1.Pathogen distribution and predictive nomogram for postoperative nosocomial infection in rectal cancer
Bowen CHEN ; Jin ZHAO ; Xiaoxia WEI ; Lü MING ; Shengjun GAN ; Yuhua YUAN
Journal of Chongqing Medical University 2025;50(3):352-358
Objective:To examine the distribution of pathogens that cause postoperative nosocomial infections in patients with rectal cancer(RC)and to construct a predictive nomogram for nosocomial infection.Methods:The clinical data of 1537 RC patients admitted to Sir Run Run Shaw Hospital between January 2021 and December 2022 were collected.Patients were assigned 1∶1 by propensity score matching(PSM)to the infection group(n=83)and control group(n=83)based on the occurrence of nosocomial infection.The dis-tribution and drug resistance of bacteria in patients with nosocomial infection were analyzed.Risk factors for postoperative nosocomial infection were identified by least absolute shrinkage and selection operator(LASSO)regression,and a predictive nomogram was con-structed using multivariate logistics regression.The predictive performance of the model was evaluated by receiver operating character-istic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results:A total of 93 strains of pathogens were isolated from the 83 infected patients,including 62 strains of Gram-negative bacteria(66.67%;predominantly Escherichia coli and Pseudomonas ae-ruginosa),25 strains of Gram-positive bacteria(26.88%;mainly Enterococcus faecalis),and 6 strains of fungi(6.45%;all Candida albicans).LASSO and multivariate logistics regression showed that smoking(odds ratio[OR]=3.97,95%CI=1.27-12.43),the dwelling time of drainage tube(OR=1.19,95%CI=1.08-1.30),difference in preoperative and postoperative neutrophil counts(OR=1.23,95%CI=1.01-1.49),and difference between preoperative and postoperative C-reactive protein levels(OR=1.05,95%CI=1.03-1.07)were inde-pendent risk factors for postoperative nosocomial infection in RC patients.The area under the ROC curve of the nomogram constructed based on the above factors was 0.933(95%CI=0.896-0.969).The calibration curve showed that the predicted risk was in good agree-ment with the actual observed risk of infection.In addition,DCA demonstrated that the nomogram has good clinical utility and high net clinical benefits in predicting nosocomial infection.Conclusion:The nomogram constructed in this study has a good predictive perfor-mance in postoperative nosocomial infection in RC patients.
2.Prognostic value of peripheral blood NLR and TrxR expression in ovarian cancer patients receiving immunotherapy
Qiumei JIN ; Xiaoli CAO ; Yifeng GU ; Xiaoxia ZHANG ; Yujie LI
International Journal of Laboratory Medicine 2025;46(6):714-718
Objective To investigate the prognostic value of peripheral blood neutrophil-lymphocyte ratio(NLR)and thioredoxin reductase(TrxR)in patients with ovarian cancer receiving immunotherapy.Methods A total of 109 patients with advanced ovarian cancer treated in the Tumor Hospital Affiliated to Nantong University from January 2021 to December 2021 were selected as the research objects.The levels of NLR and TrxR in peripheral blood before immunotherapy were detected,and the evaluation value of NLR and TrxR on short-term efficacy,progression-free survival(PFS)and overall survival(OS)in ovarian cancer pa-tients receiving immunotherapy was explored.Results The optimal cut-off values of TrxR and NLR were 4.97 U/mL and 2.49%,respectively.According to the optimal cut-off value of TrxR and NLR,the patients were divided into the high level of TrxR group(69 cases,≥4.97 U/mL)and the low level of TrxR group(40 cases,<4.97 U/mL),the high level of NLR group(72 cases,≥2.49%)and the low level of NLR group(37 cases,<2.49%).The objective response rate(ORR)of the high level of NLR group was lower than that of the low level NLR group(P<0.05),and the disease progression rate(DPR)was higher than that of the low NLR group(P<0.05).The high level of TrxR group had a significantly lower ORR and a significantly higher DPR than the low level of TrxR group(P<0.05).The median PFS and OS of the high level of NLR group were 15.0 months and 16.0 months,respectively.The median PFS and OS of the low level of NLR group were 19.0 months and 21.0 months,respectively.The median PFS and OS of the high level of TrxR group were 15.0 months and 17.0 months,respectively.The median PFS was 18.0 months and the median OS was 21.0 months in the low level of TrxR group.NLR and TrxR were the influencing factors of PFS and OS in pa-tients with ovarian cancer immunotherapy(P<0.05).Conclusion The levels of NLR and TrxR in peripheral blood can be used as important prognostic indicators for advanced ovarian cancer patients receiving immuno-therapy.The lower the levels of NLR and TrxR,the better the prognosis of ovarian cancer patients.
