1.Research and application of TTK and its inhibition in malignant tumors
Xuzhen ZHENG ; Weiquan WANG ; Zhiyu GONG ; De HE
International Journal of Surgery 2024;51(2):138-144
Monopolar spindle 1, also known as threonine and tyrosine kinase (TTK), is a key component of spindle assembly checkpoint (SAC). It is considered to be a monitoring mechanism to ensure mitotic fidelity and genomic stability. TTK is overexpressed in a variety of malignant tumors, and patients with low expression of TTK tend to have a longer survival time, suggesting that it may be used as a biomarker for diagnosis and prognosis. Abnormal expression of TTK often impairs the function of SAC, resulting in irregular mitosis, increased aneuploidy and mitotic disaster, thus promoting the occurrence of tumors. Current studies have shown that TTK inhibitors can inhibit the proliferation of tumor cells and increase the sensitivity of tumor cells to therapy in combination with chemotherapy or radiotherapy to achieve sensitization and attenuated effects. This article will review the research and application of TTK and its inhibitors in malignant tumors.
2.The safety and short-term efficacy of yttrium-90 resin microspheres transarterial radioembo-lization for the treatment of initial unresectable malignant hepatic tumor
Minghua SHAO ; Binbin TAN ; Ying FU ; Zhiyu CHEN ; Yi GONG ; Haisu DAI ; Hailei CHEN ; Hui ZHANG
Chinese Journal of Digestive Surgery 2024;23(7):969-975
Objective:To investigate the safety and short-term efficacy of yttrium-90 [ 90Y] resin microspheres transarterial radioembolization (TARE) for the treatment of initial unresectable malignant hepatic tumor. Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with initial unresectable malignant hepatic tumor who were admitted to The First Affiliated Hospital of Army Medical University from June 2022 to June 2023 were collected. All patients were males, aged (57±4)years. Measurement data with normal distribution were represented as Mean± SD, and comparison before and after treatment within the group was conducted using the paired t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison before and after treatment within the group was conducted using the paired rank sum test. Count data were described as absolute numbers or proportions. Results:(1) Pre-treatment assessment. All 10 patients completed pre-treatment assessment, with 8 cases undergoing once of technetium 99-polymerised protein perfusion test and 2 cases under-going ≥ twice of technetium 99-polymerised protein perfusion test. The ratio of uptake of techne-tium 99-polymerised protein in tumor tissue to normal tissue, the hepatopulmonary shunting ratio and the therapeutic requirement of 90Y resin microspheres in 10 patients were 5.8±1.2, 4.8%±0.8% and (1.10±0.20)GBq, respectively. (2) Treatment strategy of 90Y resin microspheres TARE. Of the 10 patients, cases treated with whole tumor radioembolisation, radioembolisation of the main target lesion+non-target lesion radiofrequency ablation, radioembolisation of the main target lesion+non-target lesion iodine-125 particles implantation, radioembolisation of the liver lobe or liver segment were 6, 2, 1, 1, respectively. During the treatment period, one elderly case did not receive target therapy combined with immunotherapy due to intolerance, and the remaining 9 cases received target therapy combined with immunotherapy. Of the 10 patients, there were 7 cases receiving once of 90Y resin microspheres TARE, and 3 cases receiving twice of 90Y resin microspheres TARE. (3) Follow-up. All 10 patients were followed up for 4.5(range, 3.0-12.0)months. During the follow-up, none of patient had adverse event associated with 90Y resin microspheres TARE. The tumor diameter, alpha-fetoprotein (AFP), abnormal prothrombin, alanine aminotransferase (ALT), aspartate amino-transferase (AST), albumin (Alb), total bilirubin (TBiL), glutamyltransferase (GGT) of the 10 patients were 96(72,135)mm, 26(6,833)μg/L, 290(56,2 997)Au/L, (36±13)IU/L, (41+16)IU/L, (40±4)g/L, (15.3±4.1)μmol/L, (99±68)IU/L before receiving 90Y microspheres TARE. The above indicators of the 10 patients were 63(43,97)mm, 4(3,357)μg/L, 38(25, 142) Au/L, (40±16)IU/L, (51±28)IU/L, (39±4)g/L, (14.4±1.2) μmol/L, (134±93)IU/L after 90 days of receiving 90Y microspheres TARE. There were significant differences in tumor diameter and abnormal prothrombin ( Z=-2.08, -2.24, P<0.05) and there was no significant difference in AFP, ALT, AST, Alb, TBil, GGT ( Z=-1.27, t=0.63, 1.69, 1.73, 0.67, 1.30, P>0.05). During the follow-up period, 5 cases achieved clinical complete response, 4 cases achieved clinical partial remission, and 1 case experienced non-target lesion progression within 30 days after receiving 90Y resin microspheres TARE. The disease remission rate and disease control rate of the 10 patients were 9/10 and 9/10, respectively. None of patient died during follow-up period. Conclusion:90Y resin microspheres TARE for the treatment of initial unresectable malignant hepatic tumor is safe and feasible, and can achieve satisfactory short-term efficacy when combined with other treatment methods.
