1.Effects of donor-Ag specific T cell vaccination on inhibiting Flt3-L-induced acute liver allograft rejection
Zhenlin ZHAO ; Chenye ZHAO ; Yanbing XIE ; Bo YANG ; Jirong SU
Chinese Journal of Immunology 2016;32(3):327-331
Objective:To investigate the effect and mechanism of donor-Ag specific T cell vaccination on inducing specific immune tolerance of allogenic liver transplantation and the mechanism of immune privilege of liver transplantation .Methods:CBA mice were recipients,B6 mice were donors,T cell vaccination (TCV) were made from the attenuated spleen cells of CBA mice ,which were stimulated by Con A and were challenged with the spleen cells of B 6 mice.There are 3 groups in this experiment:Transplant control group:Orthotopic liver transplantation ( OLT) were performed with the recipients of CBA mice and donors of B 6 mice;Flt3-L treating group:OLT were performed with the recipients of CBA mice and donors of B 6 mice treated with Flt3-L;TCV group:OLT were performed with the recipients of CBA mice inoculated with TCV and donors of B 6 mice treated with Flt3-L.Median survival time (MST) of liver grafts was recorded, IL-4, IL-10 and IFN-γin peripheral blood were tested after transplantation in each group .One-way mixed lymphocyte reaction ( MLR) were carried out with effectors of spleen cells from CBA mice and stimulator of spleen cells from B 6 mice at the 5th day after transplantation.The apoptosis of liver graft infiltrating cells (GICs) were analyzed by flow cytometric analysis at the 5th day after transplantation.Results: Flt3-L treating donor activated allogenic acute rejecting reaction , TCV vaccinating recipient before and after transplantation significantly depressed the acute immune rejecting reaction mediated by Flt 3-L.The liver grafts were accepted by recipient without the presence of Flt 3-L.The cytokines test show that the serum value of IL-4 and IL-10 were increased in Transplant control group and TCV group ,but decreased in Flt3-L treating group.The value of IFN-γwas increased in Flt3-L treating.
2.Risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer and application value of its nomogram prediction model
Chen CHENG ; Yunhua WU ; Zhengshui XU ; Chenye ZHAO ; Xiaopeng LI ; Junhui YU ; Jing GUO ; Jianbao ZHENG ; Guangbing WEI ; Xuejun SUN
Chinese Journal of Digestive Surgery 2021;20(3):331-338
Objective:To investigate the risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer, and application value of a nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 228 patients with stage Ⅱ-Ⅲ colon cancer who underwent radical resection in the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to June 2016 were collected. There were 118 males and 110 females, aged from 25 to 87 years, with a median age of 62 years. All patients underwent open or laparoscopic-assisted radical resection of colon cancer. Observation indicators: (1) postoperative tumor recurrence; (2) risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer; (3) development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. Follow-up using outpatient examination and telephone interview was performed to detect postoperative 3-year tumor recurrence up to June 2019. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the Pearson chi-square test or Fisher exact probability. Multivariate analysis was performed using Logistic stepwise regression analysis. The independent risk factors were included into R 3.6.1 software to construct a nomogram prediction model. The receiver operating characteristic curve (ROC) was drawed, and the area under curve (AUC) was used to evaluate discrimination of the nomogram prediction model. The calibration chart with R software was used to evaluate consistency of the nomogram prediction model. Results:(1)Postoperative tumor recurrence: 53 of 228 patients had postoperative tumor recurrence including 19 cases with locoregional recurrence and 34 cases with distant metastasis. Of the 34 patients with distant metastasis, there were 14 cases with liver metastasis, 7 cases with lung metastasis, 4 cases with brain metastasis, and 9 cases with multiple metastasis or isolated metastasis in other sites. The time to recurrence was 12 months (range, 6-19 months). (2) Risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer:results of univariate analysis showed that bowel obstruction, preoperative carcinoembryonic antigen (CEA) level, ascites, vascular invasion were related factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( χ2=4.463, 13.622, 10.914, 5.911, P<0.05). Pathological N stage was also a related factor for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( P<0.05). Results of multivariate analysis showed that preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 were independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( odds ratio=3.129, 3.071, 7.634, 3.439, 15.467, 95% confidence interval as 1.328-7.373, 1.047-9.007, 1.103-52.824, 1.422-8.319, 3.498-68.397, P<0.05). (3) Development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer: based on preoperative CEA level, ascites, vascular invasion and pathological N stage of multivariate analysis, a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was developed using R 3.6.1 software. The nomogram score was 41.7 for preoperative CEA level >5 μg/L, 41.0 for ascites, 74.2 for vascular invasion, 45.1 and 100.0 for pathological N stage as stage N1 and N2, respectively. The total of different scores for risk factors corresponded to the probability of postoperative recurrence. The ROC of nomogram for recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was drawed,with the AUC of 0.805(95% confidence interval as 0.737-0.873, P<0.05). The calibration chart showed a good consistency between the probability of recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer predicted by nomogram and the actual probability of postoperative recurrence. Conclusions:Preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 are independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. The nomogram prediction model contributes to prediction of the recurrent risks after radical resection of stage Ⅱ-Ⅲ colon cancer.