3.Inhibitory effect of MKK6(E)fusion protein on the growth of ovarian cancer graft tumors in nude mice by regulating the p38/ATF-2 pathway
Jin YUAN ; Jiali KANG ; Xiaoxia WANG
International Journal of Laboratory Medicine 2025;46(11):1302-1308
Objective To investigate the inhibitory effect of MKK6(E)fusion protein on the growth of o-varian cancer graft tumors in nude mice and its possible mechanism.Methods A subcutaneous transplantation tumor model in nude mice was constructed using subcutaneous injection of human ovarian cancer HO8910PM cells,which were divided into model group,paclitaxel(positive control,3 mg/mL)group,MKK6(E)fusion protein(1.2 mmol/L)group and MKK6(E)fusion protein+SB202190(p38 agonist,10 μmol/L)group by numerical randomization table,each with 6 animals.The drug was administered continuously in the tail vein for 21 d,once every 3 d.At the end of the administration,the tumor was exfoliated and the tumor volume,mass and tumor inhibition rate were calculated.Serum carbohydrate antigen(CA)125 level was detected by enzyme linked immunosorbent assay(ELISA),histopathology of the tumor was detected by HE staining,and apoptosis of the tumor cells was detected by TUNEL staining.In addition,expression of Fibronectin,matrix metallo-peptidase(MMP)2,and MMP9 were detected by immunohistochemistry,apoptosis and the p38/ATF-2 pathway-related proteins were detected by Western blot.Results Compared with the model group,the tumor volume,mass and serum CA125 level of nude mice in the paclitaxel group and the MKK6(E)fusion protein group were reduced,the tumor suppression rate and the apoptosis rate of cancer cells were increased,the volume of cancer cells in the transplanted tumor tissue was reduced,the nucleus was lightly stained,the di-viding heterogeneity was reduced compared with that of the model group,and the large area of lamellar nec-rotic zone and apoptotic cells were seen,and the expression of Fibronectin,MMP2 and MMP9 was reduced.Bax and Cleaved caspase 3 expression was up-regulated,and Bcl-2 expression and phosphorylated p38(p-p38)/p38 and p-ATF-2/ATF-2 were down-regulated(P<0.05).Compared with the MKK6(E)fusion pro-tein group,nude mice in the MKK6(E)fusion protein+SB202190 group showed increased tumor volume,mass and serum CA125 levels,decreased tumor suppression and cancer cell apoptosis,better cancer cell status,decreased necrotic areas,increased expression of Fibronectin,MMP2 and MMP9,and down-regulated Bax and Cleaved caspase 3 expression was down-regulated,and Bcl-2 expression and p-p38/p38 and p-ATF-2/ATF-2 were up-regulated(P<0.05).While p-ERK/ERK and p-JNK/JNK were compared among the 4 groups,the difference was not statistically significant(P>0.05).Conclusion MKK6(E)fusion protein inhibits the growth of ovarian cancer subcutaneous graft tumors,and its mechanism may be related to the inhibition of p38/ATF-2 signa-ling pathway activation.
