Objective:To investigate whether silencing signal transducer and activator of transcription 6 (STAT6) with siRNA can inhibit eosinophilic inflammation of sinonasal mucosa in a mouse model of eosinophilic chronic rhinosinusitis (ECRS).Methods:The study was conducted from March to September in 2022. Forty-eight female BALB/c mice were randomly divided into four groups: the control group, the Vehicle (transfection reagent)-treated group, the Scramble siRNA (Control siRNA)-treated group, and the STAT6 siRNA-treated group, with twelve mice in each group. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was established. SiRNA prepared in Lipofectamine was locally administered to the nasal cavity. After administration, samples of the peripheral blood and sinonasal mucosa were collected. Eosinophils in peripheral blood were detected by hematology analyzer. Total and OVA-specific IgE (OVA-sIgE) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Mucosal levels of cytokines and chemokines, including interleukin (IL)-5, IL-17A, interferon-γ (IFN-γ) and eotaxin-1, were also measured using ELISA. Mucosal histological changes of eosinophil infiltration were examined using hematoxylin, and eosin staining, and tissue eosinophil count was performed using a microscope under a high-power field (HPF). Tissue expression of STAT6 and phosphorylated STAT6 (p-STAT6) was detected with the western blot method. Immunofluorescence staining was used to localize the expression of p-STAT6 in sinonasal mucosa. Statistical analysis was conducted using SPSS 18.0 software.Results:Peripheral blood eosinophil count, percentage of peripheral blood eosinophil, total serum IgE level, and serum OVA-sIgE level in the STAT6 siRNA-treated group [(0.318±0.045)×10 3/μl, (3.667±0.479)%, (102.070±13.205) ng/ml, and (38.870±7.352) ng/ml] were significantly different from those of the Vehicle-treated group [(0.532±0.049)×10 3/μl, (6.710±1.061)%, (203.102±29.653) ng/ml, and (74.575±6.432) ng/ml, Z value was -2.56, -2.24, -2.40, and -2.56, respectively, all P<0.05] and Scramble siRNA-treated group [(0.493±0.036)×10 3/μl, (5.858±0.872)%, (189.964±30.042) ng/ml, and (80.935±8.358) ng/ml, Z value was -2.17, -2.08, -2.24, and -2.72, respectively, all P<0.05]. Besides, IL-5 and eotaxin-1 levels in the STAT6 siRNA-treated group [(312.279±34.281) pg/ml and (25.297±4.323) pg/ml] were significantly lower than those in the Vehicle-treated group [(689.667±31.905) pg/ml and (68.278±6.485) pg/ml, Z value was -2.73 and -2.88, respectively, both P<0.01] and Scramble siRNA-treated group [(661.783±42.094) pg/ml and (63.015±7.416) pg/ml, Z value was -2.72 and -2.81, respectively, both P<0.01]. Tissue eosinophil count in sinonasal mucosa was (29.132±4.163)/HPF in the STAT6 siRNA-treated group, and were significantly less than those in the Vehicle-treated group [(78.050±7.912)/HPF, Z=-2.88, P<0.01] and Scramble siRNA-treated group [(73.864±8.671)/HPF, Z=-2.72, P<0.01]. The expression level of STAT6 protein (0.105±0.021) was significantly decreased in the mice treated with STAT6 siRNA compared with PBS, Vehicle, and Scramble siRNA (0.232±0.037, 0.243±0.039, and 0.228±0.032, Z value was -2.25, -2.49, and -2.56, respectively, all P<0.05). Corresponding, p-STAT6 protein level (0.292±0.038) was markedly decreased by the introduction of STAT6 siRNA, the difference was statistically significant as compared with the Vehicle-and Scramble siRNA-treated groups (0.613±0.046 and 0.641±0.050, Z value was -2.81 and -2.88, respectively, both P<0.01). Immunofluorescence staining showed that p-STAT6 was mainly located in the nucleus of nasal epithelial cells and inflammatory cells. The green fluorescence of p-STAT6 expression in sinonasal mucosa in the STAT6 siRNA-treated group was weaker than that in the Vehicle-and Scramble siRNA-treated groups. Conclusion:Intranasal administration of STAT6 siRNA can significantly downregulate STAT6 expression, decrease p-STAT6 level, and prohibit the development of Th2-skewed ECRS.

