1.Mechanisms of Neiyiting Decoction in Preventing Postoperative Recurrence of Endometriosis by Inhibiting Macrophage M1 Polarization Through the TREM1/TLR4/NF-κB Signaling Pathway
Lijuan LU ; Weiwei ZENG ; Jingwen WANG ; Lurong ZHANG ; Ying LIU ; Xueliang SUN ; Wen XU ; Xiaohui FANG ; Yichao YAN ; Qinhua XIA
Journal of Sichuan University (Medical Sciences) 2025;56(2):371-381
Objective The high post-surgery recurrence rate of endometriosis(EMs)has emerged as a challenge in the long-term manaagement of the condition.This study is aimed at investigating the mechanisms of Neiyiting(NYT)decoction in preventing postoperative recurrence of EMs.Methods An animal model of EMs postoperative recurrence and a model of endometrial stromal cells(hEM15A)cocultured with macrophages(RAW 264.7 cell line)were established for both in vivo and in vitro experiments.An autotransplantation method was used to establish a rat model of EMs.The rats were divided into 4 groups(6 rats per group)and received the corresponding treatments:a Model group receiving distilled water,a Gestrinone group receiving gestrinone at 0.325 mg/kg,a low-dose NYT(NYT-L)group receiving NYT decoction at 5.04 g/(kg-d),and a high-dose NYT(NYT-H)group receiving NYT decoction at 10.08 g/(kg-d).The treatment was administered for 3 weeks via intragastric gavage.In addition,6 SD rats were randomly selected for the control group(Control group),and were given distilled water for 3 weeks via intragastric gavage.The sizes and pathological changes of recurrent lesions in EMs rats were observed.Immunohistochemistry and qRT-PCR were performed to assess the expression of M1 macrophage marker CD86 protein and mRNA in vivo.Additionally,immunohistochemistry and qRT-PCR were used to assess the expression of indicator proteins related to the triggering receptor expressed on myeloid cells 1(TREM1)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway and mRNA.The proliferation of hEM15A cells in the coculture experiment was observed.Flow cytometry was performed to determine the polarization of RAW264.7 macrophages,and qRT-PCR was used to determine the expression levels of inducible nitric oxide synthase(iNOS)and interleukin 1β(IL-1β)mRNA.Western blot was performed to determine the expression of signaling pathway-related indicator proteins in vitro.ELISA was performed to determine the levels of inflammatory factors in vitro.Results Compared with the Model group,the volume of recurrent lesions in the NYT-H group was reduced(P<0.01).Findings from the macrophage M1 polarization assessment showed that the expression levels of CD86 protein and mRNA in the recurrent lesions of the Model group were higher than those in the control group(P<0.01).The expression levels of CD86 protein and mRNA in the recurrent lesions of the NYT-H group were lower than those of the Model group(P<0.01).In addition,the RAW 264.7 cell experiment further verified that NYT decoction could reduce the number of CD86-positive macrophages induced by plasmids overexpressing TREM1 and reduce the expression of IL-1β and iNOS mRNA(P<0.01).The results of the hEM15A cell proliferation assay showed that NYT decoction down-regulated KI-67 protein expression in hEM15A cells induced by macrophage M1 polarization(P<0.01).The results of TREM1/TLR4/NF-κB signaling pathway showed that the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the Model group were higher than those of the control group(P<0.01).Compared with those in the Model group,the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the NYT-H group were lower(P<0.01).In addition,the coculture experiment of RAW264.7 and hEM15A cells further confirmed that NYT decoction reduced the expression of TREM1,TLR4,and P-P65 proteins(P<0.01).Conclusion NYT decoction can inhibit macrophage M1 polarization through the TREM1/TLR4/NF-κB signaling pathway,improve the inflammation level,and inhibit the formation of ectopic endometrial lesions,thereby preventing postoperative recurrence of EMs.
2.Effects of Netupitant and palonosetron hydrochloride capsules on the pharmacokinetics of albumin-bound paclitaxel in rats under different intestinal microenvironments
Yuanman QIN ; Wenhao CHU ; Jiaqi XU ; Yutong LI ; Bo LIANG ; Xueliang ZHANG ; Jian LIU
China Pharmacy 2025;36(16):1993-1999
OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules (NEPA) on the pharmacokinetics of Paclitaxel for injection (albumin bound) (i. e. albumin-bound paclitaxel) under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group (n=16). Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling, intestinal microbiota diversity was analyzed, and the mRNA expressions of cytochrome P450 3A1 (CYP3A1) and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above (n=16). The normal group was subdivided into the TP chemotherapy group (TP-1 group) and the TP chemotherapy+NEPA group (TP+NEPA-1 group); the model group was subdivided into the TP chemotherapy group (TP-2 group) and the TP chemotherapy+NEPA group (TP+NEPA-2 group) (n=8). Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension (25.8 mg/kg, calculated by netupitant). One hour later, all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard, plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group, the model group showed significantly decreased Chao1 and Shannon indexes (P<0.05), significant alterations in microbiota composition and relative abundance, and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues (P<0.05). Compared with the TP-1 group, the AUC0-t, AUC0-∞, MRT0-t of paclitaxel in the TP-2 group, the cmax, AUC0-t, AUC0-∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged; CL of paclitaxel in the TP-2 group, Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened (P<0.05). Compared with the TP-2 group, cmax of paclitaxel in the TP+NEPA-2 group was significantly increased, and Vd and MRT0-t were significantly decreased or shortened (P<0.05). CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11, leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However, under conditions of intestinal microbiota disorder, concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.
