1.Research progress on the role of oxidative stress in ischemia-reperfusion injury of marginal donor liver transplantation
Weidong GAO ; Longlong YANG ; Qingchen YIN
Organ Transplantation 2022;13(1):126-
Common marginal donor liver mainly consists of fatty donor liver, elderly donor liver, small volume donor liver and liver graft from donation after cardiac death (DCD), etc. The application of marginal donor liver may resolve the severe shortage of donor liver to certain extent. Nevertheless, marginal donor liver yields a higher risk of ischemia-reperfusion injury (IRI) and causes more severe IRI than normal donor liver, which is a main cause for the failure of transplantation. In addition, oxidative stress is a major risk factor causing IRI of marginal donor liver. Therefore, how to mitigate oxidative stress and alleviate IRI of marginal donor liver has become a hot spot in clinical practice. Reactive oxygen species (ROS)-mediated oxidative stress occurs throughout the whole process of IRI. In this article, the role of oxidative stress in IRI of marginal donor liver transplantation and the ROS-targeted prevention and treatment were reviewed, aiming to provide reference for clinical practice.
2.Influence of extracorporeal photochemotherapy-treated regulatory dendritic cells on T cell proliferation
Guosheng DU ; Shaozhen YANG ; Yuxiang WEI ; Longlong SUO ; Likui FENG ; Jiyong SONG ; Zhidong ZHU
Medical Journal of Chinese People's Liberation Army 2017;42(8):698-701
Objective To investigate the effect of regulatory dendritic cells treated by extracorporeal photochemotherapy on T cell proliferation. Methods Human peripheral blood mononuclear cells (PBMCs) were obtained and the immature dendritic cells (imDCs) were induced by recombinant human granulocyte and macrophage colony stimulating factors. SPDCs were obtained by PUVA treatment, and ECDCs were co-cultured with imDCs and PUVA-SP to obtain immunoprecipitated dendritic cells. In vitro, imDCs were co-cultured with SPDCs to obtain SPDCs; imDCs were added to 10ng/ml of LPS, and cultured for 1 day to obtain DCs. The expressions of CD11c, CD83 and CD86 on the surface of the cells were detected. The effect of imDCs on the proliferation of recipient T cells was detected by mixed lymphocyte culture method. Results The early apoptosis rate of PUVA-treated cells was 91.33%. The positive expression rates of CD83 and CD86 in ecpDCs were 22.83%±5.26% and 22.06%±4.37%, respectively, which were similar to those of imDCs (15.06%±0.59%, 15.19%±1.83% (P<0.01), but significantly lower than those in DCs (99.79%±0.36%, 99.85%±0.19%, respectively), the difference was statistically significant (P<0.01). The recipient imDC cells phagocyting the appoptotic splenic lymphocytes from the donor significantly inhibited the proliferation of recipient T cells. Conclusion Apoptosis of splenic lymphocytes induced by extracorporeal photochemotherapy can inhibit the maturation of dendritic cells and inhibit the proliferation of T lymphocytes.