Objective:To investigate protective effect of Pinus massoniana needle extract (PMNE) against oxidative stress in human dermal papilla cells (HDPC) , and to explore its mechanisms. Methods:As research objects, some cultured HDPC were treated with H 2O 2 at different concentrations of 0 (control group) , 0.1, 0.2, 0.4, 0.8 and 1.0 mmol/L, in order to establish the optimal condition for in vitro oxidative stress in HDPC; some other HDPC were transfected with nuclear factor-erythroid 2-related factor 2 (Nrf2) specific small interfering RNAs (siRNA1, siRNA2, siRNA3) or a Nrf2-overexpressing plasmid (pCMV6-XL5-Nrf2) , the HDPC transfected with a scrambled-siRNA and an empty plasmid pCMV6-XL5 served as the control siRNA group and control plasmid group respectively, and HDPC subjected to conventional culture served as the blank group; after the above treatment, real-time fluorescence-based quantitative PCR and Western blot analysis were performed to determine Nrf2 mRNA and protein expression, respectively; cell viability and apoptosis were detected in the above transfected cells after the treatment with H 2O 2 at an optimal concentration. In the subsequent experiment, some HDPC were divided into several groups: control group subjected to conventional culture, dihydrotestosterone group treated with 0.03 μg/ml dihydrotestosterone, proanthocyanidin group treated with 0.03 μg/ml dihydrotestosterone and 6.00 μg/ml proanthocyanidin B2, PMNE groups treated with 0.03 μg/ml dihydrotestosterone and PMNE at different concentrations of 1, 5, 25 and 100 μg/ml; after the above treatment, cell viability and apoptosis were detected, relative fluorescence intensity of intracellular reactive oxygen species (ROS) , malondialdehyde (MDA) content, mRNA and protein expression of Nrf2, quinone oxidoreductase 1 (NQO1) , heme oxygenase 1 (HO-1) , Kelch-like ECH-related protein 1 (Keap1) , transforming growth factor (TGF) -β1, Sma- and Mad-related protein 2/3 (Smad2/3) , phosphorylated Smad2/3 (p-Smad2/3) were determined in HDPC. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference- t test for multiple comparisons. Results:The viability of HDPC ranged from 75% to 85% after the treatment with 0.4 mmol/L H 2O 2, which was selected as the optimal condition for in vitro oxidative stress in HDPC. Compared with the blank group and control siRNA group, the Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups showed significantly decreased Nrf2 mRNA and protein expression (all P < 0.05) , but significantly increased apoptosis rate (Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups, blank group and control group: 12.50% ± 0.05%, 26.07% ± 0.05%, 58.44% ± 1.03%, 10.38% ± 0.64%, 13.05% ± 0.12%, respectively; all P < 0.05) . Nrf2 protein expression was the lowest in the Nrf2-siRNA2 group, so Nrf2-siRNA2 was selected as the optimal interfering fragment for subsequent experiments. Compared with the blank group and control plasmid group, the Nrf2 overexpression group showed significantly increased Nrf2 mRNA and protein expression (both P < 0.05) , but a significantly decreased apoptosis rate (all P < 0.05) . After the treatment with 0.4 mmol/L H 2O 2, the Nrf2 overexpression group showed a significantly decreased apoptosis rate, but significantly increased cell viability compared with the empty vector group ( t = 3.66, 40.40, respectively, both P < 0.001) ; the Nrf2-siRNA2 group showed a significantly increased apoptosis rate, but significantly decreased cell viability compared with the control group ( t = 13.13, 67.37, respectively, both P < 0.001) . In the PMNE treatment experiment, the proanthocyanidin group and PMNE groups showed significantly increased cell viability, but significantly decreased apoptosis rates compared with the dihydrotestosterone group (all P < 0.01) ; proanthocyanidin and PMNE at different concentrations could significantly inhibit dihydrotestosterone-induced overexpression of ROS and MDA in HDPC (all P < 0.01) ; the protein expression of Nrf2, NQO1 and HO-1 was significantly higher in the proanthocyanidin group, 5-, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) , while the protein expression of Keap1 and TGF-β1, and the Smad2/3 phosphorylation level were significantly lower in the proanthocyanidin group, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) . Conclusion:Nrf2 plays an important role in protecting against oxidative damage in HDPC, and PMNE may exert marked protective effect on HDPC by activating the Nrf2-antioxidant responsive element signaling pathway.

