neutropenia patients.Median overall survival was 12.9 months (95% CI: 10.4-15.4) for patients without neutropenia (A) compared with 20.8 months (95% CI: 18.3-23.1) for patients with large-decreased level of CIN (L) and with 17.3 months (95% CI: 16.2-18.8) for those with small-decreased level of CIN (S vs.L, P=0.018;L vs.A, P=0.009;S vs.A, P=0.011).Conclusion: Our results demonstrate that the decreased level of CIN is a predictor of prognosis in patients with metastatic colon cancer undergoing FOLFOX chemotherapy.Patients who have experienced large decreased level of CIN haave longer survival time than small decreased level of CIN or absent patients.To monitor CIN decreased level timely and adjust chemotherapy drug dose may help improve the prognosis.
2.An experimental study about how edaravone affect the nerve cells apoptosis in the compressed spinal cord
Bo GAO ; Mingyan DONG ; Xuyuan DING ; Yulin LIU ; Guoxi WANG ; Wenju FU ; Yang GUO ; Guanghai SUN
Journal of Chinese Physician 2017;19(4):514-517
Objective To investigate the protective function of edaravone in the compressed spinal cord.Methods There were 150 rabbits enrolled in each group in the experiment.Rabbits in both operation group and edaravone (EDA) treating group received mild spinal cord compressionby setting a flap head screw between C6 C7 after the neck.The spinal cord decompression was conducted seven days later.After 6 hours,rabbits in the EDA treating group were injected with a large amount of EDA through ear border veins,while the rabbits in the operation group only received 0.9% sodium chloride injection.The transmission electron microscope was used to observe the apoptotic bodies at 1 day,3 days and 7 days after compression,and 1 day,3 days,7 days,and 14 days after decompression.Flow cytometry was used to test the rate of apoptosis of spinal cord cells.Immunohistochemistry was used to test the expression of Bax protein that is related to apoptosis.Results The neuronal apoptosis appeared after compression in both operation group and EDA-treating group.The Basso Beattie Bresnahan (BBB) score,neuronal apoptosis rates,and Bax protein expressions in both groups were statistically different (P < 0.05) when the spinal cord was compressed in the first day and the third day,while there was no statistically different when spinal cord compressed at the seventh day (P > 0.05).After decompression of the spinal cord,the BBB score,neuronal apoptosis rates,and Bax protein expressions in both groups were becoming lower at the seventh day (P <0.05).Conclusions EDA has protective function for compressed spinal cord.However,only the compression of spinal cord compression period of sufficient decompression can fundamentally protect the spinal cord.
3.Analysis of risk factors of recurrent uveitis and establishment of prediction model
Jin, GONG ; Ping, WANG ; Guanghai, QIN ; Qingguo, YANG ; Ting, ZHAO ; Linling, WANG
Chinese Journal of Experimental Ophthalmology 2014;32(7):627-630
Background Replase of uveitis is a primary cause of vision damage.To predict recurrentassociated factors for uveitis is very critical for the prevention and management of uveitis.Objective This study was to explore the risk factors of recurrent uveitis and establish the prediction model of recurrent uveitis.Methods Clinical data of recurrent uveitis patients who were diagnosed in Renhe Hospital of Three Gorges University from July 1,2010 to June 30,2011 were retrospectively reviewed.The demography characteristics of the patients were collected and the disease was followed-up under the informed consent.Kaplan-Meier method was used to estimate the disease recurrence rate and to plot relapse-free survival curve at different levels of predictive factors.Multivariate Cox proportional hazards model was used to select independent risk factors of relapse and establish the prediction model for recurrent uveitis.Results Total 825 cases of recurrent uveitis were included and followed up for 1 month to 38 months,with a median following-up time of 16 months.Relapse of uveitis was identified in 149 cases (18.1%)during the following-up duration.The relapse-free survival time was from 1 month to 38 months,and the 1-,2-and 3-year cumulative recurrence-free survival rates were 87.3%,82.8% and 80.9%.Multivariate Cox proportional hazards regression analysis showed that immunosuppression withdrawal(X1) (β =0.940,Waldx2 =12.018,P =0.001),oral steroid withdrawal (X2) (β =1.334,Wald x2 =18.450,P < 0.001),colds (X3) (β =0.642,Wald x2 =11.988,P =0.001),work and study stress(X4) (β=0.285,Wald x2 =4.925,P=0.026) and excessive alcohol and tobacco(X5) (3--0.541,Wald x2 =4.718,P =0.030) were the independent risk factors for recurrence of uveitis.The risk of recurrence in patients with uveitis function model expression was h (t)=h0 exp (2.559 X1 +3.797 X2 + 1.901 X3 + 1.331 X4 +1.719 X5).Conclusions Replase of uveitis is an interaction of many factors,and immunosuppression withdrawal,oral steroid withdrawal,colds,work and study stress,excessive alcohol and tobacco are independent risk factors for recurrence of uveitis.An intervention according to the controllable factors is one of the important ways to prevent the recurrence of uveitis.
