1.Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and evolution.
Zhaoshi BAO ; Yongzhi WANG ; Qiangwei WANG ; Shengyu FANG ; Xia SHAN ; Jiguang WANG ; Tao JIANG
Frontiers of Medicine 2021;15(4):551-561
Glioma is the most common lethal tumor of the human brain. The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months. The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas. Unlike primary glioblastoma that usually develop de novo in the elderly, secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis. Based on various evolutional trajectories brought on by clonal and subclonal alterations, the evolution patterns of glioma vary according to different theories. Some important features distinguish the normal brain from other tissues, e.g., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrier, and others. The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer. Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment. However, the detailed reasons for the progression and recurrence of glioma remain controversial. In this review, we introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment and drug resistance, and their pre-clinical implements in clinical trials. This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.
Aged
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Brain Neoplasms/genetics*
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Drug Resistance
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Glioblastoma
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Glioma/genetics*
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Humans
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Mutation
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Neoplasm Recurrence, Local/drug therapy*
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Tumor Microenvironment
2.Retrospective analysis of pediatric kidney transplantation: a report of 244 cases
Huanxi ZHANG ; Jun LI ; Mingchuan HUANG ; Shenghui WU ; Qian FU ; Longshan LIU ; Ronghai DENG ; Chenglin WU ; Bowen XU ; Lizhong CHEN ; Jiang QIU ; Guodong CHEN ; Gang HUANG ; Jiguang FEI ; Suxiong DENG ; Changxi WANG
Chinese Journal of Organ Transplantation 2020;41(1):9-14
Objective:To explore the clinical characteristics and outcomes of pediatric kidney transplantations at a single center and discuss the related clinical issues.Methods:From January 1990 to October 2019, clinical data were analyzed retrospectively for 244 pediatric renal transplants. The youngest recipient was aged 1.8 years and the median age of pediatric recipients was 12.2 years. The major disease was primary or hereditary glomerulonephritis ( n=160, 69.0%), congenital anomalies of kidney and urinary tract (CAKUT), cystic renopathy and other hereditary nephropathies ( n=55, 23.7%). The donor sources included traditional deceased donor ( n=42, 17.2%), living-related donor ( n=19, 7.8%) and organ donation ( n=183, 75.0%). The median age of donors was 2 years (0-51) and the median weight 12.0(2.7-72.0) kg. From January 2013 to October 2019, 170 cases), the major induction immunosuppression regimen was anti-thymocyte globulin (ATG) ( n=110, 64.7%) or basiliximab ( n=58, 34.1%). The maintenance regimen was tacrolimus + mycophenolic acid (MPA) + glucocorticosteroids. Finally the outcomes and the complications were analyzed. Results:The survival rates of 244 kidney allograft recipients were 98.1%, 94.5% and 93.4% and the graft survival rates 92.6%, 84.2% and 82.0% at 1/3/5 years respectively. Ten recipients died of accident ( n=2, 20.0%), pneumonia after transplantation ( n=2, 20.0%) and intracranial hemorrhage ( n=2, 20.0%). Thirty-three recipients lost their allografts mainly due to intravascular thrombosis in graft ( n=5, 14.3%), acute rejection ( n=5, 14.3%) and death ( n=9, 25.7%). Besides, among 109 deceased donor allograft recipients, the postoperative outcomes were delayed graft function recovery (DGF) ( n=27, 24.8%), arterial thrombosis ( n=6, 5.5%), venous thrombosis ( n=1, 0.9%), graft perirenal hematoma ( n=6, 5.5%), raft artery stenosis ( n=10, 9.2%) and graft ureteral fistula ( n=1, 0.9%). The incidence of acute rejection was 17.5% and 23.2% at 1/3 year respectively. The recurrent rate of primary disease was 6.9%, including primary FSGS ( n=3, 42.9%) and IgA nephropathy ( n=2, 28.6%). At 1/3 year post-operation, the incidence of pulmonary infection was 16.9% and 22.4% and the incidence of urinary tract infection 26.9% and 31.7%. Excluding recipients with graft failure, the estimated glomerular filtration rate (eGFR) at 1/2/3 year postoperatively was (80.3±25.2), (81.4±27.8) and (71.8±27.6) ml/(min·1.73 m 2)respectively. Conclusions:The outcomes of pediatric renal transplantations are excellent at our center. Future efforts shall be devoted to optimizing the strategies of donor kidney selection and strengthening preoperative evaluations, perioperative and postoperative managements for improving the long-term outcomes of pediatric renal transplantations.