4.Expression of COA6 in breast cancer and its correlation with tumor immune cell infiltration
Xiaoxia JIN ; Yushan LIU ; Jiping HU ; Xinghua ZHU
Basic & Clinical Medicine 2025;45(6):755-761
Objective To detect the expression of cytochrome c oxidase assembly factor 6(COA6)in breast cancer,study its clinical significance,and analyze the effect of COA6 on immune infiltration in breast cancer.Methods Differential genes were screened by the whole transcriptome sequencing and the expression of COA6 was explored with TCGA(The Cancer Genome Atlas Program)database.The tissues of 125 breast cancer and adjacent tissues were stained by immunohistochemistry to detect COA6 protein expression and analyze the correlation with clinical features.The COA6 mRNA and protein expression in breast cancer cells and tissues were determined by qRT-PCR and Western blot,respectively.The TIMER(Tumor Immune Estimation Resource)database was used to analyze the correlation between high COA6 gene expression and immune cell infiltration.Results The positive expression rate of COA6 in breast cancer tissues was 88%(110/125),which was higher than that of paracarinoma tissues(7.2%,9/125)(P<0.05)and was positively correlated with tumor size and histological grade.In fresh breast cancer tissues,COA6 protein expression was significantly higher than that in adjacent tissues.Both COA6 mRNA and protein expression were significantly increased in the breast cancer cell lines.COA6 was positively cor-related with the infiltration of helper T cells,NK cells,CD8+T cells,M1 type macrophages,regulatory T cells,dendritic cells,and memory CD4+T cells in the tumor microenvironment.Conclusions The expression level of COA6 is increased in breast cancer and is positively correlated with tumor immune infiltration,which provides a po-tential therapeutic target for breast cancer treatment.
5.Analysis of the risk factors for catheter-related thrombosis in upper arm infusion port and construction of machine-learning prediction model
Mengsu ZHANG ; Jie ZHANG ; Guangxin JIN ; Xiaoxia QIU ; Xuebin ZHANG ; Jun BU
Journal of Interventional Radiology 2025;34(3):253-260
Objective To analyze the risk factors for catheter-related thrombosis(CRT)in the upper arm infusion port(UAP)and to construct a machine-learning prediction model.Methods A total of 6028 patients,who received UAP implantation at Shanghai Renji Hospital of China from February 2014 to February 2023,were enrolled in this study.The patients were divided into training set(n=4 219)and validation set(n=1 809).Six machine-learning prediction models,including Least Absolute Shrinkage and Selection Operator(LASSO)regression,random forest,decision tree,neural network,XGBoost and logistic,were constructed,and the model having best performance was selected as the optimal model.SHapely Additive exPlanations(SHAP)analysis was used to explain the neural network model,and DALEXtra package was used to explain the continuous variables.Results The neural network model was chosen as the final model.The variables,in order of the degree of importance from high to low,included sex,the diameter of catheter,catheter tip confirmation method,the length of catheter,inpatient or outpatient status,history of central venous catheter implantation,the length of subcutaneous tunnel,age,body mass index(BMI),primary tip displacement,and left or right venous approach.The learning curve,i.e.the area under curve(AUC)of the receiver operating characteristic(ROC)curve,for the training set was>0.6,and the Delong testing and Bootstrap Methods Test showed that the neural network model performed well(P<0.05).The Kolmogorov-Smirnov plot(KS plot)value was 0.313 5,indicating that the model had the good ability of discrimination.The clinical impact curve(CIC)assessment revealed that the model had good clinical value.Conclusion The machine-learning prediction model of upper arm infusion port with CRT has been successfully constructed.For minimizing the risk of CRT,it is recommended to prioritize the use of 5 F diameter catheters,adopt left-sided venous approach and positioning the tip of the catheter based on anatomical measurements,besides,the catheter length should be not shorter than 36.56 cm,and the subcutaneous tunnel length should not be less than 5 cm.The basic features associated with higher CRT risk include age of 50-65 years,BMI being between 18.69 kg/m2 and 20.81 kg/m2 or between 23.68 kg/m2 and 23.94 kg/m2 and male.