4.Gene expression profile of pulmonary tissues in different phases of lung ischemia-reperfusion injury in rats.
Jinsong, LI ; Jun, NIE ; Gang, CHEN ; Yongquan, GONG ; Ke, JIANG ; Guanghai, YANG ; Lei, LIU ; Jianjun, WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(5):564-70
In order to provide us new clues to induce some endogenous protective molecular mechanisms, the changes in gene expression profile induced by ischemia-reperfusion in pulmonary tissues of rats were investigated and the dynamic mechanism of pulmonary ischemia-reperfusion injury was elucidated. Thirty male Wistar rats were randomly divided into 6 groups: 5 ischemia-reperfusion (I/R) groups (I/R 0-h, I/R 1-h, I/R 3-h, I/R 6-h, I/R 24-h) and control group (n=5 in each). An in situ ischemia-reperfusion lung injury rat model was established by occluded hilus of lung. The RatRef-12 Expression Beadchip (22 226 gene probes per array) was used to analyze the pattern of gene expression in all groups. The results showed that 648, 340, 711, 1279 and 641 genes were differentially expressed in I/R 0-, 1-, 3-, 6-and 24-h groups respectively. The differentially expressed genes were classified as following 7 functional categories: cytokine, adhesion molecule, growth factor and apoptosis-related factor, oxidation and antioxidation molecule, metabolic enzyme, ion channel and aquaporin, signal transduction molecule. It was suggested that gene chip technology was an effective and quick method for screening differentially expressed genes. Many differentially expressed genes with different functions interacted each other to result in pulmonary ischemia-reperfusion injury.
Gene Expression Profiling
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Lung/*blood supply
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Random Allocation
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Rats, Wistar
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Reperfusion Injury/*genetics
5.Application of lipidomics in colorectal cancer
Guanghai TONG ; Yang TIAN ; Huaxing WU
Practical Oncology Journal 2019;33(2):179-182
Colorectal cancer is one of the most common malignant tumors in China. It poses a serious threat to health and its morbidity and mortality are increasing year by year. There are defects in early diagnostic markers and disease activity progression indi-cators for clinical applications. Lipidomics helps to analyze the etiology,pathological progression and clinical diagnosis of colorectal cancer by comparing differences in lipid metabolites in vivo,providing a new method and platform for research of colorectal cancer. This review is aimed at the application of lipidomics in colorectal cancer.
6.Altered microRNA Expression Profiles of Extracellular Vesicles in Nasal Mucus From Patients With Allergic Rhinitis.
