1.CD133+cells in combination with human umbilical cord stem cells in mouse heart failure
Mei HOU ; Hongxing ZHANG ; Qing YE ; Yong ZHANG
Chinese Journal of Tissue Engineering Research 2016;20(14):2066-2072
BACKGROUND:Currently, conventional treatment methods for heart failure are al ineffective. OBJECTIVE:To explore the combined effects of human umbilical cord stem cel s and CD133+cel s in mice with heart failure, providing a new insight into the treatment of heart failure. METHODS:Ful-term newborn umbilical cord from vaginal delivery was col ected to isolate CD133+cel s and human umbilical cord stem cel s using lymphocyte separation medium method. Twenty Balb/C nude mice were randomly subjected to mononuclear cel injection (mononuclear cel group) or injection of CD133+cel s combined with human umbilical cord stem cel s (combined group) via the tail vein after establishing heart failure models. RESULTS AND CONCLUSION:Fourteen days after injection, the body weight and liver, heart and lung mass of mice were significantly larger in the combined group than the mononuclear cel group (P<0.05). After 30 days, myocardial cel s arranged regularly in the combined group, but disorderly in the mononuclear cel group;compared with the mononuclear cel group, the average area of myocardial col agen fibers was significantly decreased in the combined group (P<0.05), and the level of serum matrix metal oproteinase-9 was also significantly lower in the combined group (P<0.05). Masson staining showed that blue-stained col agen fibers in the combined group were less but arranged neatly;however, in the mononuclear cel group, the number of col agen fibers that arranged irregularly was increased to different extents. To conclude, the combined use of CD133+cel s and human umbilical cord stem cel s has desired outcomes in the treatment of heart failure in mice, indicating a higher clinical value.
2.Expression of heat shock protein 27, 60 and 90 in gastric cancer and its clinical value
Zhandong ZHANG ; Wei YANG ; Fei MA ; Yonglei ZHANG ; Ermin MA ; Ye KONG ; Hongxing LIU ; Yawei HUA
Chinese Journal of Immunology 2016;32(7):1042-1049
Objective: To investigate the expression of HSP-27,-60 and -90 in gastric cancer and its clinical significance. Methods:66 cases of gastric carcinoma was detected by immunohistochemistry HSP-27,60 and 90 of the expression and clinical significance of combined with clinical and pathological characteristics, tumor cell proliferation and survival analysis of three kinds of heat shock protein expression. Results: HSP-27,-60 and -90 were highly expressed in gastric cancer tissues. HSP-27 expression and tumor size (pT,P=0. 026),organ metastasis (pM,P=0. 046) and pathological staging (P=0. 041),HSP-27 staining intensity and lymph node status were significantly correlated ( pN, P=0. 042 ) . HSP-60 expression was associated with gender ( P=0. 011),and HSP-60 staining intensity was associated with age (P=0. 027) and tumor grade (P=0. 031). There was no correlation between HSP-90 expression and the clinical pathological parameters of this study; however, the intensity of HSP-90 staining was significantly correlated with tumor size (P=0. 020,pT). Single factor analysis showed that HSP-90 was significantly associated with longer survival (P=0. 033). Multivariate analysis demonstrated that HSP-90 was highly expressed as an independent prognostic factor for gastric cancer (P=0. 026). Conclusion: the HSP-27,-60 and -90 and some clinical pathological parameters. These parameters is very important for the treatment of patients with gastric cancer. The high expression of HSP-90 in patients with gastric cancer were inde-pendent prognostic indicators.
3.Study on the construction and expression of the human 4-1BBL extracellular domain/anti-CD20 Fab' fusion protein.
Wenguo JIANG ; Dongsheng XIONG ; Fang LIU ; Hongxing GUO ; Ye SU ; Jingli LÜ ; Chunzheng YANG
Chinese Journal of Biotechnology 2008;24(3):376-380
Several studies have demonstrated the role of 4-1BBL in T cell activation. Furthermore, enhanced 4-1BB/4-1BBL interaction has been shown to amplify T-cell-mediated antitumor immunity in several mouse models. However, when applied in humans, it was difficult to generate sufficient T cells ex vivo and whole cell vaccines to transfer back into patients. To overcome this difficulty, we have focused on producing the human 4-1BBL extracellular domain/anti-CD20 Fab' fusion protein. In this report, PCR and overlap PCR were used to construct the human 4-1BBL extracellular domain/anti-CD20 Fab' expression vector. DNA sequence was analyzed by the Terminus of Dideoxy Nucleotide. The product was purified by affinity chromatography and analyzed by SDS-PAGE and HPLC; its antigen binding activity was examined by rosetting assay. The data of DNA sequence showed that the human 4-1BBL extracellular domain/anti-CD20 Fab' fusion protein was corrected. The fusion protein was recovered in high yield (up to 200 microg/mL) after E-taq purification. The fusion protein was capable of simultaneous binding to stimulated Jurkat cells and Raji cells as shown by cellular rosetting. In conclusion, the human 4-1BBL extracellular domain/anti-CD20 Fab' fusion protein was induced to express in E. coli 16C9. The results of some biological activity experiments indicated that the fusion protein could bind to stimulated Jurkat cells and Raji cells. Furthermore, 4-1BBL-negative tumors can be converted into 4-1BBL-positive tumors by the fusion protein without the need for 4-1BBL gene transfer to the malignant cells.