6.Effects of early-life 6:2 Cl-PFESA exposure on hippocampal AMPA receptor gene expression in offspring mice
Ruiwen WANG ; Yaping YAO ; Jingshuang CAI ; Fulin QU ; Xiaoxia JIN
Journal of Environmental and Occupational Medicine 2024;41(5):552-559
Background The compound 6:2 chlorinated polyfluorinated ether sulfonic acids (6:2 Cl-PFESA) has been demonstrated abilities of strong bioaccumulation and placental barrier penetration, and it can also cross the blood-brain barrier. However, the mechanism of its neurodevelopmental toxicity in offspring induced by early-life exposure is still unknown. Objective To explore effects of 6:2 Cl-PFESA on the growth and the α-amino-3-hydroxy-5-methylisoxazole-4-propionic (AMPA) receptor gene expression in the hippocampus of offspring mice by establishing a 6:2 Cl-PFESA exposure animal model. Methods Thirty Kunming pregnant mice were randomly divided into five groups: control group, and 2, 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups. The treatment groups were exposed to designed doses of 6:2 Cl-PFESA through drinking water from the first day of gestation until the end of lactation. The pups were weaned on postnatal day (PND) 21, and continued to be exposed to 6:2 Cl-PFESA through drinking water. Birth weight and body length of the offspring were recorded. Offspring mice were anesthetized and sacrificed respectively on PND7, PND21, and PND35, then their hippocampus was peeled from harvested brain tissue. The ultrastructure of hippocampus was observed via transmission electron microscopy; and the expression of AMPA receptors GluR1, GluR2, and GluR3 in the hippocampus was evaluated by real-time reverse transcription polymerase chain reaction. The learning and memory ability of the PND35 mice was measured by Morris water maze test before they were sacrificed. Results The birth weights and the lengths of the pups in the 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups were (2.23±0.36), (1.92±0.20), (1.88±0.31) g, and (33.73±0.98), (32.91±1.30), (32.52±2.07) mm, respectively, which were lower than those in the control group, (2.78±0.35) g and (36.46±2.34) mm (P<0.05), respectively. The results of Morris water maze showed that the escape latencies in the orientation navigation experiment on the 4th day in the 250 μg·L−1 6:2 Cl-PFESA exposure group and on the 5th day in the 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups were longer than those in the control group (P<0.05). In the space exploration experiment, the times of crossing platform in the 50 and 250 μg·L−1 6:2 Cl-PFESA exposure groups were decreased when compared with the control group (P<0.05), and the time of staying in the target quadrant of the 250 μg·L−1 6:2 Cl-PFESA exposure groups were also decreased (P<0.05). Via transmission electron microscopy, compared with the control group, the postsynaptic density was decreased and the synaptic cleft width was widened on PND35 in the 250 μg·L−1 6:2 Cl-PFESA exposure group. The mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups exposed to 250 μg·L−1 6:2 Cl-PFESA during different developmental stages were significantly lower than those in the control group (P<0.05). Except for the 2 μg·L−1 6:2 Cl-PFESA exposure group on PND7, the 6:2 Cl-PFESA exposure inhibited the mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups at different developmental stages (P<0.05). Among them, the 6:2 Cl-PFESA exposure during early development resulted in the highest decrease in the expression levels of GluR1 and GluR2 mRNA in the hippocampus of pups on PND7; GluR3 mRNA expression level in the hippocampus of the exposed pups on PND21 showed the maximum inhibitory effect; the expression levels of GluR1, GluR2, and GluR3 mRNA all showed the least decrease in the hippocampus of the exposure groups on PND35. Conclusion Early-life exposure to 6:2 Cl-PFESA may affect the growth and development of offspring mice, alter the hippocampal synaptic structure, and influence the learning and memory abilities, which may be related to their inhibitory effects on the expression levels of AMPA receptor subunits GluR1, GluR2, and GluR3 genes in the hippocampus of offspring mice at various developmental stages.