3. Clinicaland prognostic features of lipoprotein glomerulopathy in renal allografts
Jin ZHANG ; Xutao CHEN ; Gang HUANG ; Jiang QIU ; Guodong CHEN ; Lizhong CHEN ; Jiguang FEI ; Changxi WANG
Chinese Journal of Organ Transplantation 2019;40(10):620-623
Objective:
To explore the clinical and prognostic features of lipoprotein glomerulopathy (LPG) in renal allografts.
Methods:
Retrospective analysis was performed for two case of LPG in renal allografts. The onset time was 6 and 9 years after living transplantation respectively. Initial symptoms included proteinuria and hypoproteinemia. Color Doppler ultrasound showed an enlarged graft size and greater parenchymal echogenicity. One patient had hyperlipemia and elevated apolipoprotein E (ApoE). Methylprednisolone pulse was offered with an early control of hyperlipidaemia and proteinuria by fenofibrate and angiotensin-converting enzyme inhibitors (ACEIs). Yet it had no effect on graft function. The definite diagnosis was made by graft biopsy. Pathological examination indicated non-homogeneous lipid deposition in glomerular capillary, glomerular sclerosis, mesangial hypercellularity and tubular atrophy.
Results:
During a follow-up period of 8 and 10 years post-transplantation, two cases eventually lost their grafts within 2 and 1 year after biopsy respectively. With long-term dietary control and drug therapy, regular dialysis continued and both awaited a second transplantation.
Conclusions
LPG is generally steroid-resistant and refractory in renal allografts. And routine biopsy is recommended for patients with a high risk of occurrence. Early controls of hyperlipemia and hypoproteinemia and other risk factors should be also properly managed.
4. HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)-ide analog: new switch study
Peng HU ; Jia SHANG ; Wenhong ZHANG ; Guozhong GONG ; Yongguo LI ; Xinyue CHEN ; Jianning JIANG ; Qing XIE ; Xiaoguang DOU ; Yongtao SUN ; Yufang LI ; Yingxia LIU ; Guozhen LIU ; Dewen MA ; Xiaoling CHI ; Hong TANG ; Xiaoou LI ; Yao XIE ; Xiaoping CHEN ; Jiaji JIANG ; Ping ZHA ; Jinlin HOU ; Zhiliang GAO ; Huimin FAN ; Jiguang DING ; Dazhi ZHANG ; Hong REN
Chinese Journal of Hepatology 2018;26(10):756-764
Objective:
Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.
Methods:
Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (
5.Clinical analysis and outcome of 524 cases of kidney transplantation
Jun LIAO ; Qian FU ; Ronghai DENG ; Xiaopeng YUAN ; Jun LI ; Longshan LIU ; Chenglin WU ; Yitao ZHENG ; Huanxi ZHANG ; Suxiong DENG ; Jiguang FEI ; Jiang QIU ; Guodong CHEN ; Gang HUANG ; Lizhong CHEN ; Changxi WANG
Chinese Journal of Organ Transplantation 2018;39(8):470-474
Objective To explore the clinical outcome of renal transplantation and analyze the risk factors influencing the kidney allograft survival after transplantation.Methods The clinical data of 524 cases of renal transplantation between January 2007 and December 2015 were retrospectively analyzed.Serum creatinine was determined,and glomerular filtration rate(GFR) was estimated.The 1-,2-and 3-year patient and graft survival after transplantation was calculated.Adverse events were recorded.Results The median follow-up time was 17.2 months.The 1-,2-and 3-year graft survival rate after transplantation was 97%,95.8% and 95.3%,respectively.The 1-,2-and 3-year patient survival rate after transplantation was 97.8%,97% and 97%,respectively.The eGFR was (67.6 ± 24.1),(68.9±24.2) and (72.7 ± 26.2) ml·min-1 ·1.73 m-2 at 1st,2nd and 3rd year after transplantation.The incidence of delayed graft function(DGF) was 20.6% (108/524).Multivariate analysis revealed donor type (P =0.005) and the terminal creatinine (P<0.001) were the independent risk factors of DGF.Elder recipients (P =0.004),recipients with diabetes(P =0.031),preoperative positivity of panel reactive antibody(PRA) (P =0.023),and donor with hypertension (P =0.046) were risk factors influencing the kidney allograft survival.Conclusion Kidney transplantation showed good outcomes at 3rd year after transplantation.The recipient age,recipient's history of diabetes,preoperative PRA and donor's history of hypertension are independent risk factors for renal graft survival.