3.Clinical study of transperitoneal and retroperitoneal robot-assisted partial nephrectomy for renal hilar tumors
Jianlin YUAN ; Ping MENG ; Xiaojian YANG ; Yanzhu WANG ; Weijun QIN ; Yuntao ZHANG ; Longlong ZHANG ; Bo YANG ; Peng WU ; Yuming JING ; Wanxiang ZHENG
Chinese Journal of Urology 2017;38(7):502-506
Objective To investigate the clinical value and experience of transperitoneal and retroperitoneal robot-assisted partial nephrectomy for renal hi1 ar tumors.Methods We evaluated 48 patients who had partial nephrectomy for renal hilar tumor by robotic surgical syestem from January 2013 to March 2017.In those cases,35 were male and 13 were female,with an average age of 57.3 (range from 41 to 75 ),27 cases were ventral tumor and 21 cases were dorsal tumor.3 cases were totally confined to the renal parenchyma,the other 45 cases were partially confined to the renal parenchyma.18 cases were performed surgery by retroperitoneal route,the rest 30 cases were performed by peritoneal route.Results A total of 48 patients underwent successful robotic partial nephrectomy for renal hilar tumors.The mean warm ischemia time was 22 minutes (range from 16 to 33 minutes) and the mean estimated blood loss was 88 md (range from 50 to 350 ml).No bleeding-related complications were found.Histopathology confirmed 39 cases of ccRCC,7 cases of angioleiomyolipoma,2 cases of renal oncocytoma.There was one case in this review was positive surgical margin (2.1%) and found no sign of recurrence during the short term post-operation follow-up.All cases in this review are following up after surgery to date from 2 months to 4 years,no cases of tumor recurrence or metastasis were found.Conclusions The application of transperitoneal and retroperitoneal RAPN is the effective and safe way for renal hilar tumor resection,and it has a clear advantage of renal surgical incision stitching and tumor complete resection.The choice of surgical approaches depends on the size and location of tumor and the clinical experience of the surgeon.
4.Correlation of tumor recurrence after liver transplantation for hepatocellular carcinoma with the expression ;levels of regulatory T cells and cytokines in peripheral blood
Shaozhen YANG ; Lin ZHOU ; Guosheng DU ; Jiyong SONG ; Zhidong ZHU ; Likui FENG ; Longlong SUO ; Yonggen ZHENG
Organ Transplantation 2016;7(5):382-385
Objective To analyze the correlation of tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC)with the expression levels of regulatory T cell (Treg)and cytokines in peripheral blood. Methods A total of 56 patients who underwent liver transplantation in the 309th Hospital of People's Liberation Army from 2010 to 2014 were studied. According to the postoperative pathological data,all the patients were divided into the group of liver transplantation for HCC (HCC group,n=28)and group of liver transplantation for cirrhosis (liver cirrhosis group,n=28), of which the HCC group was further divided into non-recurrence group (n=8)and recurrence group (n=20)according to the situation of postoperative tumor recurrence. The expression levels of Treg and cytokines [vascular endothelial growth factor (VEGF),interleukin (IL)-2,IL-10,IL-12,transformation growth factor (TGF)-βand interferon (IFN)-γ]in peripheral blood of the patients in various groups were compared. Results Compared with the liver cirrhosis group,levels of IFN-γand IL-12 in the non-recurrence group increased significantly (both P<0.05);levels of Treg%,VEGF,IFN-γ, IL-10 and TGF-βin the recurrence group increased significantly,while levels of IL-2 and IL-12 decreased significantly (all P<0.05). Compared with the non-recurrence group,levels of Treg%,VEGF,IL-10 and TGF-βin the recurrence group increased significantly,while levels of IFN-γ,IL-2 and IL-12 decreased significantly (all P<0.05 ). Conclusions Levels of Treg and cytokines can be used to predict the tumor recurrence after liver transplantation for HCC.
5.Evaluation and applications of antibody variable stability
Yu CHEN ; Jing YANG ; Xinying LI ; Tingting ZHOU ; Zhou LIN ; Longlong LUO ; Chunxia QIAO ; Ming Lü ; Yan LI ; Beifen SHEN ; Jiannan FENG
Military Medical Sciences 2014;(5):341-346
Objective To study the intrinsic relationships between the binding energy of the antibody light and heavy chains and the conformational characteristics , physical and chemical properties , and to establish a corresponding mathemat-ical model and evaluate the thermal stability of the antibody molecules , which contribute to the antibody design , optimiza-tion and affinity maturation .Methods Based on bioinformatics and computational biology methods , the antibody′s structur-al information with the crystal diffraction data was analyzed .The conformational character of the variable domain of the antibody was studied using distance geometry and computer graphics technology .With the aid of the intermolecular hydrogen bond formation theory and the reaction free energy theory , the dynamic structure and energy characteristics be-tween the heavy and light chain variable regions of the antibody were studied .Furthermore , using nonlinear fitting and regression analysis, a mathematical model was set up .Results According to simulation and statistic analysis , there was a linear relationship between the binding energy and the number of the intermolecular hydrogen bonding , Van der Waals interaction of the heavy and light chains of the antibody .There was polynomial correlation between the binding energy and the physicochemical properties of the antibody .Using the frequency of amino acid position and the established model , the humanized anti-ricin antibody , which could not obtain the stable engineering cell line , was evaluated and optimized .The stable engineering cell line of the humanized anti-ricin antibody was obtained in the experiment .Conclusion The self structure of the antibody variable region ( conformation and physicochemical properties ) has much effect on its stability . The antibody stability can be improved by structural optimization .