7.Clinical application of enhanced recovery after surgery combined with intestinal fluid reflux in enterostomy in newborn
Wenyue LIU ; Xiaoxia WU ; Hui ZHANG ; Xue SUN ; Baohong ZHAO ; Yuanyuan JIN ; Hongxia REN
Chinese Journal of Neonatology 2024;39(3):145-149
Objective:To study the clinical value of enhanced recovery after surgery(ERAS) strategy combined with early intestinal fluid reinfusion among neonates receiving jejunostomy due to intestinal obstruction.Methods:From December 2018 to December 2022, neonates with intestinal obstruction receiving jejunostomy in the Department of Neonatal Surgery of our hospital were prospectively enrolled. They were randomly assigned into ERAS group and traditional treatment (TT) group after surgery. The ERAS group was treated with ERAS strategy plus early intestinal fluid reinfusion. The TT group was treated with conventional gastrointestinal decompression, analgesia as needed and enteric fluid reinfusion according to the amount of defecation. The postoperative parenteral nutrition (PN) duration (T pn), central venous catheter (CVC) duration (T cvc), daily weight gain, duration of postoperative hospital stay (T hos), complications and readmission rate within 30 days were compared between the two groups. Results:A total of 22 cases were included in the ERAS group and 20 cases were in the TT group. T pn [(22.6±9.4) d vs. (30.7±11.3) d], T cvc [(5.9±0.8) d vs. (9.9±2.1) d] and T hos [(26.8±9.8) d vs. (33.8±11.5) d] in the ERAS group were significantly shorter than the TT group ( P<0.05). No significant difference existed in daily weight gain between the two groups ( P>0.05). The incidence of postoperative gastrointestinal mucosal bleeding in the ERAS group was significantly lower than the TT group (13.6% vs. 45.0%)( P<0.05). No significant differences existed in the following items between the two groups: feeding intolerance, PN-associated cholestasis, CVC-related bloodstream infection, intestinal fluid reinfusion-related complications, premature closure of fistula and readmission rate within 30 days (all P>0.05). Conclusions:The application of ERAS strategy plus early intestinal fluid reinfusion in neonates with enterostomy is safe and feasible, which can reduce the postoperative durations of PN, CVC and hospital stay and accelerate the recovery.
8.Development and validation of a diagnostic model based on machine learning algorithms for the development of interstitial lung diseases in patients with rheumatoid arthritis
Yancong NIE ; Yanqing JIN ; Meilin YIN ; Xiaoxia WANG ; Lixia QIU
Chinese Journal of Rheumatology 2024;28(3):167-175
Objective:Screening factors that might influence rheumatoid arthritis (RA) complicating interstitial lung diseases (ILD) by constructing and validating a model for early diagnostic.Methods:The study subjects were composed of 712 RA patients in the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University during December 2019 to October 2022. Fifty-two variables such as their demographic data, clinical symptoms, and laboratory indexes were collected. Patients were categorized into RA-only group and RA-ILD group with or without the occurrence of ILD disease. After data preprocessing, subjects were randomly assigned to the modeling and validation groups in a 7:3 ratio.Univariate analysis comparing baseline characteristics of the two groups of patients. Feature selection was performed using LASSO and SVM-RFE regression algorithms.Screening indicators were analyzed by logistic regression and the results were used to develop a nomograms model for the early diagnosis of RA complicating interstitial lung disease; and the modeling group was evaluated for its performance for internal assessment of the model and internal validation using data from the validation group.Results:A total of 712 subjects participated in the study, of which 498 in the modeling group and 214 in the validation group. Univariate analysis showed that the differences between the two groups were statistically significant ( P<0.05) in 18 characteristic indexes, including male, gender, age, smoking history, drinking history, number of swollen joints, number of painful joints, use of prednisone, WBC, ESR, CRP, IL-2, IL-10, IL-17, TNF-α, INF-γ, AFA family, APF, and serum albumin. The LASSO algorithm identified 13 risk variables for RA-ILD, the SVM-RFE algorithm identified 12 variables for RA-ILD, and the intersecting risk variables were male, age, history of alcohol consumption, number of painful joints, prednisone acetate, IL-2, AFA family, TNF-α, serum albumin, and IL-10. The results of multifactorial logistic regression analysis confirmed that the differences between males [ OR(95% CI)=3.61(2.11, 6.18)], gender, age [ OR(95% CI)=1.05(1.03, 1.08)], number of painful joints [ OR(95% CI)=1.03(1.01, 1.06)], IL-2 [ OR(95% CI)=0.91 (0.84, 0.99)], and TNF-α[ OR (95% CI)=1.06 (1.02, 1.10)] were statistically significant ( P<0.05) and were independently influences on ILD complicated by RA. The modeling and validation groups that were used to construct early diagnostic Nomograms had high calibration curve accuracies, and the model had a high diagnostic power, which was mainly demonstrated by the receiver operating characteristic (ROC) area under the curve (AUC) and decision curve analysis(DCA), the model modeling group had an AUC of 0.76 (95% CI=0.71, 0.81), with net benefit rates of 3%~82% and 93%~99%, whereas the model validation group had an AUC of 0.71 (95% CI=0.64, 0.79), with net benefit rates of 5%~11%, 14%~60% and 85%~89%. Conclusion:Male, gender, age, number of painful joints, IL-2, and TNF-α are independent factors for RA complicated with ILD, and the Nomogram model constructed has good performance in early diagnosis of the disease.