Objective:To investigate the clinicopathologic features and prognosis of breast mucosa associated lymphoid tissue(MALT) lymphoma.Methods:Clinical data of 8 breast MALT lymphoma patients were retrospectively analyzed at Tianjin Medical University Cancer Institute and Hospital from Jan 1, 2004 to Jan 31, 2017.Results:All were females, median age was 50 years. Tumors were located in the left breast in 3 cases while 5 cases in the right. All tumors were single in the outer-upper 1/4 quadrant of the breast. By Ann Arbor clinical stageⅠ, Ⅱ, Ⅲ and Ⅳ were 3, 2, 1 and 2, respectively. None of patients had B symptoms. 7 cases underwent surgery.All of the 8 cases received chemotherapy, 6 cases had complete response, one partial response, one with stable in efficacy evaluation. The follow-up time was 2-154 months. The 1, 3, 5-year overall survival rate were 100.0%, 50.0%, 50.0%, median survival time was 144.00 months. The 1-year progress free survival rate was 78.0% and median progress free survival time 28.29 months.Conclusion:Breast MALT is extremely rare without specific clinical features. Almost all are single tumors without B symptom. It′s sensitive to chemotherapy and the patients have fair prognosis.

Objective: To evaluate the relationships between admission fasting serum C-peptide concentration and cardiac function status in chronic heart failure (CHF) patients with or without diabetes. Methods: From July 2017 to December 2018, 262 CHF patients with or without diabetes in the Department of Cardiology of Pudong hospital in Shanghai were analyzed.Their cardiac function was classified as New York Heart Association (NYHA) grade Ⅱ to Ⅳ, and they were divided into diabetes group (80 cases) and non diabetes group (182 cases). At the same time, 62 subjects without diabetes and heart disease were randomly selected as the control group.To analyze the relationship between fasting serum C-peptide level and cardiac function in diabetic and nondiabetic CHF patients. Results: (1)The fasting plasma glucose and serum C-peptide concentrations of diabetes group paitents were(8.7±2.9) mmol/L and(0.78±0.67) nmol/L respectively, the nondiabetes group paitents were(5.8±1.67) mmol/L and(0.56±0.61)nmol/L respectively, the control group were(5.1±0.69) mmol/L and(0.16±0.12)nmol/L respectively.The difference in the three groups was statistically significant(all P<0.001). The levels of fasting blood glucose and serum C-peptide in diabetic group were significantly higher than those in non diabetic group and control group (all P<0.01). The levels of fasting blood glucose and serum C-peptide in non diabetic group were significantly higher than those in control group (P<0.05 or P<0.01). The left ventricular ejection fraction (LVEF) in diabetic group was(44.1±8.3)%, and those in non diabetic group and control group were(46.7±7.2)% and(64.8±3.8)%.The difference in the three groups was statistically significant(<0.001). The LVEF of diabetic group was significantly lower than that of non diabetic group and control group (all P<0.01), and the CRP of diabetic group was (1.39±0.91) mg/L, the N-terminal pro-B-type natriuretic peptide (pro-BNP) was (1 771.3±23.1) ng/L, the hemoglobin was (125.6±16.7) g/L in the diabetic group, and (1.22±0.73) mg/L, (1 659.2±19.3) ng/L, (126.1±16.5) g/L in the non diabetic group, respectively, and (0.85±0.72) mg/L, (87.2±17.2) ng/L, (136.4±15.2) g/L in the control group, respectively.The differences among the three groups were statistically significant (P<0.001). CRP and pro-BNP in the diabetic group and non diabetic group were significantly higher than those in the control group (all P<0.01), and hemoglobin levels were significantly lower than those in the control group(all P<0.01). There were no statistically