6.Relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders
Chinese Journal of School Health 2023;44(4):582-585
Objective:
To investigate the potential relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders (ASD), to provide a basis for the diagnosis and treatment of children with ASD.
Methods:
A total of 40 ASD children who were treated or recovered in Xi an medical institutions and 16 typically developing (TD) children who were from several kindergatens in Xi an were invited for participation. Sensory characteristics were evaluated by the sensory processing and self regulation checklist, 3D structural brain images were obtained with TIWI, and gray matter volumes were analyzed by voxel based morphometry. Sensory characteristics and gray matter volumes were compared between groups and the relationship between sensory characteristics and different gray matter volumes were analyzed.
Results:
The scores of auditory, visual, tactile, sensory processing ability and sensory under responsivity in the ASD group were lower than those in the TD group ( Z/t =-2.63, -2.57 , -3.11, -2.19, -3.83, P <0.05). Gray matter volumes in nine brain regions increased in the ASD group compared to the TD group, including the left and right posterior inferior lobe, right parahippocamal gyrus, left insula, left media frontal gyrus, left superion occipital gyrus, right superion occipital gyrus, right superion parietal lobe, and right posterion central gyrus ( t =3.53, 3.69 , 3.37, 3.86, 3.61, 3.37, 4.04, 3.38, 3.16, P <0.01). In the ASD group, the scores of visual, vestibular, proprioceptive, sensory processing ability, sensory seeking behavior and sensory over responsivity were negatively correlated with gray matter volumes of left superior occipital gyrus ( r =-0.36, -0.40, -0.39, -0.36, -0.40, -0.36), and the scores of visual, vestibular, and sensory over responsivity were negatively correlated with gray matter volumes of the right superior parietal lobule ( r =-0.36, -0.50, -0.42)( P <0.05).
Conclusion
The presence of paresthesia in children with ASD is associated with gray matter volumes of the left superior occipital gyrus and right superior parietal lobule.
7.Effect of amifostine on proliferation and differentiation of human megakaryocyte Dami cells
Haitao WANG ; Bo YANG ; Xuechun LU ; Bo HU ; Hongqi YANG ; Longlong LUO ; Jie LIN ; Suxia LI ; Hui FAN ; Chunxia QIAO ; Wei WANG ; Xiaoling LANG ; Jing GENG ; Yan LI ; Xiaoxiong WU ; Ming LYU ; Hongli ZHU
Chinese Journal of Pharmacology and Toxicology 2016;30(7):723-727
OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P<0.01),the expression of CD41a was increased by 11.9%,while the expression of CD33 was decreased by 13.6%(P<0.05). Polyploidy cells(16N)were observed,and 4N,8N and 16N cells were increased to 31.56%,8.83% and 3.43%,respectively(P<0.05). CONCLUSION Amf 0.1-1.0 mmol · L-1 can promote the differentiation of Dami cells,but inhibit their proliferation at a high concentration(>1.0 mmol·L-1).