6.Retrospective analysis of schistosomiasis elimination history in Jingxi City, Guangxi Zhuang Autonomous Region
Shuilan YU ; Jiguang DENG ; Shaoren XU ; Zhihua JIANG
Chinese Journal of Schistosomiasis Control 2017;29(3):366-368
Objective To understand the schistosomiasis epidemic and control history in Jingxi City,so as to provide the ev-idence for improving the future work. Methods The data of schistosomiasis prevention and control work were collected and ana-lyzed comprehensively in Jingxi City from 1956-2015. Results From 1956,the schistosomiasis prevention and control work car-ried out,and in 1985,Jingxi City reached the standard of schistosomiasis transmission interrupted and no local schistosome in-fected residents and livestock were found for 36 years. In May 2016,the city reached the national standard of Schistosomiasis Elimination Assessment Review. The cumulative number of schistosomiasis detection of residents was 348801 person-times, and 10434 schistosomiasis patients were found. The cumulative number of schistosomiasis detection of cattle was 20674 head-times,and 590 schistosome infected cattle were found. The cumulative schistosomiasis treatment number of residents was 18739 per-son-times,and 512 cattle were treated. The cumulative detection area with Oncomelania hupensis was 65213.25 hm2 ,and 353.80 hm2 area with O. hupensis snails was found. Conclusions Jingxi City has reached the standard of schistosomiasis elimi-nation,but there is still recurrence of O. hupensis snails,and the imported infection source exists. Therefore,we should strength-en the monitoring of floating population.
7.Antibody monitoring and graft biopsy after renal transplantation contribute to early diagnosis of antibody mediated rejection
Qian FU ; Changxi WANG ; Jun LI ; Runjun HE ; Longshan LIU ; Suxiong DENG ; Jiguang FEI ; Jiang QIU ; Guodong CHEN ; Gang HUANG ; Lizhong CHEN
Organ Transplantation 2016;7(6):433-437
Objective To analyze the necessity of anti-human leukocyte antigen (HLA)antibody monitoring and graft biopsy on early diagnosis of antibody-mediated rejection (AMR). Methods Fifty-one recipients with de novo donor specific antibody (dnDSA)were screened and chosen. Donor specific antibody (DSA)and its ability to bind with C1 q were evaluated. Pathological biopsy of the kidney graft was performed. The recipients diagnosed with AMR were divided into the unstable and stable kidney function groups. Type of DSA,binding ability of the complement and Banff score were statistically compared between two groups. Kaplan-Meier survival analysis of the kidney graft in the recipients from non-rejection, unstable and stable kidney function groups was performed. Results Type of HLA antibody,mean fluorescent intensity (MFI)of DSA,C1 q binding ability and C4d deposition in peritubular capillary did not significantly differ between the unstable and stable groups (all P>0. 05 ). Histomorphologically,the Banff score of microvasculitis,endarteritis,renal tubule-interstitial nephritis,transplantation glomerulopathy and renal tubular atrophy-stroma fibrosis did not significantly differ between two groups (all P>0. 05 ). In the unstable group,the accumulated survival rate of the kidney graft was significantly lower compared with that in the stable group,which was significantly lower than that of their counterparts who were ineligible for pathological diagnosis (P=0. 002). Conclusions It is necessary to perform regular anti-HLA antibody monitoring and pathological puncture examination after renal transplantation,which contributes to early detection and diagnosis of AMR.