significant differences in CRP, pro-BNP and hemoglobin between the diabetic group and non diabetic group (all P>0.05). (2) In all patients with heart failure, diabetes mellitus and non diabetes heart failure, the levels of serum C-peptide were (1.05±0.85), (1.17±0.82), (0.99±0.86) nmol/L in NYHA Ⅳ group, and (0.53±0.22), (0.52±0.20), (0.54±0.23) nmol/L in NYHA Ⅲ group, and (0.32±0.09), (0.32±0.11), (0.31±0.09) nmol/L in NYHA Ⅱ group.After adjustment of age, gender, smoking, insulin secretion and hypoglycemic drugs, body mass index, blood pressure, total bilirubin (TBIL), alanine aminotransferase (ALT), creatinine, blood glucose, blood lipid, white blood cell count (WBC) and hemoglobin level by covariance analysis, all patients with heart failure The level of serum C-peptide in NYHA Ⅳ group was significantly higher than that in Ⅲ group (all P<0.01) and Ⅱ group (all P<0.01). In all patients with heart failure and non diabetic heart failure, the level of serum C-peptide in NYHA Ⅲ group was significantly higher than that in Ⅱ group (all P<0.05). There was no significant difference in serum C-peptide between all patients with heart failure, diabetes mellitus and non diabetes heart failure (all P>0.05) (3) Using multiple linear regression analysis, the adjustment factors included age, gender, smoking, BMI, blood pressure, TBIL, alt, creatinine, blood glucose, blood lipid, WBC and hemoglobin levels.The results showed that the serum C-peptide level was positively correlated with pro-BNP in all patients with heart failure, diabetes and non diabetes heart failure (β: 0.006, 95%CI -0.016-0.028 , P=0.007; β: 0.117, 95%CI-0.042-0.277 , P=0.006; β: 0.411, 95%CI-0.149-0.971 , P=0.023), negatively correlated with LVEF(β: -0.122, 95%CI-0.285-0.041, P=0.004; β: -0.008, 95%CI-0.032-0.016, P=0.010; β: -0.065, 95%CI-0.139-0.011, P=0.036). Conclusion The level of fasting serum C-peptide was significantly increased in patients with CHF and non-diabetic patients, and was related to the severity of heart failure.

Objective: To investigate the clinical characteristics, therapy modality and prognosis of primary breast diffuse large B-cell lymphoma(PB-DLBCL). Methods: A total of 68 patients with PB-DLBCL treated in Tianjin Medical University Cancer Institute and Hospital were enrolled between January 1, 2004 and January 31, 2017. Clinicopathological data were retrospectively analyzed. 67 patients were female and only one male. The median age was 56 years old. 46 patients had Ann Arbor clinical stageⅠ~Ⅱ disease, and the other 22 were stage Ⅲ~Ⅳ. The patients with and without B symptom were 11 and 57, respectively. Kaplan-Meier method was used for univariate analysis to calculate the 5-year overall survival (OS) rate and 5-year progress-free survival (PFS) rate, compared using the log rank test. Cox regression analysis was used for multivariate analysis. Results: The 1, 3, 5-year OS rate were 84.0%, 78.0% and 73.0%, and 1, 3, 5-year PFS rate were 80.0%, 71.0% and 51.0%, respectively. Univariate analysis indicated that eastern cooperative oncology group (ECOG) score, Ann Arbor clinical stage, international prognostic index (IPI) score, risk stratification, B symptom, β2-microglobulin(β2-MG) level, size of the tumor and cycles of chemotherapy were prognostic factors for OS (all P<0.05), and Ann Arbor clinical stage, IPI score, risk stratification and B symptom were prognostic factors for PFS (all P<0.05). Multivariate analysis indicated that Ann Arbor clinical stage was independent prognostic factor for OS(P=0.029) and B symptom was independent prognostic factor for PFS(P=0.028). Conclusions Prognosis of PB-DLBCL was relatively good. Ann Arbor clinical stage and B symptom were independent prognostic factors for OS and PFS, respectively.

