1.Feasibility of gastric cancer organoid models for personalized drug screening
Hongkai FAN ; Yingying GUAN ; Lumin WANG ; Fanwei ZENG ; Yirui YIN
Chinese Journal of Tissue Engineering Research 2025;29(25):5345-5350
BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.
2.Combining T1 mapping and diffusion weighted imaging for predicting tumor-infiltrating lymphocyte level in invasive breast cancer
Fan MENG ; Junhui YUAN ; Shaobo FANG ; Xiaoxian ZHANG ; Lanwei GUO ; Tiandong CHEN ; Hongkai ZHANG ; Jingrong QU ; Renzhi ZHANG ; Xuejun CHEN
Chinese Journal of Medical Imaging Technology 2025;41(1):84-89
Objective To observe the value of T1 mapping combining diffusion weighted imaging(DWI)for noninvasive preoperative predicting tumor-infiltrating lymphocyte(TIL)level in invasive breast cancer.Methods Totally 143 patients with invasive breast cancer were retrospectively collected and divided into high group(TIL≥10%,n=73)and low group(TIL<10%,n=70)according to TIL level by postoperation pathology.Clinicopathological information were collected,MRI features of breast cancer lesions were documented,mean T1 values(T1mean)and mean ADC values(ADCmean)were measured,and then were compared between groups.Multivariate logistic regression analysis was used to identify independent predictive factors of TIL levels,and a nomogram was constructed based on regression model.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the predictive value for TIL levels.Results Compared with low group,high group had higher proportion of human epidermal growth factor receptor 2(HER2)positivity(P<0.05),and showed more circular/oval shapes and more smooth margins but less peritumoral edema(all P<0.05).Significant differences of lesions enhancement pattern was found between groups(P<0.05).T1mean and ADCmean were both higher in high group than those in low group(both P<0.05).Lesions enhancement pattern,T1mean and ADCmean were all independent predictors of TIL levels in breast cancer.The AUC of nomogram combining the above 3 factors for predicting TIL level was 0.848,significantly higher than that of lesions enhancement pattern(AUC=0.569,Z=5.384,P<0.05)and T1mean(AUC=0.662,Z=3.876,P<0.05),but not statistically different with that of ADCmean(AUC=0.814,Z=1.578,P=0.115).Decision curve analysis showed that this nomogram had good clinical application value.Conclusion Combining T1 mapping and DWI could effectively predict level of TIL level in breast cancer before surgery.
3.Feasibility of gastric cancer organoid models for personalized drug screening
Hongkai FAN ; Yingying GUAN ; Lumin WANG ; Fanwei ZENG ; Yirui YIN
Chinese Journal of Tissue Engineering Research 2025;29(25):5345-5350
BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.
4.Combining T1 mapping and diffusion weighted imaging for predicting tumor-infiltrating lymphocyte level in invasive breast cancer
Fan MENG ; Junhui YUAN ; Shaobo FANG ; Xiaoxian ZHANG ; Lanwei GUO ; Tiandong CHEN ; Hongkai ZHANG ; Jingrong QU ; Renzhi ZHANG ; Xuejun CHEN
Chinese Journal of Medical Imaging Technology 2025;41(1):84-89
Objective To observe the value of T1 mapping combining diffusion weighted imaging(DWI)for noninvasive preoperative predicting tumor-infiltrating lymphocyte(TIL)level in invasive breast cancer.Methods Totally 143 patients with invasive breast cancer were retrospectively collected and divided into high group(TIL≥10%,n=73)and low group(TIL<10%,n=70)according to TIL level by postoperation pathology.Clinicopathological information were collected,MRI features of breast cancer lesions were documented,mean T1 values(T1mean)and mean ADC values(ADCmean)were measured,and then were compared between groups.Multivariate logistic regression analysis was used to identify independent predictive factors of TIL levels,and a nomogram was constructed based on regression model.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the predictive value for TIL levels.Results Compared with low group,high group had higher proportion of human epidermal growth factor receptor 2(HER2)positivity(P<0.05),and showed more circular/oval shapes and more smooth margins but less peritumoral edema(all P<0.05).Significant differences of lesions enhancement pattern was found between groups(P<0.05).T1mean and ADCmean were both higher in high group than those in low group(both P<0.05).Lesions enhancement pattern,T1mean and ADCmean were all independent predictors of TIL levels in breast cancer.The AUC of nomogram combining the above 3 factors for predicting TIL level was 0.848,significantly higher than that of lesions enhancement pattern(AUC=0.569,Z=5.384,P<0.05)and T1mean(AUC=0.662,Z=3.876,P<0.05),but not statistically different with that of ADCmean(AUC=0.814,Z=1.578,P=0.115).Decision curve analysis showed that this nomogram had good clinical application value.Conclusion Combining T1 mapping and DWI could effectively predict level of TIL level in breast cancer before surgery.