8.Preliminary evaluation of sunitinib as first line therapy in treating patients with metastatic renal cell carcinoma
Jianlin YUAN ; Fuli WANG ; Weijun QIN ; Jun QIN ; Xiaojian YANG ; Chunjuan TIAN ; Rongliang QIN ; Chen SHAO ; Lijun YANG ; Fei LIU ; Geng ZHANG ; Ping MENG ; Longlong ZHANG ; Yu ZHENG ; Guojun WU
Chinese Journal of Urology 2015;(10):742-745
[Abstact] Objective To investigate the efficacy and safety of sunitinib as first line therapy in treating those patients with metastatic renal cell carcinoma ( mRCC ) .Methods A total of 66 patients , including 42 male and 24 female cases ,with metastatic renal cell carcinoma were enrolled from January 2009 to June 2014.The median age was 52 years (range 26-75 years).According to American Joint Committee On Cancer (AJCC) staging,there were 35 cases of T3 stage,31 cases of T4 stage.All patients had distant metastasis ,including single organ metastasis in 52 patients and multiple organ metastasis in 14 cases.Sixty-one patients received prior radical nephrectomy ,5 patients received biopsy .Sixty-two patients were diagnosed as renal clear cell carcinoma and 4 patients were diagnosed as renal papillary cell carcinoma .Sunitinib was administered in standard 4/2 regimens.Briefly, patient takes 50 mg once a day orally for 4 weeks.Then the sunitinib will be stopped for 2 weeks.Six weeks was defined as 1 cycle.It should be continued until disease progression or occurrence of intolerable adverse reactions .The efficacy of sunitinib should be evaluated within 2 cycles.Results The duration of following-up ranged from 5 to 66 months.The efficacy could be evaluated in 63 patients.Two patients ( 3.2%) achieved complete remission .Twelve patients ( 19.0%) achieved partial remission.Forty-five patients (71.4%) demonstrated stable disease and 4 patients (6.3%)
developed progressive disease .The disease control rate was 93.7%(59/63) and the objective response rate was 22.2%(14/63).2 (3.2%) patients died due to the progression of disease .The most commonⅠ-Ⅱadverse events included fatigue in 36 cases ( 57.1%) , thrombocytopenia in 36 cases ( 57.1%) , hand-foot syndrome in 32 cases (50.8%),hypertension in 27 cases (42.9%),neutropenia in 15 cases (23.8%), hypothyroidism in 12 cases (19.0%), diarrhea in 6 cases (9.5%) and alopecia in 4 cases (6.3%).Ⅲ-Ⅳ adverse events were hand-foot syndrome in 4 cases ( 6.3%) , hypertension in 2 cases ( 3.2%) , neutropenia in 5 cases (7.9%) and thrombocytopenia in 5 cases (7.9%).Most mild adverse reactions after symptomatic treatment could be alleviated ,did not affect the medication .When the adverse events returned to the Ⅰ-Ⅱdegree, the 37.5 mg sunitinib was resumed once daily by orally.NoⅢ-Ⅳadverse events were reported again.Conclusions Sunitinib was efficacious in the treatment of advanced renal cell carcinoma.Most mild adverse events were tolerable ,and severe adverse events need medical treatment .