3.Performance evaluation of AI-enabled blood cell morphology system for peripheral blood smear and application in grading screening network of primary medical care system
Xiaobing SUN ; Gusheng TANG ; Kaiying YUAN ; Duanqin DIAO ; Jun HU ; Xiaoyuan SHI ; Hao YUAN ; Anmei WANG ; Yan FANG ; Liqin JIANG ; Xueliang QIN ; Chun XU ; Qi HOU ; Jiong WU
Chinese Journal of Clinical Laboratory Science 2025;43(4):246-252
Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86%,95.16%,and 95.10%,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90%.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59%,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24%,53.39%,and 62.37%for junior technicians,and to 92.06%,83.24%,and 83.12%for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46%,10.61%,and 3.71%for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13%)of red blood cell diseases,5 cases(0.16%)of platelet diseases,2 343 cases(76.90%)of infection-related disea-ses,and 28 cases(0.92%)of malignant hematological diseases.In addition,332 cases(10.90%)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.
4.Analysis of risk factors and development of a nomogram model for early recurrence following curative resection of resectable pancreatic cancer
Chengyu HU ; Jianyu YANG ; Yannan XU ; Yifan YIN ; Minwei YANG ; Xueliang FU ; Dejun LIU ; Yanmiao HUO ; Wei LIU ; Junfeng ZHANG ; Yongwei SUN ; Rong HUA
Chinese Journal of Pancreatology 2025;25(2):104-111
Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.
5.Analysis of risk factors and development of a nomogram model for early recurrence following curative resection of resectable pancreatic cancer
Chengyu HU ; Jianyu YANG ; Yannan XU ; Yifan YIN ; Minwei YANG ; Xueliang FU ; Dejun LIU ; Yanmiao HUO ; Wei LIU ; Junfeng ZHANG ; Yongwei SUN ; Rong HUA
Chinese Journal of Pancreatology 2025;25(2):104-111
Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.
6.Performance evaluation of AI-enabled blood cell morphology system for peripheral blood smear and application in grading screening network of primary medical care system
Xiaobing SUN ; Gusheng TANG ; Kaiying YUAN ; Duanqin DIAO ; Jun HU ; Xiaoyuan SHI ; Hao YUAN ; Anmei WANG ; Yan FANG ; Liqin JIANG ; Xueliang QIN ; Chun XU ; Qi HOU ; Jiong WU
Chinese Journal of Clinical Laboratory Science 2025;43(4):246-252
Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86%,95.16%,and 95.10%,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90%.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59%,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24%,53.39%,and 62.37%for junior technicians,and to 92.06%,83.24%,and 83.12%for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46%,10.61%,and 3.71%for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13%)of red blood cell diseases,5 cases(0.16%)of platelet diseases,2 343 cases(76.90%)of infection-related disea-ses,and 28 cases(0.92%)of malignant hematological diseases.In addition,332 cases(10.90%)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.
7.Risk Factors and Management of Non-curative Endoscopic Resection of Early Gastric Cancer
Chinese Journal of Gastroenterology 2024;29(5):303-307
With the development of endoscopic technology,endoscopic submucosal dissection(ESD)has gradually replaced traditional surgery and emerged as a standard treatment for early gastric cancer.However,in recent years,the number of non-curative resection(NCR)cases has been on the rise.NCR is closely associated with local tumor recurrence,lymph node metastasis,and poor prognosis.Patients with NCR often need to receive additional treatment,thereby increasing the physical and economic burden of the patients.This article reviewed the research progress of the risk factors and management of NCR in early gastric cancer patients treated with ESD,with the aim of providing some reference for the selection of clinical treatment regimens.
8.Early Efficacies of Drainage in Arthroscopic Reconstruction with Anterior Cruciate Ligament Reconstruction
Yuping DUAN ; Hualei ZHAO ; Xueliang FEI ; Yongxin TANG ; Yongsheng XU
Journal of Kunming Medical University 2024;45(1):122-126
Objective To investigate the impact of not using drainage on clinical outcomes after arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction.Methods From March 2022 to June 2023,59 patients undergoing arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction in Lincang People's Hospital were collected and randomly divided into the non-drainage group consisting of 29 cases(observation group)and the 24-hour drainage group consisting of 30 cases(control group).The pain levels of the two groups of patients were recorded on the 1st,3rd,7th,14th,and 30th day after the surgery by using a visual analog scale.Additionally,the knee joint range of motion,length of hospital stay,and occurrence of postoperative complications were monitored.The circumference of the thigh was measured before and after the surgery,and the difference was calculated.Results Repeated measures analysis of variance revealed that there were statistically significant within-subject differences in pain ratings,thigh circumference,and knee joint range of motion(P<0.05),but no statistically significant between-subject differences(P>0.05).Independent samples t-tests showed that on the first day after the surgery,the observation group had lower pain ratings(P<0.001),and higher thigh circumference and knee joint range of motion compared to the control group(P<0.05).There were no statistically significant differences in pain ratings,knee joint range of motion,and thigh circumference between the two groups at the remaining follow-up times(P>0.05);The observation group had a shorter hospital stay than the control group(P<0.001);Both groups of patients had no complications such as lower limb nerve damage,deep vein thrombosis,knee joint infection,or hematomas requiring puncture and aspiration.Conclusion In the early postoperative period following arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,the omission of drainage does not affect the clinical outcomes in terms of pain,knee joint mobility,and thigh circumference.Moreover,omitting drainage reduces the level of pain experienced by patients on the first day after the surgery,improves the knee joint mobility,and decreases the length of hospital stay.Therefore,in arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,it is not recommended to routinely use drainage for preventive purposes.