9.Effects of Rap1 GTP-activating protein on proliferation,invasion and migration of colon cancer cells
Ying JIN ; Xiaoxia FU ; Ruimin DUAN ; Liyao HAO ; Feng LI
Chinese Journal of Clinical and Experimental Pathology 2024;40(2):144-149,157
Purpose To investigate the corr-elation between Rap1 GAP expression in colon cancer tissues and clinicopatho-logical features and prognosis.Methods Immunohistochemistry was used to detect Rap1 GAP protein expression in 125 cases of colon cancer,and its correlation with clinicopathological features and prognosis was analyzed.Rap1 GAP protein expression in co-lon cancer LOVO,HCT116,SW480 cells and normal colon epi-thelial HCoEPiC cells was detected by Western blot.The expres-sion of Rap1 GAP was down-regulated and up-regulated in LO-VO,HCT116 and SW480 cells by lentivirus transfection,and di-vided into no-load group(sh-NON,LV-NON),sh-Rap1 GAP group(low expression Rap1 GAP)and LV-Rap1 GAP group(overexpression Rap1 GAP)according to different treatments.The transfection efficiency was verified by Western blotting.MTT assay and Transwell assay were used to detect cell proliferation,invasion and migration in each group.Results In 125 colon cancer samples,83 cases(66.4%)had the loss of Rap1 GAP expression,which was higher than that in paracancer control(7.2%,P<0.001).The rate of loss of Rap1 GAP expression was correlated with the degree of tumor differentiation(x2=6.152,P=0.011)and the presence of mucinous adenocarcino-ma(x2=4.908,P=0.028),but not with gender,age,tumor location,tumor stage,or lymph node metastasis(P>0.05).Western blotting results showed that compared with HCoEPiC(0.189±0.081)cells,Rap1 GAP protein expression was in-creased in colon cancer LOVO(0.238±0.008)cells.Rap1 GAP protein expression was decreased in HCT116(0.064± 0.002)and SW480(0.152±0.026)cells(F=159.6,P<0.05).After LOVO cells were transfected with Rap1 GAP low expression lentivirus,the expression level of Rap1 GAP in sh-Rap1 GAP-1 group(0.733±0.071)and sh-Rap1 GAP-2 group(0.559±0.136)and sh-Rap1 GAP-3 group(0.606±0.037)was significantly lower than that in LOVO group(1.880± 0.129)(F=49.57,P<0.05).Compared with sh-NON(1.260±0.109)group,the proliferation ability of sh-Rap1 GAP-2(1.569±0.059)and sh-Rap1 GAP-3(1.548±0.087)cells was significantly increased at 72 h(F=28.36,P<0.05).Its invasion and migration ability were significantly increased(P<0.05).After HCT116 cells transfected with overexpression lentivirus,the expression of Rap1 GAP protein in LV-Rap1 GAP group(1.395±0.137)was relatively higher than that in LV-NON group(0.485±0.097)(P<0.05).The results of MTT assay showed that compared with LV-NON(0.652±0.047)group,the proliferation ability of cells in LV-Rap1 GAP(1.212 ±0.038)group was decreased,and the invasion and migration ability were significantly decreased(P<0.05).The transfection results,proliferation,invasion and migration of SW480 cells were consistent with those of HCT116 cells.Conclusion The loss rate of Rap1 GAP expression is related to the differentiation degree of colon cancer and whether it is accompanied by mucin-ous adenocarcinoma.The up-regulation of Rap1 GAP expression can inhibit the proliferation,invasion and migration of colon cancer cells,providing a theoretical basis for exploring the occur-rence and development of colon cancer.