9.Research on the relationship between Foxp3 +Regulatory T cell and tumor recurrence of patients after liver transplantation for hepatocellular carcinoma
Guosheng DU ; Lin ZHOU ; Zhidong ZHU ; Jiyong SONG ; Likui FENG ; Yonggen ZHENG ; Longlong SUO ; Shaozhen YANG
Organ Transplantation 2015;(5):311-315
Objective To discuss the relationship between Foxp3 +regulatory T cell (Treg)and tumor recurrence of patients after liver transplantation for primary hepatocellular carcinoma (HCC) over University of California,San Francisco (UCSF)criteria.Methods Clinical data of 24 patients with HCC undergoing liver transplantation in the Organ Transplantation Research Institute of the 309 th Hospital of People's Liberation Army from January 2010 to December 2013 were retrospectively studied.During the follow-up,4 patients recurred (tumor recurrence group)and other 20 patients did not recur (tumor non-recurrence group).The blood samples of healthy people was selected as control group at the same period.The levels of alpha-fetoprotein (AFP)were compared at different time points of the recurrence group and the non-recurrent group before and after transplantation.The levels of Foxp3 +Treg (Foxp3 +Treg%)were compared at different time points of the tumor recurrence group,the tumor non-recurrence group and the control group before and after transplantation.The relations between expression of Foxp3 +Treg and the levels of AFP,CD3 + and CD8 +T before and after transplantation were analyzed by correlation analysis.Results Compared with the level of Foxp3 +Treg before transplantation and the normal level,the expression of Foxp3 +Treg of patients in tumor non-recurrence group after transplantation firstly decreased,then gradually increased and finally stabilized at a low level.Compared with patients in tumor non-recurrence group,the levels of AFP and Foxp3 +Treg of patients in tumor recurrence group increased obviously and were significantly higher than the normal levels (both in P <0.01).Moreover,abnormal increase of Foxp3 +Treg at early stage was prior to AFP among the patients in tumor recurrence group.Correlation analysis indicated that the change of Foxp3 +Treg was consistent with the changes of AFP,which was positively correlated (P <0.01).But the change of Foxp3 +Treg was contrary to the change of effector T cells (CD3 +T cells and CD8 + T cells),which was negatively correlated (P <0.05-0.01).Conclusions Foxp3 +Treg is closely associated with tumor recurrence after liver transplantation for HCC.In the patients after liver transplantation for HCC over UCSF criteria,the higher Foxp3 +Treg is,the higher the recurrence risk is.Joint detection of AFP is beneficial to find tumor recurrence.
10.Early diagnostic value of miR-191 and miR-494 from fine needle aspiration specimens and peripheral circulation for thyroid carcinoma
Ying YANG ; Feng WEI ; Wei ZHANG ; Longlong WANG ; Lin BAI
Chinese Journal of Endocrinology and Metabolism 2017;33(12):1024-1030
Objective To investigate the different expression levels of death-associated protein kinase ( DAPK) related miR-191 and phosphatase and tensin homolog deleted on chromosome ten ( PTEN) related miR-494 from fine-needle aspiration biopsy ( FNAB) samples and blood of both benign and malignant thyroid nodules, and to find new clinical molecular diagnostic markers. Methods FNAB specimens and peripheral venous blood were collected from 113 patients with thyroid nodules (48 cases of malignant and suspected malignant thyroid nodules, 38 cases of nodular goiter, and 27 cases of thyroid adenomas). The expression levels of miR-191 and miR-494 were detected by realtime fluorescence quantitative reverse transcription PCR ( qRT-PCR ) . qRT-PCR were applied to detect miR-191 and miR-494 expression level in 98 patients with thyroid nodules and peripheral circulation. Receiver operating characteristic curves ( ROC curves) were used to evaluate the sensitivity and specificity of miR-191 and miR-494 to diagnose malignant thyroid nodules. Results (1) The sensitivity of FNAB in diagnosing thyroid cancer was 91. 7% (44/48) and the specificity was 90. 9% (30/33),the diagnostic accuracy was 91. 35%. (2) In FNAB samples, as well as in peripheral circulation, the relative expression of miR-191 in thyroid cancer group is significantly lower than that of the benign group, while the relative expression of miR-494 in thyroid cancer group is significantly higher than that of the benign group (P<0. 05). (3) The sensitivity and specificity of miR-191 and miR-494 were acceptable (area under the ROC curve>0. 7). Sensitivity and specificity of miR-191 in FNAB and peripheral circulation were 76. 9%, 73. 5% and 61. 5%, 64. 1%; miR-494 were 63. 6%,76. 5% and 72. 7%, 84. 6%respectively. (4) In thyroid cancer FNAB samples and peripheral circulation, the differences between the relative expression level of miR-191 and miR-494, and the clinical characteristics of age, gender, nodule size, and calcification, with or without cervical lymph node enlargement, thyroid function and thyroid antibodies with or without abnormalities were not statistically significant(P>0. 05). Conclusion MiR-191 and miR-494 can be used as molecular diagnostic markers for early diagnosis of thyroid carcinoma with adjunctive FNAB.