5.Early myocardial strain characteristics in type 2 diabetic mellitus mice evaluated by 7.0 T cardiac MR
Chunyan SHI ; Hongkai ZHANG ; Yifeng GAO ; Nan ZHANG ; Dongting LIU ; Lin YANG ; Lei XU ; Zhanming FAN
Chinese Journal of Radiology 2022;56(5):569-575
Objective:To investigate the characteristics of early myocardial mechanics changes in diabetic cardiomyopathy (DCM).Method:Sixty healthy 4-week-old male C57BL/6J mice were randomly divided into the T2DM group ( n=30) and the control group ( n=30). The T2DM group was fed with high-fat diet for 4 weeks, and accepted injection of a single high-dose of streptozotocin (STZ) intraperitoneally. Finally, the model was established successfully in 23 mice. The control group was fed with a normal diet and treated with citrate buffer liquid at an equal dose as T2DM group. Then, nine mice were randomly selected from each of the two groups every 4 weeks until the end of the 24th week. Six of the nine mice were randomly selected to perform 7.0 T MR scanning after measuring blood glucose and body weight. Cine images were acquired through cardiovascular MR feature tracking (CMR-FT). The obtained parameters included the left ventricle global peak circumferential strain (LV-GPCS), left ventricle global peak radial strain(GPRS) and the ejection fraction (EF), etc. The rest three mice were sacrificed for observation of the changes of interstitial fibers and micro-vessels in myocardial tissue with Sirius red staining. One-way analysis of variance (ANOVA) and t test were used for comparison. Results:There were significant differences in blood glucose levels between the two groups during the observation period ( P<0.05). In the 4 th-24 th week, the value of GPCS in T2DM group showed a downward trend, and the difference was statistically significant ( F = 8.23, P<0.001). Compared with the control group, the value of GPCS in T2DM group was statistically significant at the 20 th and 24 th week (the 20 th week: -11.4%±2.1% in the T2DM group vs. -14.3%±1.9% in the control group, t=2.54, P=0.029;the 24 th week: -12.3%±1.7% in the T2DM group vs. -14.6%±1.8% in the control group, t=2.35 , P=0.040), while the EF value was different at the 24 th week (51%±5% in the T2DM group vs. 62%±6% in the control group, t=3.38, P=0.007). There was no significant difference in the GPRS of the T2DM mice group over time or compared with the controls ( P>0.05). Moreover, the pathological results showed that the myocardial interstitial fibers in the T2DM group had remarkably increased since the 12 th week. Conclusions:The alterations in myocardial interstitial fibers and myocardial contractility appeared early in T2DM mice. Especially, the left ventricle global peak circumferential strain value is superior to the EF value in reflecting the early changes in DCM.
6.Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine.