3.Influencing of preoperative total bilirubin on perioperative complications of hepatolithiasis receiving liver resection
Xia OU ; Yule LUO ; Zhipeng LIU ; Haisu DAI ; Yi GONG ; Ying WU ; Yan JIANG ; Jie BAI ; Shuo JIN ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2024;23(8):1087-1092
Objective:To investigate the influencing of preoperative total bilirubin (TBil) on perioperative complications of hepatolithiasis receiving liver resection.Methods:The retrospective cohort study was conducted. The clinical data of 300 patients with hepatolithiasis who were admitted to 2 medical centers from January 2010 to January 2022 were collected. There were 115 males and 185 females, aged (54±13)years. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers, and the chi-square test was used for comparison between groups. Variables with P<0.10 in the univariate analysis were included into the multivariate analysis. Univariate analysis was conducted using the Logistic regression model,and multivariate analysis was conducted using the Logistic stepwise regression model with backward Wald method. Continuous variables were converted into categorical variables based on commonly reported cutoff values when conducting Logistic regression analysis. Results:(1) Comparison of clinical data of patients with different preoperative TBil. Of 300 patients with hepatolithiasis, there were 252 cases with low level of preoperative TBil as 14.4(11.1,19.7)μmol/L, and there were 48 cases with high level of preoperative TBil as 44.0(31.3,59.8)μmol/L. Of the pati-ents with low level of preoperative TBil, neutrophils percentage was 62%±10%, cases with intra-operative blood transfusion was 29, and cases undergoing anatomical liver resection was 166. Of the patients with high level of preoperative TBil, neutrophils percentage was 70%±11%, cases with intraoperative blood transfusion was 22, and cases undergoing anatomical liver resection was 15. There were significant differences in cases classified as>grade 2 of ASA classification, neutrophils percentage, cases with intraoperative blood transfusion and cases undergoing anatomical liver resection between patients with low and high level of preoperative TBil ( t=5.182, χ2=33.669, 18.775, P<0.05). (2) Comparison of perioperative complications of patients with different preoperative TBil. Of the 252 patients with low level of TBil, there were 151 cases with complications including 35 cases of serious complications, there was 1 case with postoperative liver failure, the duration of postoperative hospital stay was 13.0(10.0,16.0)days. Of the 48 patients with high level of TBil, there were 32 cases with complications including 17 cases of serious complications, there were 6 cases with postoperative liver failure, the duration of postoperative hospital stay was 14.0(10.0,18.8)days. There were significant differences in cases with serious complications and cases with postoperative liver failure between patients with low and high level of preoperative TBil ( χ2=13.041, 20.879, P<0.05). (3) Analysis of factors influencing postoperative serious complications in patients undergoing liver resection. Results of multivariate analysis showed that age, body mass index (BMI), preoperative TBil and volume of intraoperative blood loss were independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis ( odds ratio=3.852, 2.358, 2.935, 5.135, 95% confidence interval as 1.478?9.979, 1.110?5.009, 1.398?6.158, 2.088?12.626, P<0.05). Conclusions:Patients with high level of preoperative TBil have a significantly increased risk of postoperative serious complications and liver failure who receive liver resection for hepatolithiasis. Age, preoperative BMI, TBil and volume of intraoperative blood loss are independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis.