Objective To investigate the clinical characteristics, therapy modality and prognosis of primary breast diffuse large B?cell lymphoma ( PB?DLBCL). Methods A total of 68 patients with PB?DLBCL treated in Tianjin Medical University Cancer Institute and Hospital were enrolled between January 1, 2004 and January 31, 2017. Clinicopathological data were retrospectively analyzed. 67 patients were female and only one male. The median age was 56 years old. 46 patients had Ann Arbor clinical stageⅠ～Ⅱdisease, and the other 22 were stage Ⅲ～Ⅳ. The patients with and without B symptom were 11 and 57, respectively. Kaplan?Meier method was used for univariate analysis to calculate the 5?year overall survival (OS) rate and 5?year progress?free survival (PFS) rate, compared using the log rank test. Cox regression analysis was used for multivariate analysis. Results The 1,3,5?year OS rate were 84.0%, 78.0% and 73.0%,and 1,3,5?year PFS rate were 80.0%,71.0% and 51.0%, respectively. Univariate analysis indicated that eastern cooperative oncology group ( ECOG) score, Ann Arbor clinical stage, international prognostic index (IPI) score, risk stratification, B symptom, β2?microglobulin(β2?MG) level, size of the tumor and cycles of chemotherapy were prognostic factors for OS (all P＜0.05), and Ann Arbor clinical stage, IPI score, risk stratification and B symptom were prognostic factors for PFS (all P＜0.05). Multivariate analysis indicated that Ann Arbor clinical stage was independent prognostic factor for OS(P＝0.029) and B symptom was independent prognostic factor for PFS(P＝0.028). Conclusions Prognosis of PB?DLBCL was relatively good. Ann Arbor clinical stage and B symptom were independent prognostic factors for OS and PFS, respectively.

Objective To investigate the clinical characteristics, therapy modality and prognosis of primary breast diffuse large B?cell lymphoma ( PB?DLBCL). Methods A total of 68 patients with PB?DLBCL treated in Tianjin Medical University Cancer Institute and Hospital were enrolled between January 1, 2004 and January 31, 2017. Clinicopathological data were retrospectively analyzed. 67 patients were female and only one male. The median age was 56 years old. 46 patients had Ann Arbor clinical stageⅠ～Ⅱdisease, and the other 22 were stage Ⅲ～Ⅳ. The patients with and without B symptom were 11 and 57, respectively. Kaplan?Meier method was used for univariate analysis to calculate the 5?year overall survival (OS) rate and 5?year progress?free survival (PFS) rate, compared using the log rank test. Cox regression analysis was used for multivariate analysis. Results The 1,3,5?year OS rate were 84.0%, 78.0% and 73.0%,and 1,3,5?year PFS rate were 80.0%,71.0% and 51.0%, respectively. Univariate analysis indicated that eastern cooperative oncology group ( ECOG) score, Ann Arbor clinical stage, international prognostic index (IPI) score, risk stratification, B symptom, β2?microglobulin(β2?MG) level, size of the tumor and cycles of chemotherapy were prognostic factors for OS (all P＜0.05), and Ann Arbor clinical stage, IPI score, risk stratification and B symptom were prognostic factors for PFS (all P＜0.05). Multivariate analysis indicated that Ann Arbor clinical stage was independent prognostic factor for OS(P＝0.029) and B symptom was independent prognostic factor for PFS(P＝0.028). Conclusions Prognosis of PB?DLBCL was relatively good. Ann Arbor clinical stage and B symptom were independent prognostic factors for OS and PFS, respectively.

Objective To evaluate the efficacy and safety of suctioning flexible ureteroscopy with automatic control of renal pelvic pressure in the treament of intrarenal and proximal ureteral stones.Methods From November 2014 to December 2016,a total of 372 patients,including 200 males and 172 females,with upper urinary tract calculi were studied.The average age of patients was 48.1 years old.The average size of stone was 5-35mm,mean 15.7mm.There were 272 cases of renal calculi,80 cases of ureteral calculi and 20 cases of renal calculi combined with ureteral calculi.There were 252 cases of single calculi and 127 cases of multiple calculi.There were 237 cases of urinary tract infection and 14 cases of bacteremia.All patients were treated by suctioning fiexible uretemscopy with automatic control of renal pelvic pressure by a patented intelligent system including an irrigation and suctioning platform and a ureteral access sheath with a pressuresensitive tip.Statistical analysis was performed regarding renal pelvic pressure,operative time,stone-free rates,and complications.Results Three hundred and thirty of 372 patients only accepted one surgery to remove the stone.There were 12 cases of upper ureteral calculi were converted to ureteroscope lithotripsy.Seventeen cases were converted to percutaneous nephrolithotomy due to significant ureteral stenosis.Seven cases who failed the first surgery due to difficulty in placing the ureteral access sheath but flexible ureteroscopy were successfully performed in these patients after indwelling a D-J stent for 2 weeks.No stone was found in 6 cases,and the soft endoscope of ureter was examined.In all patients,the renal pelvic pressure of the pelvis was controlled within 20 mmHg.The average operative time was 15-180 min(mean 58.9 min).The stone-free rates was 95.55％ (322/337),the incidence of postoperative fever was 2.97％ (10/337),the sepsis rate was 1.19％ (4/337),the incidence of urinary sepsis was 0.89％ (3/337),the incidence of lumbago caused by extravasation was 0.59％ (2/337),and no peripheral viscera injury or death case.There was no statistically significant difference between preoperative and postoperative white and red blood cells (P ＞ 0.05).Conclusions This new type of suctioning flexible ureteroscopy with intelligent pressure-control has the advantages of perfusion attraction,pressure feedback,intelligent control and visualization of intracavity pressure.It could be a new type of operation with high safety,low complication and high stone free rate.