3.Stability of iodine content in potassium iodate iodized salt in Jilin Province
Xin SHI ; Xiaoqiu ZHAO ; Hongyuan HUANG ; Qiyue TAN ; Ke SUN ; Jinze LI ; Chenye LI ; Zhenwei GAN ; Shuhua ZHAO
Chinese Journal of Endemiology 2022;41(4):290-293
Objective:To study the stability and influencing factors of potassium iodate iodized salt that can be sold in Jilin Province.Methods:In November 2020, 10 large supermarkets were randomly selected in Jilin Province, and two kinds of potassium iodate iodized salts were randomly selected in each supermarket, with five copies of each kind, a total of 100 samples of iodized salt, and the iodine content was determined by spectrophotometry (iodide-starch blue light method). Iodized salt samples were classified according to different salt species (mine salt, sea salt and lake salt) and different production processes (refined salt and non-refined salt). The salt was stored at room temperature, and the iodine content in the salt was measured at 0, 10 and 20 days after opening the packaging. The iodine content attenuation rates of different salt species and different production processes were compared.Results:The mine salt, sea salt and lake salt in iodized salt samples were 45, 45 and 10 portions, respectively. The iodine contents of the 0th day of storage [(19.89 ± 1.38), (20.62 ± 1.91), (19.78 ± 1.01) mg/kg] were compared, and the difference was not statistically significant ( F = 2.57, P = 0.093). On the 10th day, the iodine content of mine salt was lower than that of sea salt and lake salt, and the differences were statistically significant ( P < 0.05); on the 20th day, the iodine content of mine salt was lower than that of sea salt, and the difference was statistically significant ( P < 0.05). There was a significant difference in the iodine content of mine salt stored at 0, 10 and 20 days ( F = 90.62, P < 0.001). The iodine content of sea salt and lake salt on the 20th day was significantly lower than that on the 0th and 10th day, and the differences were statistically significant ( P < 0.05). The iodine content attenuation rates of mine salt, sea salt and lake salt on the 0 - 10 days was compared with that on the 10 - 20 days, and the differences were statistically significant ( Z = 2.24, 2.94, 2.80, P < 0.05). There was a significant difference in the iodine content attenuation rates of mine salt, sea salt and lake salt during the 0 - 10 days of storage ( Z = 24.05, P < 0.001), there was no statistically significant difference in the iodine content attenuation rates on 10 - 20 days ( Z = 5.86, P = 0.053). There was no significant difference in iodine content attenuation rates between refined salt and non-refined salt on 0 - 10, 10 - 20 days ( Z = 1.16, 0.28, P > 0.05). There was no statistical significant difference in the iodine content attenuation rates of refined salt and non-refined salt on the 0 - 10 days compared with those of 10 - 20 days ( Z = 0.76, 1.90, P > 0.05). Conclusions:Iodine loss occurs at 20 days after opening the packaging of iodized salt in Jilin Province. The attenuation of iodine content is less affected by salt species and production processes. It is recommended to eat iodized salt within 20 days after opening the packaging.
4.Ample dietary fat reduced the risk of primary vesical calculi by inducing macrophages to engulf budding crystals in mice.
Huiling CHEN ; Kaiqiang HU ; Yaru LIANG ; Yuqi GAO ; Chenye ZENG ; Kang XU ; Xiaojin SHI ; Liyuan LI ; Yuemiao YIN ; Yi QIAO ; Ying QIU ; Qingfei LIU ; Zhao WANG
Acta Pharmaceutica Sinica B 2022;12(2):747-758
Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d,l-choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d,l-choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14 (Cxcl14) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.
5.Comparison of short-term efficacy between laparoscopic surgery with natural orifice specimen extraction and laparoscopic-assisted surgery for radical resection of rectal cancer
Xiaopeng LI ; Jing LI ; Wei WANG ; Mingchao MU ; Chenye ZHAO ; Zilu CHEN ; Junhui YU ; Xiongwei HUO ; Xuejun SUN
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):990-995
【Objective】 To explore the feasibility, safety and clinical application value of laparoscopic radical rectal cancer surgery with natural orifice specimen extraction (NOSE) by comparing the postoperative pathological data, surgery-related variables and postoperative recovery between laparoscopic radical rectal cancer surgery with NOSE and laparoscopic-assisted radical rectal cancer surgery. 【Methods】 A retrospective analysis was conducted on 74 patients who underwent radical rectal cancer surgery with anus preservation in the Department of General Surgery of The First Affiliated Hospital of Xi’an Jiaotong University from July 2017 to April 2022. Among them, 38 cases underwent surgery with specimen extraction through an abdominal auxiliary incision (auxiliary incision group), and 36 cases underwent surgery with specimen extraction through a natural orifice (NOSES group). The differences in the efficacy of the two surgeries were evaluated by comparing the postoperative pathological data, surgical variables, and postoperative recovery of the two groups. 【Results】 There were no statistically significant differences in general data and postoperative pathological data between the two groups (all P>0.05). The NOSES group exhibited significantly shorter operative time, time to first flatus, time to first oral intake postoperatively, and postoperative hospital stay compared to the auxiliary incision group (all P<0.05). However, there were no statistically significant differences in intraoperative blood loss, postoperative complications, and whether secondary surgeries were performed (all P>0.05). 【Conclusion】 Laparoscopic surgery with NOSE for rectal cancer is safe and feasible with minimally invasive and accelerated recovery, which is worth promoting and applying in clinical practice.
6.Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling.
Kezheng PENG ; Chenye ZENG ; Yuqi GAO ; Binliang LIU ; Liyuan LI ; Kang XU ; Yuemiao YIN ; Ying QIU ; Mingkui ZHANG ; Fei MA ; Zhao WANG
Acta Pharmaceutica Sinica B 2023;13(6):2680-2700
Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.