4.Effect of different immune induction therapies on early clinical outcomes of ABO-incompatible kidney transplantation recipients of living relative donor
Yibo HOU ; Sheng CHANG ; Song CHEN ; Bin LIU ; Nianqiao GONG ; Zhiyu ZOU ; Linrui DAI ; Gang CHEN ; Zhishui CHEN ; Weijie ZHANG
Chinese Journal of Organ Transplantation 2023;44(10):620-627
Objective:We employ different regimens of induction therapy in living donor ABO-incompatible kidney transplantation(ABOi-KT) recipients to compare their clinical outcomes during 6 months post-KT.Methods:A retrospective analysis was conducted for the relevant clinical data of 41 ABOi-KT recipients from June 2018 to September 2022.Thirteen recipients on induction therapy of anti-human T lymphocyte porcine immunoglobin(pATG)were enrolled in pATG group; 19 recipients on induction therapy of basiliximab in basiliximab group; 9 recipients on induction therapy of rabbit anti-human thymocyte immunoglobulin(rATG)in rATG group.Differences in age, gender, body mass index(BMI), dialysis modality/duration, sideness of donor kidney, frequency of blood group antibody treatment, dose of rituximab, basic blood group antibody titers of IgG/IgM, and the gender and BMI of recipient's donor were compared for three groups.Immune status was assessed by comparing absolute lymphocyte count before pre-treatment and within 6 months post-KT in recipients under different induction regimens among 3 groups by one-way analysis of variance.Transplant kidney function was assessed by comparing the levels of serum creatinine, estimated glomerular filtration rate(eGFR)and serum urea nitrogen using one-way analysis of variance.The incidence of delayed graft function(DGF), acute rejection(AR)and infection was compared among three groups.Results:Regarding baseline profiles, except for donor age pATG group[(60.23±6.10)years]versus basiliximab group[(51.95±6.97)years]was statistically significant( P=0.002), the differences in the remaining parameters were not statistically significant among three groups(all P>0.05). At Day 1/3/7/10/14 post-KT, absolute lymphocyte counts were(0.17±0.07)×10 9/L, (0.27±0.14)×10 9/L, (0.85±0.40)×10 9/L, (1.05±0.56)×10 9/L and(1.10±0.56)×10 9/L in pATG group and(0.69±0.04)×10 9/L, (0.18±0.21)×10 9/L, (0.57±0.44)×10 9/L, (0.67±0.45)×10 9/L and(0.81±0.46)×10 9/L in rATG group respectively.They were all higher than those in basiliximab group[(0.46±0.18)×10 9/L, (0.67±0.26)×10 9/L, (1.29±0.48)×10 9/L, (1.56±0.49)×10 9/L, (1.75±0.53)×10 9/L]and the differences were statistically significant(all P<0.05). No statistically significant difference existed in absolute lymphocyte count among 3 groups before pre-treatment and after Day 21 post-KT(all P>0.05). At Week 1/2/4/12/24 post-KT, the differences in serum levels of creatinine and urea nitrogen were not statistically significant( P>0.05). At Month 1/3 post-KT, eGFR was(47.24±14.51)and(49.94±14.31)ml·min -1·(1.73 2) -1 in rATG group and they were lower than(67.36±21.60)and(65.00±14.67)ml·min -1·(1.73 2) -1 in basiliximab group with a statistically significant difference( P<0.05). However, at Week 1/2/24 post-KT, no statistically significant difference existed in eGFR among 3 groups( P>0.05). In ATG, basiliximab and rATG groups, DGF(1 case, 1 case, 1 case), AR(2 cases, 2 cases, 1 case)and infection(4 cases, 7 cases, 3 cases)occurred during 6 months post-KT. Conclusions:Through a limited sample of single centers, no statistically significant difference existed in graft function recovery for ABOi-KT recipients on induction therapies of pATG, basiliximab and rATG.And DGF, AR and infections occurred in all three groups.However, there were little inter-group differences.