Objective To investigate the recurrence and risk factors of gastric high-grade intraepithelial neoplasia(HGIN)and early gastric cancer(EGC)after endoscopic submucosal dissection (ESD). Methods The clinical and follow-up data on 444 patients(451 lesion)with HGIN and EGC undergoing ESD in Digestive Endoscopy Center of Chinese PLA General Hospital from November 2006 to January 2016 were summarized, and the risk factors of recurrence were analyzed. Results A total of 410 patients were followed-up, and the recurrence rate was 3.2%(13 patients, 13 lesions), with mean recurrence time of 17.6±9.6 months(6-38 months). Univariate and multivariate analysis revealed that the size of the lesion>4.0 cm was the only risk factor of recurrence(P=0.012,OR=10.855,95%CI:1.673~70.442). Conclusion The rate of recurrence is increasing with the EGC extending, therefore, postoperative monitoring should be strengthened to patients with larger lesion.

Objective: To evaluate the effect of acrylamide on the apoptosis of nerve cells by integral cell modelling in vitro which simulates the barrier effect and metabolic micro-environment. Methods: A non-contact and co-cultured in vitro blood brain barrier (BBB) model was established by using human umbilical vein endothelial cells (HUVEC) and rat glioma cells (C6) . The trans-endotheilal electrical resistance (TEER) and horseradish peroxidase (HRP) tracer effects were measured to verify the tight connectivity and permeability of the established BBB model. An integrate discrete multiple organ cell co-culture (idMOC) model was established by inoculating the human renal cortical proximal tubular epithelial cells (HK-2) , human normal hepatocytes (L-02) and human neuroblastoma cells (SH-SY5Y) into the self-made multi-organ plate for co-culturing. Then the model was verified by observing the growth curve of various tissue cells under co-culturing or culturing individually. SH-SY5Y cells were exposed to different concentrations of acrylamide directly and indirectly (through BBB model and idMOC model) . The changes of cell apoptosis rate were analyzed by flow cytometry to explore the impact of model on Acrylamide (ACR) injury of typical neurotoxic agents. Results: HUVEC cells can form a wide range of close-connected complex and then inhibit the external electric field under the cross-endothelial movement, and the mean was lower than that of endothelial cell culture group at 4, 5 and 6 days (P<0.05) ; After 20 min, the penetration rate of HRP in the co-culture group was less than that in the individual culture group, and the difference was statistically significant (P<0.05) , indicating that the barrier function of the co-culture group was higher than that of the individual culture group. All cells can exchange substances through the exchange hole of the culture plate, the cells grow well and there was no obvious death. The growth curve in individual culture group and co-culture group were basically the same, the difference was not statistically significant (P>0.05) . Under the condition of different concentrations of ACR (140, 270 g/ml) , compared with the direct exposure group, the apoptosis rate of the BBB model and the idMOC model were significantly decreased, and the difference was statistically significant (P<0.05) . Conclusion Based on HUVEC cells and C6 cells co-culture system, a blood-brain barrier model in vitro was established and based on co-culture of HK-2, L-02 and SH-SY5Y, the idMOC model was established. The toxicity and toxic action characteristics of ACR on SH-SY5Y cells were evaluated by validation tests.