Geping WU ; Guanghai YANG ; Ruxin ZHANG ; Guangyin XU ; Ling ZHANG ; Wu WEN ; Jianbing LU ; Jianyong LIU ; Yan YU
Allergy, Asthma & Immunology Research 2015;7(5):449-457
PURPOSE: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Exosomes or extracellular vesicles are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in allergic diseases. In this study, we characterized the microRNA (miRNA) content of exosomes in AR. METHODS: Extracellular vesicles were isolated from nasal mucus from healthy control subjects (n=10) and patients with severe AR (n=10). Vesicle RNA was analyzed by using a TaqMan microRNA assays Human Panel-Early Access kit (Applied Biosystems, Foster City, CA, USA) containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis for the differentially expressed miRNAs were performed using DIANA-mirPath. RESULTS: Twenty-one vesicle miRNAs were up-regulated and 14 miRNAs were under-regulated significantly (P<0.05) in nasal mucus from AR patients when compared to healthy controls. Bioinformatic analysis by DIANA-mirPath demonstrated that 32 KEGG biological processes were significantly enriched (P<0.05, FDR corrected) among differentially expressed vesicle miRNA signatures. Among them, the B-cell receptor signaling pathway (P=3.709E-09), the natural killer cell-mediated cytotoxicity (P=8.466E-05), the T-cell receptor signaling pathway (P=0.00075), the RIG-I-like receptor signaling pathway (P=0.00127), the Wnt signaling pathway (P=0.00130), endocytosis (P=0.00440), and salivary secretion (P=0.04660) were the most prominent pathways enriched in quantiles with differential vesicle miRNA patterns. Furthermore, miR-30-5p, miR-199b-3p, miR-874, miR-28-3p, miR-203, and miR-875-5p, involved in B-cell receptor and salivary secretion signaling pathways, were selected for validation using independent samples from 44 AR patients and 20 healthy controls. MiR-30-5p and miR-199b-3p were significantly increased in extracellular vesicles from nasal mucus when compared to healthy controls, while miR-874 and miR-28-3p were significantly down-regulated. In addition, miRNA-203 was significantly increased in AR patients, while miRNA-875-5p was found to be significantly decreased in AR patients. CONCLUSIONS: This study demonstrated that vesicle miRNA may be a regulator for the development of AR.
B-Lymphocytes
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Biological Processes
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Endocytosis
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Epithelial Cells
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Exosomes
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Humans
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MicroRNAs*
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Mucus*
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Receptors, Antigen, T-Cell
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Rhinitis*
;
RNA
;
Wnt Signaling Pathway
7.Role of HIF-induced EMT in invasion and metastasis of tumor.
Yang CHEN ; Yan SHI ; Guanghai DAI
Journal of Central South University(Medical Sciences) 2016;41(8):872-878
Hypoxia plays a vital role in tumor metabolism, proliferation, apoptosis, invasion and metastasis via hypoxia-inducible factor (HIF). Epithelial to mesenchymal transition (EMT) is a crucial process to metastasis, which could be triggered by hypoxia. EMT could be regulated by HIF via multiple pathways including TGF-β, Notch, and Wnt/β-catenin. It has been shown that anti-HIF drugs combined with anti-EMT therapies could be a promising strategy for tumor therapy.
Basic Helix-Loop-Helix Transcription Factors
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Epithelial-Mesenchymal Transition
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Humans
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Neoplasms
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Transforming Growth Factor beta
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beta Catenin
8.Gene Expression Profile of Pulmonary Tissues in Different Phases of Lung Ischemia-reperfusion Injury in Rats
Jinsong LI ; Jun NIE ; Gang CHEN ; Yongquan GONG ; Ke JIANG ; Guanghai YANG ; Lei LIU ; Jianjun WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(5):564-570
In order to provide us new clues to induce some endogenous protective molecular mechanisms, the changes in gene expression profile induced by ischemia-reperfusion in pulmonary tissues of rats were investigated and the dynamic mechanism of pulmonary ischemia-reperfusion in- jury was elucidated. Thirty male Wistar rats were randomly divided into 6 groups: 5 ische-mia-reperfusion (I/R) groups (I/R 0-h, I/R 1-h, I/R 3-h, I/R 6-h, I/R 24-h) and control group (n=5 ineach). An in situ ischemia-reperfusion lung injury rat model was established by occluded hilus of lung. The RatRef-12 Expression Beadchip (22 226 gene probes per array) was used to analyze the pattern of gene expression in all groups. The results showed that 648, 340, 711, 1279 and 641 genes were differentially expressed in I/R 0-, 1-, 3-, 6- and 24-h groups respectively. The differentially ex- pressed genes were classified as following 7 functional categories: cytokine, adhesion molecule, growth factor and apoptosis-related factor, oxidation and antioxidation molecule, metabolic enzyme, ion channel and aquaporin, signal transduction molecule. It was suggested that gene chip technology was an effective and quick method for screening differentially expressed genes. Many differentially expressed genes with different functions interacted each other to result in pulmonary ische- mia-reperfusion injury.