9.Relationship Between Shunt Grading and Imaging Features in Acute Cerebral Infarction with Right-to-Left Shunt
Yanping LI ; Wei HUANG ; Yu SHEN ; Lijun XU ; Xueliang QI
Chinese Journal of Medical Imaging 2024;32(7):647-652
Purpose To investigate the relationship between imaging characteristics and shunt grading in acute cerebral infarction patients with right-to-left shunt.Materials and Methods The clinical and imaging data of 697 acute cerebral infarction patients who were hospitalized in the Second Affiliated Hospital of Nanchang University from January 2019 to December 2021 were collected,and the patients were divided into right-to-left shunt negative group(443 cases)and right-to-left shunt positive group(254 cases)according bubble test,compared the difference in demographic data and imaging characteristics between the two groups.In the shunt positive group,the imaging characteristics of the two groups of patients and their relationship with the shunt grade were analyzed.Results There were no statistical differences in gender,age,smoking,hyperlipidemia and history of coronary heart disease between the two groups(P>0.05),but there were statistical differences in the history of hypertension(OR=0.533,95%CI 0.380-0.748),diabetes(OR=0.649,95%CI 0.422-0.999)and cerebral infarction(OR=0.275,95%CI 0.136-0.555)(all P<0.05).The imaging characteristics of the two groups of patients showed that there were significant differences in the number of infarct foci(χ2=53.957,4.219;both P<0.05),but there was no statistical difference in the infarct location between the two groups(P>0.05).Among the patients with acute cerebral infarction combined with positive bubble test,the imaging manifestations of grading I and II patients were mainly unilateral anterior circulation or posterior circulation infarction,and deep and single infarction were more common.In patients with grading III and IV shunts,multiple infarcts with combined bilateral anterior and posterior circulations were more common.Conclusion The imaging manifestations of patients with acute cerebral infarction combined with right-to-left shunt have their own characteristics.Bubble test has high sensitivity in the diagnosis of right-to-left shunt.The comprehensive analysis can provide certain guidance for clinical practice.
10.Research on predicting intestinal adverse reactions to chemotherapy drugs using mouse colon organoids
Lei YING ; Xu ENWEI ; Bai ZHONGYUAN ; Kang KEQING ; Bai XUELIANG ; Cui WEI
Chinese Journal of Clinical Oncology 2024;51(9):447-453
Objective:To predict the gastrointestinal side effects of chemotherapeutic drugs using healthy murine colon organoids.It aimed to identify safer alternative treatments for patients intolerant to certain chemotherapy regimens and demonstrate the potential clinical ap-plications of organoids in predicting gastrointestinal side effects.Methods:Healthy mouse colonic crypt cells were cultured in 3D.Paraffin sections of colon tissues and organoids were subsequently prepared,followed by haematoxylin and eosinand immunohistochemical staining(CDX2,Ki67,and CK19).The colonic organoids were treated with five chemotherapeutic drugs,and cell activity was assessed to determine their intestinal toxicity.The consistency of the incidence of gastrointestinal side effects observed in this study and in clinical practice were analyzed by comparing the results to the published literature.Results:The histological characteristics of the colon organoids were highly consistent with those of the original colon tissues.The tolerance of normal colon organoids to different chemotherapeutic drugs was vari-able.Capecitabine had the least cytotoxic effect on mouse colon organoids,whereas paclitaxel liposomes showed the strongest cytotoxic ef-fect when IC50 was the only consideration.Considering clinical drug concentrations,a significant difference was observed in the organoid in-hibition rates between albumin paclitaxel and liposomal paclitaxel.Statistical analysis of clinical trial data showed that the incidence of gradeⅢ/Ⅳ diarrhea caused by albumin paclitaxel,epirubicin,capecitabine,and cyclophosphamide was consistent with the corresponding or-ganoid inhibition rates.Conclusions:Combining clinical drug doses,we recommend prioritizing albumin paclitaxel and avoiding the use of liposomal paclitaxel to improve chemotherapy tolerance.This study demonstrates that normal colon organoids can effectively predict the occurrence of severe diarrhea associated with most chemotherapeutic drugs.

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