5.Short-term and long-term prognosis analysis of anatomical liver resection for the treatment of perihilar cholangiocarcinoma
Xianghao YE ; Zhipeng LIU ; Haisu DAI ; Yi GONG ; Hao LI ; Zhihua LONG ; Wei WANG ; Yuhan XIA ; Shujie PANG ; Longfei CHEN ; Xingchao LIU ; Haining FAN ; Jie BAI ; Yan JIANG ; Zhiyu CHEN
Tumor 2023;43(6):506-515
Objective:To explore the short-term and long-term prognostic outcomes of anatomical liver resection(AR)for patients with perihilar cholangio-carcinoma. Methods:This is a retrospective study.All data were obtained from 4 centers,including The First Affiliated Hospital of Army Medical University,Eastern Hepatobiliary Hospital of Naval Medical University,Sichuan Provincial People's Hospital and Affiliated Hospital of Qinghai University,of a multi-center database.A total of 305 consecutive perihilar cholangiocarcinoma patients receiving radical resection between January 2013 and June 2021 were included in this study.According to the method of liver resection,all patients were divided into the AR group(n=205)and the non-anatomical liver resection(NAR)group(n=100).The baseline characteristics,short-term prognosis and long-term prognosis of the 2 groups were compared. Results:The perioperative transfusion rate and the 30-day complication rate were significantly lower in the AR group than those in the NAR group(P<0.05).There was no statistically significant difference in the survival rates between the AR and the NAR groups(P>0.05). Conclusion:The 2 hepatic resection modalities had no obvious effect on the long-term prognosis of perihilar cholangiocarcinoma patients after radical resection,but choosing AR tends to achieve a better short-term prognosis and is worth promoting in clinical practice.
6.Clinical efficacy of transarterial chemoembolization combined with immunotherapy plus target therapy for advanced unresectable intrahepatic cholangiocarcinoma
Hui ZHANG ; Zhiyu CHEN ; Yi GONG ; Haisu DAI ; Binbin TAN ; Wei MU ; Leida ZHANG
Chinese Journal of Digestive Surgery 2021;20(S2):37-40
Advanced intrahepatic cholangiocarcinoma(ICC) is one of the most common hepatic malignant tumors besides hepatocellular carcinoma, with occult onset, limited treatment and poor prognosis. Systemic treatment is a recommendable solution for advanced unresectable ICC. The authors reported the clinical experience of an ICC patient who underwent transarterial chemoembolization combined with immunotherapy plus target therapy.
7.Primary application of progressive teaching on endoscopic ultrasonography training program
Xiaoyin ZHANG ; Min ZHAO ; Zhiyu ZENG ; Fang WANG ; Wei GONG ; Zhendong JIN
Chinese Journal of Digestive Endoscopy 2018;35(8):580-582
Objective To compare the effect of progressive teaching pattern with traditional long-term training on improvement of trainees ability of endoscopic ultrasonography ( EUS ) . Methods Ten learners who have achieved competence on routine endoscopic procedures but without any knowledge and skills on EUS procedures were enrolled in the study, and were randomly divided into two groups according to the sequence number. Learners with odd number received traditional long-term training, and the even number learners received progressive teaching. The proficiency of EUS knowledge and skills in the two groups were compared after one-year learning. Results At the final examination, the learners′ ability of mastering EUS was higher, and the study leave time was shorter in the progressive teaching group than that in the traditional long-term training group. however, we didn′t have a statistical comparison owing to the few numbers of trainees. Conclusion Progressive teaching pattern is superior to the traditional training, and it should be advocated when hospitals are relatively understaffed.
8.Expressions of activation antigens CD69 and HLA-DR in peripheral blood mononuclear cells and skin lesions of patients with psoriasis vulgaris
Wenjuan CHEN ; Junying GU ; Yu GONG ; Zhiyu LIU ; Hui XU ; Huizi XIONG ; Yuling SHI
Chinese Journal of Dermatology 2015;(9):625-628
Objective To investigate changes in expressions of activation antigens CD69 and HLA-DR in CD3+T lymphocytes in peripheral blood and skin lesions in patients with psoriasis vulgaris. Methods Peripheral blood samples were obtained from 20 patients with psoriasis vulgaris and 20 healthy controls, and skin specimens from the lesions of 15 out of the 20 patients and 10 healthy controls. Flow cytometry was performed to quantify the expressions of CD69 and HLA-DR in peripheral blood CD3+T cells, and an immunohistochemical study to measure the expression of HLA-DR in skin specimens. Statistical analysis was carried out by a two-sample t-test and Pearson correlation analysis with the SPSS 19.0 software. Results Compared with the healthy controls, the patients with psoriasis vulgaris showed increased expression rates of CD69 (4.70%± 1.90%vs. 1.56%± 0.95%, t=6.629, P<0.01)and HLA-DR (8.97%± 1.79% vs. 3.02% ± 1.15%, t= 6.204, P< 0.01)in peripheral blood. Pearson correlation analysis revealed that the percentage of CD3+HLA-DR+cells in peripheral blood was positively correlated with the psoriasis area and severity index (PASI)score (r=0.5626, P<0.05). The expression rate of HLA-DR was significantly higher in the dermis (64.87%± 17.31%vs. 19.80%± 5.69%, t=7.916, P<0.01), but lower in the epidermis(11.80%± 5.55%vs. 27.40%± 8.61%, t=5.479, P<0.01)in the psoriatic specimens compared with the control specimens. Immunohistochemically, HLA-DR was widely expressed in the dermis of psoriatic lesions, but mainly distributed around blood vessels in the control skin. Conclusions There is an aberrant activation of CD3+T cells in peripheral blood and inflammatory cells in skin lesions in patients with psoriasis vulgaris, and the percentage of CD3 +HLA-DR+ cells in peripheral blood is correlated with the severity of psoriasis vulagaris.