10.The role of DAAO in arsenic exposure induced learning and memory impairment in offspring mice
Xiaoxia JIN ; Jiaqi SUN ; Huan WANG ; Yan WANG
Chinese Journal of Endemiology 2024;43(6):440-445
Objective:To investigate the role of D-amino acid oxidase (DAAO) in arsenic exposure induced learning memory impairment in offspring mice.Methods:Eighteen Kunming pregnant mice were randomly divided into a non-treatment group (distilled water, n = 6) and an arsenic exposed group [60 mg/L sodium arsenite (NaAsO 2) in drinking water, n = 12] by randomized numerical table method. From the first day of pregnancy until weaning, the mother mice were exposed to arsenic. After weaning, the offspring mice were exposed to arsenic through free drinking water until the end of the experiment. Six weeks after birth, the offspring mice of the arsenic exposed group were divided into a NaAsO 2 group and a NaAsO 2 + DAAO inhibitor 6-chlorobenzo [d] isoxazol-3-ol (CBIO) group according to the group of mother mice. The offspring mice of non-treatment group as the control group. The offspring mice of the control group and NaAsO 2 group were given intraperitoneal injection of 0.5% sodium carboxymethylcellulose, while the NaAsO 2 + CBIO group was given intraperitoneal injection of 60 mg/kg CBIO for two consecutive weeks. At the end of the intervention, the spatial learning and memory abilities of the offspring mice were measured using a Y-maze experiment. After cardiac perfusion, brain tissue was taken from the offspring mice and the hippocampus was isolated. Hematoxylin-eosin (HE) staining was used to observe the morphology of the hippocampal neurons in the offspring mice. D-serine content was determined by ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS). The mRNA levels of synaptophysin (SYP), synaptosomal-associated protein 25 (SNAP25), postsynaptic density 95 (PSD95), DAAO, and N-methyl-D-aspartate receptor (NMDAR) subunits NR1, NR2A, NR2B were measured by real-time fluorescence quantitative PCR. Results:There was a statistically significant difference in the offspring mice alternating response rate of the Y-maze experiment among the control, NaAsO 2, and NaAsO 2 + CBIO groups [ (58.06 ± 3.78) %, (48.61 ± 5.75)%, (56.25 ± 6.76)%, F = 4.87, P = 0.023], and the NaAsO 2 group was significantly lower than the control and NaAsO 2 + CBIO groups ( P < 0.05). The HE staining results showed that the control group had a higher number of neuronal cells in the CA1 and CA3 regions of the hippocampal tissue, and they were in good condition. The number of neuronal cells in the NaAsO 2 group decreased, with irregular morphology and unclear cell contours. The NaAsO 2 + CBIO group had a higher number of neuronal cells, improved cell morphology and contour, and reduced tissue damage. There were statistically significant differences in D-serine content and mRNA levels of SYP, SNAP25, PSD95, DAAO, NR1, NR2A, and NR2B in the hippocampus of the offspring mice from the control, NaAsO 2, and NaAsO 2 + CBIO groups ( F = 5.41, 4.41, 10.16, 7.60, 6.98, 5.63, 6.53, 4.33, P = 0.017, 0.031, 0.002, 0.005, 0.007, 0.015, 0.009, 0.033). Among them, the D-serine content and mRNA levels of SYP, SNAP25, PSD95, NR1, and NR2B in the hippocampus of the NaAsO 2 group were significantly lower than those in the control group and NaAsO 2 + CBIO group, the mRNA level of NR2A was significantly lower than that in the control group, and the mRNA level of DAAO was significantly higher than that in the control and NaAsO 2 + CBIO groups ( P < 0.05). Conclusions:Arsenic exposure can induce the learning and memory impairment in offspring mice, reduce D-serine content in the hippocampus, as well as the transcription level of NMDAR subunits and synapse-associated proteins, up-regulate the transcription levels of DAAO; and inhibit DAAO, leading to increased D-serine content, the transcription levels of NMDAR subunits and synapse-associated proteins, improving arsenic exposure induced learning and memory impairment in the offspring mice.

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