4-1BB Ligand
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biosynthesis
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genetics
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Antibodies, Bispecific
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immunology
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Antigens, CD20
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immunology
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Humans
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Immunoglobulin Fab Fragments
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biosynthesis
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genetics
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Immunotherapy
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methods
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Lymphoma, Non-Hodgkin
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therapy
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Recombinant Fusion Proteins
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biosynthesis
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genetics
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immunology
4.Efficacy of indine of composite Huaihua fructus posraleae combined with fractional CO2 laser on acral stable vitiligo
Haiyan CHEN ; Chunlei HAN ; Yanning YE ; Hongxing LI ; Guijun QIU
Chinese Journal of Primary Medicine and Pharmacy 2019;26(7):848-851
Objective To OvaluatO thO Officacy and safOty of indinO of compositO Huaihua fructus posralOaO combinOd with fractional CO2 lasOr on acral stablO vitiligo.Methods From OctobOr 2014 to August 2017, 79 casOs with acral stablO vitiligo in thO Sixth POoplO′s Hospital of Dongguan wOrO randomly dividOd into trOatmOnt group and control group according to thO digital tablO. ThO trOatmOnt group(51 casOs) was trOatOd with fractional CO2 lasOr onO timO a month for four timOs, and thO sOcond day was givOn topical indinO of compositO Huaihua fructus posralOaO twicO a day. ThO control group(28 casOs) was trOatOd with topical indinO of compositO Huaihua fructus posralOaO twicO a day. ThO trOatmOnt OffOct was obsOrvOd aftOr trOatmOnt for 3 months and 6 months. Results AftOr trOatmOnt for 3 months and 6 months, thO total OffOctivO ratOs of thO trOatmOnt group wOrO 39.22% , 62.75% ,rOspOctivOly, which wOrO significantly highOr than thosO of thO control group(32.14% , 42.86% ) (χ2 =12.557,18.021,all P<0.05). No sOrious advOrsO OvOnt was obsOrvOd in thO two groups.Conclusion IndinO of compositO Huaihua fructus posralOaO combinOd with fractional CO2 lasOr is safO and OffOctivO in thO trOatmOnt of stablO sporadic vitiligo.
5.Application of artificial intelligence in the target delineation of radiotherapy
Danfang YAN ; Lihong WANG ; Hongxing YE ; Senxiang YAN
Journal of International Oncology 2022;49(3):168-172
Artificial intelligence is the use of computer algorithms to copy or simulate human behavior, giving machines human-like ability. With the rapid development of radiotherapy technology, artificial intelligence has great potential value in all stages of radiotherapy. Image segmentation is the premise of target delineation using artificial intelligence. The commonly used methods in clinic mainly include automatic segmentation based on deep learning and atlas library. The technology of artificial intelligence in organs at risk delineation is relatively mature, which can significantly shorten the delineation time and improve the efficiency. The delineation of tumor targets has achieved some success, the accuracy still needs to be further improved. Artificial intelligence technology makes the target delineation more and more efficient, and the consistency and repeatability have been significantly improved. It is expected to provide more accurate and individualized treatment for patients.
6.The efficacy and safety of BCG in the prevention of postoperative recurrence of intermediate and high-risk non-muscle invasive bladder cancer: a randomized, controlled, multi-center clinical trial (mid-term report)
Hao YU ; Tianxin LIN ; Xiang LI ; Hailong HU ; Nan LIU ; Jian ZHANG ; Xudong YAO ; Zhaoyang WU ; Xiangbo KONG ; Liqun ZHOU ; Jiacun CHEN ; Wei LI ; Jinjian YANG ; Dongwen WANG ; Xiaodong ZHANG ; Youhan CAO ; Shaozhong WEI ; Ye TIAN ; Huiqing ZHANG ; Benkang SHI ; Zhanpo YANG ; Qingwen LI ; Jinkai SHAO ; Tie ZHONG ; Xiaolin WANG ; Hongxing HUANG ; Liming LI ; Jianhua TIAN ; Zhimin WANG ; Jin YANG ; Lin QI ; Jian HUANG
Chinese Journal of Urology 2019;40(7):485-491
Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1%.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P > 0.05).The 1-year recurrence-free survival rates were 80.0% in the group 1 and 88.3% in the group 2 and 73.7% in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95% CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 % CI 0.31-0.92,P =0.0266;95 % CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5% (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2% (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3% (32/222).The incidence of overall AE in the group 2 was 71.8% (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1% (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7% (26/223).The overall AE rate in the control group was 53.2% (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4% (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8% (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.
7.The efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation: a randomized, controlled, multi-center clinical trial with 2 years’ follow-up
Hao YU ; Kaiwen LI ; Hailong HU ; Xiang LI ; Nan LIU ; Jian ZHANG ; Xudong YAO ; Xiaodong ZHANG ; Wei LI ; Liqun ZHOU ; Xiangbo KONG ; Jinjian YANG ; Youhan CAO ; Junli WEI ; Jiacun CHEN ; Zhaoyang WU ; Dongwen WANG ; Xuhui ZHANG ; Jinkai SHAO ; Qingwen LI ; Huiqing ZHANG ; Xiaolin WANG ; Shaozhong WEI ; Ye TIAN ; Tie ZHONG ; Hongshun MA ; Kun LI ; Benkang SHI ; Jin YANG ; Yuhua QIAO ; Hongxing HUANG ; Liming LI ; Zhimin WANG ; Jianhua TIAN ; Tianxin LIN ; Jian HUANG
Chinese Journal of Urology 2020;41(10):724-730
Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.