Xingdong ZHOU ; Hui WANG ; Qun JI ; Mingjuan DU ; Yuexia LIANG ; Huanhuan LI ; Fan LI ; Hang SHANG ; Xiujuan ZHU ; Wei WANG ; Lichun JIANG ; Alexey V STEPANOV ; Tianyu MA ; Nanxin GONG ; Xiaodong JIA ; Alexander G GABIBOV ; Zhiyong LOU ; Yinying LU ; Yu GUO ; Hongkai ZHANG ; Xiaoming YANG
Protein & Cell 2021;12(10):818-823
7.Influence of intravenous immunoglobulin on blood compatibility testing
Hongkai LU ; Xirong HE ; Wenjing WANG ; Lida CHEN ; Fan ZHANG ; Weijie GUO ; Xixi LIU ; Yongtong CAO
Chinese Journal of Blood Transfusion 2021;34(6):610-612
【Objective】 To study the effect of intravenous immunoglobulin(IVIG) on the detection of blood transfusion compatibility in patients. 【Methods】 56 patients, submitted to our Hospital from March 1, 2017 to December 31, 2020, were enrolled as the research objects. They had negative unexpected antibody screening, major crossmatch incompatibility with the same blood type donors, and had a history of IVIG infusion. ABO and RhD blood groups typing, unexpected antibodies screening, crossmatch, direct antiglobulin test, indirect antiglobulin test, and acid elution test were all conducted by microcolumn gel method. 【Results】 After IVIG infusion, the initially major crossmatch incompatibility with the same blood type donors turned into compatiblity with O-type donors. Among them, 2 patients had transient discrepancy in ABO forward and reverse blood typing due to the IVIG infusion. IgG anti-A were detected in the red blood cell elution of 37 A-type patients; IgG anti-B in 2 B-type patients; 3 cases of IgG anti-A+ anti-B and 14 cases of solo IgG anti-A in 17 AB-type patients. 3 batches of IVIG preparations were detected randomly, IgG anti-A titer was 32-64, and IgG anti-B titer was 8-16. 【Conclusion】 The discrepancy in ABO forward and reverse blood typing and major crossmatch incompatibility with the same blood type donors may occur after non-O type patients received IVIG, which contains IgG types of anti-A and anti-B. In this situation, it is recommended to prepare major crossmatched O-type washed red blood cells to ensure the safety and effectiveness of clinical blood transfusion.
8.Influencing factors of perioperative red blood cell transfusion in patients underwent lung transplantation
Wenjing WANG ; Qi WANG ; Ru ZHAO ; Lida CHEN ; Lulu WANG ; Weijie GUO ; Xixi LIU ; Fan ZHANG ; Xirong HE ; Hongkai LU
Chinese Journal of Blood Transfusion 2021;34(2):135-139
【Objective】 To explore the influencing factors of perioperative red blood cell transfusion in patients underwent lung transplantation, so as to provide reference for perioperative blood management (PBM) of lung transplantation patients. 【Methods】 The clinical data of 173 lung transplant patients completed in China-Japan Friendship Hospital from March 2017 to June 2019 were retrospectively analyzed. The patients were divided into two groups according to perioperative red blood cell transfusion volume: large blood transfusion group (transfusion red blood cell volume ≥6 U, n=66) and non-large blood transfusion group (red blood cell transfusion volume <6 U, n=107). The basic information, preoperative laboratory test results, and surgical status of the two groups were statistically analyzed.The clinical data of the two groups were analyzed by univariate analysis. The factors of P<0.15 were included in the binary logistic regression analysis, and the independent influencing factors of perioperative massive blood transfusion in patients with lung transplantation were found. 【Results】 Univariate analysis of clinical data of the two groups of patients (large blood transfusion group vs. non-large blood transfusion group) showed that the differences of smoking history ratio [44(66.7%) vs 87(81.3%)], BMI(20.8±4.5 vs 22.5±4.0)(P<0.05), preoperative Hb [124(111, 138.8) vs 138(126, 149)], preoperative Hct [37.9(34.8, 42.5) vs 41.3(37.9, 44.6)], surgery duration(327.9±107.7 vs 238.4±77.0), intraoperative blood loss(1 108.6±1342.0 vs 341.8±270.8) and single lung transplantation [28(42.4%) vs 84(78.5%)] (P<0.01) were statistically significant. Logistic regression analysis showed that intraoperative blood loss (OR=1.001, P<0.05), surgery duration (OR=1.006, P<0.05), preoperative Hb (OR=0.973, P<0.01), lung transplantation type(single or double lung transplantation)( OR=0.247, P<0.05) and extracorporeal membrane oxygenation (ECMO) (OR=0.187, P<0.01) were independent factors influencing red blood cell transfusion during lung transplantation. 【Conclusion】 Intraoperative blood loss and surgery duration are risk factors for massive blood transfusion during the perioperative period. And the use of ECMO, preoperative Hb, single lung transplantation (compared to double lung transplantation) are protective factors for perioperative massive blood transfusion.

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