9.Effect of siRNA interfering vascular endothelial growth factor on radiation sensitization of malignant melanoma
Dequan PANG ; Yingman WANG ; Yunfei DAI ; Jing BAI ; Weiguo ZHENG ; Fengling GONG ; Zhiyu ZHAO
Chinese Journal of Biochemical Pharmaceutics 2015;(8):48-51
Objective To investigate the role of a small RNA interference against VEGF in radiation sensitivity in melanoma .Methods A375 human melanoma cell lines were transplanted into nude mice ,which with malignant melanoma were randomly divided into control group , VEGF negative plasmid group and VEGF positive plasmid group, followed by 4Gy irradiation twice a week for 2 weeks.The volume of tumor was calculated twice a week, the area of tumor necrosis was assayed by HE,the expression of VEGF in tumor was determined by Western-blot and Immunohistochemical. ResuIts The expression of VEGF in VEGF positive plasmid group decreased significantly (P<0.05), VEGF positive group had more tissue necrosis, tumor growth was significantly inhibited (P<0.05).ConcIusion siRNA-VEGF in tumor injection liposome encapsulated in malignant melanoma has a role in the radiation sensitization, which provides an experimental basis for the clinical development of targeted therapy combined with radiotherapy for the treatment of VEGF gene.
10.Quality and quantity classification models of Fructus Amomi applying electronic nose with multiple mathematical statistics methods
Huiqin ZOU ; Jianting GONG ; Liying ZHAO ; Ou TAO ; Jiahui LI ; Zhiyu REN ; Yonghong YAN
Journal of International Pharmaceutical Research 2015;(4):513-518
Objective Fructus Amomi(Sharen) is derived from the dry ripe fruit of Amomum villosum Lour., A.villosum Lour. var. xanthioides T.L. Wu et Senjen and A.longiligulate T.L.Wu, which is widely utilized for its clinic effects on digestive system. However, Fructus Amomi from different species and habitats, possessing different quality, is difficult to identify. In this study, we aim to develop a simple, rapid and reliable method for authentication of Fructus Amomi. Methods Twenty-five batches of samples of Fructus Amomi were collected and electronic nose was introduced into analyzing their odor with multiple mathematical statistics methods. Na?ve bayes network (NBN), radical basis function (RBF) and random forest (RF) were applied to establish different classifiers while BestFirst+CfsSubsetEval (BC) was used to screen the attributes for searching sensor array with higher contributions. Results Firstly, after attribute-screening via BC, the established discriminative models via NBN, RBF and RF could successfully identify genuine and non-genuine samples, presenting correct judging ratios of 78% and 84% through ten-fold cross validation and external test set validation, respectively. Besides, quantity predictive models were constructed as well. In case of content of bornyl acetate, one of the effective components in Fructus Amomi, values were higher than 3.5 mg/g and lower than 1.8 mg/g with sensor response of 0.04 and 0.03, respectively. Conclusion In this paper, quality discriminative model and quantity predictive model of Fructus Amomi were established via electronic nose and multiple mathematical statistics methods. It indicates that electronic nose could be a promising method for quality evaluation of Chinese material medica.

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