8.Related research of male breast cancer and CAG repeat polymorphism of AR gene
Jialin CUI ; Rui HUANG ; Yongdong JIANG ; Jiguang HAN ; Ming NIU ; Wei WEI ; Wei ZHENG ; Yanni SONG
Practical Oncology Journal 2015;(6):492-496
Objectiv e To investigate the correlation between ( CAG) n repeat polymorphism of androgen receptor(AR)geneandmalebreastcancer.Methods 40casesofmalebreastcancerand40controlswerecol-lected.DNA was extracted from peripheral blood and the AR gene CAG coding exon sequences for PCR amplifica -tion,sequencing and calculated the number of CAG repeats frquency .χ2 test and Logistic regression analysis were used assess the AR gene CAG repeat length frequency affect the number of male breast cancer risk .Results There was statistically significant difference in male breast cancer cases and controls the number of CAG repeat length frequency.Man for whom the(CAG)n≥22 repeat sequence had 3.52 times risk of male breast compared (CAG)n≤22(OR=3.52,P=0.036).Conclusion AR gene CAG repeat length is a predictor of the frequency of male breast cancer risk .Longer CAG repeats can increase the risk of male breast cancer .
9.Percutaneous antegrade ureteral stent in the treatment of renal graft ureteral obstruction: 11eases report
Honggang QI ; Jiangyong LOU ; Yu REN ; Wenbo GAO ; Shuwei ZHANG ; Jiguang JIANG ; Guobin WENG ; Xuping YAO
Chinese Journal of Organ Transplantation 2012;33(5):299-302
ObjectiveTo explore the efficacy and safety of percutaneous antegrade stenting in the treatment of ureteral obstruction after renal transplantation.MethodsWe retrospectively reviewed 11patients with renal graft ureteral obstruction (2 cases of acute obstruction and 9 cases of chronic obstruction) from March 2009 to March 2011.The etiology of the obstruction was renal graft-ureter-bladder anastomotic stricture in 5 cases,stone obstruction in 2 cases,and undetermined in 4 cases.Renal graft and collecting system were examined by ultrasonography preoperatively to select suitable puncture position,and then ureteropyelography was performed under X-ray guidance.When the obstruction location was clear,the urology guidewire was implanted to the bladder by needle,and then guidewire was released by cystoscopy.Ureteral stent was implanted along the guidewire,and upper ureteral stents was observed under X-ray. After removal of guidewire,the stent location was confirmed once again.The renal pelvis fistula drainage lasted for 1-2 weeks,and ureteral stent to 6 months to one year.Ultrasound and renal function were tested after 1week,1month,3 months and 6 months,and then every six months.ResultsOperation was done successfully in 10 patients,and failed in one case due to a long segment of ureteral stenosis.The operating time of ureteral stent implantation was 54±27 min.Serum creatinine of patients was reduced from preoperative 326±147 to postoperative 89±49 μmol/L.During a follow-up period of 6 to 27 months,no complications occurred.ConclusionPercutaneous antegrade stenting in the treatment of ureteral obstruction after renal transplantation is safe and effective.
10.Alleviative effects of green tea polyphenols on cyclosporine A-induced inhibition of vasorelaxation
Wenbo GAO ; Xuping YAO ; Jiguang JIANG
Chinese Journal of Tissue Engineering Research 2011;15(44):8277-8280
BACKGROUND: Vasorelaxation plays an important role In the occurrence of cyclosporine A (CsA)-induced nephrotoxlcity.OBJECTIVE: To observe the alleviative effects of green tea polyphenols (GTP) on CsA-induced inhibition of vasorelaxation and the underlying mechanisms.METHODS: Sprague-Dawley rats were randomly and evenly divided into four groups: CsA, control, CsA + GTP, and GTP. After 5 weeks of drug treatment, blood urea nitrogen (BUN) and creatinine (Cre) levels were determined. Then the thoracic aorta rings were mounted on a bath system, and acetylcholine was used to induce vasorelaxation. The effects of L-NAME and indomethacin and the denuded vasorelaxation were evaluated.RESULTS AND CONCLUSION: The BUN and Cre levels in the CsA group were significantly higher than those in the control group (P < 0.05). The maximal response (Emax%) for acetylcholine-induced vasorelaxation in the CsA group was significantly lower than that in the control and GTP groups. After pretreatment with L-NAME, vasorelaxation was significantly lower in the CsA,CsA+GTP and GTP groups than in the control group. After pretreatment with indomethacin, vasorelaxation was significantly higher in the control, CsA +GTP, and GTP groups than in the CsA group. The level of nitric oxide metabolites in the vascular tissue in the CsA group was significantly lower compared with other groups. The results demonstrated that CsA can decrease nitric oxide levels in vascular tissues and induce abnormal endothelium-dependent vasorelaxation, which is mediated by nitric oxide pathway.

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