9.Clinical efficacy of preoperative SIB-IMRT for 26 cases of locally-advanced low rectal cancer
Qiteng LIU ; Linchun FENG ; Baoqing JIA ; Xiaohui DU ; Hongyi LIU ; Guanghai DAI ; Jing CHEN ; Yongqiang YANG ; Ke WEN ; Yunlai WANG ; Tao YANG ; Yuyan GAO
Chinese Journal of Radiation Oncology 2018;27(10):906-910
Objective To evaluate the feasibility and clinical efficacy of preoperative simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with neoadjuvant chemotherapy of capecitabine in patients with locally-advanced low rectal cancer.Methods Between 2015 and 2016,26 patients admitted to 301 Hospital who were diagnosed with locally-advanced low rectal cancer,which was located within 5 cm from the anal verge,were enrolled in this investigation.Dose fractionation pattern was delivered:58.75 Gy in 25 fractions (2.35 Gy/fraction) for rectal cancer and lymph node metastasis and 50 Gy in 25 fractions for the pelvic lymphatic drainage area and simultaneously combined with capecitabine chemotherapy (825 mg/m2,bid d 1-5 weekly).One cycle of capecitabine (1 250 mg/m2,twice daily,d 1-14)was given at one week after the completion of chemoradiotherapy (CRT).Total mesorectal excision (TME)was performed at 6 to 8 weeks after the completion of CRT.The primary endpoints included pathological complete response rate (ypCR) and sphincter-preserving rate.The secondary endpoints included acute toxicity,tumor downstaging rate and postoperative complications.Results Twenty-six patients successfully completed neoadjuvant CRT,25 of them underwent surgical resection and one patient failed to receive surgery due to pxrianal edema.Postoperative ypCR rate was 32% (8/25),the sphincter-preserving rate was 60% (15/25),the tumor downstaging rate was 92% (23/25) and the R0 resection rate was 100%.During the period of CRT,grade 1 and 2 adverse events occurred in 24 patients,grade 3 radiation dermatitis was noted in 2 cases.No ≥ grade 4 acute adverse event was observed.Postoperative complications included ureteral injury in one case and intestinal obstruction in one patient.Conclusions Preoperative SIB-IMRT combined with neoadjuvant chemotherapy of capecitabine is a feasible and safe treatment for patients with locallyadvanced low rectal cancer,which yields expected ypCR rate,R0 resection rate and sphincter-preserving rate.Nevertheless,the long-term clinical benefits remain to be elucidated.Clinical Trial Registry Chinese Clinical Trial Registry,registration number:ChiCTR-ONC-12002387.
10.Efficacy and complications of intravesical instillation of BCG for prevention of recurrence of moderate and high-risk non muscle invasive bladder cancer
Weibing SUN ; Zhiyu LIU ; Quanlin LI ; Xishuang SONG ; Xiangbo KONG ; Chunxi WANG ; Qifu ZHANG ; Qingguo ZHU ; Changfu LI ; Wanhai XU ; Guanghai YU ; Cheng ZHANG ; Jinyi YANG ; Tianjia SONG ; Jiye ZHAO ; Qizhong FU ; Lixin WANG ; Quanzhong DING ; Xuehui CAI ; Chuize KONG
Chinese Journal of Urology 2019;40(1):14-19
Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1%) cases,Ta in 20(18.9%) cases and carcinoma in situ in 6 (5.7%) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5%) patients experienced tumor recurrence and 2 (1.9%) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5%.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95%CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1% (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 %),9 cases (3.3 %) with economic reasons and 11 cases (4.0%) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.