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.

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.

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.

This paper aims to review treatment delay in first-episode schizophrenia,depression,and bipolar disorder,and to compare related factors of treatment delay in the three first-episode mental disorders.It is found that increased patient responsibility,stigma,lack of disease-related knowledge,lack of access to resources,and insuffi-cient medical support lead to delay treatment,and making patients to have longer course,heavier symptoms,and lower social functions.

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.

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.

Objective To explore the correlation between serum fibroblast growth factor-23 (FGF23) concentration and heart failure and all-cause death in patients with end-stage renal disease (ESRD).Methods The prospective cohort study design was used in the present study.The ESRD patients who were admitted to the department of ne-phropathy in the Hospital and without heart failure symptoms were recruited in this study.The data of patients was collected through baseline questionnaires, physical examinations, echocardiography, and laboratory examinations.The serum FGF23 levels were measured by enzyme-linked immunosorbent assay (ELISA) .The follow-up time was 2 years.The onset of heart failure (ACC/AHA stage C-D) and all-cause death were composite endpoint events.The Cox proportional risk model was used to explore the risk factors of outcome events.Through subgroup analyses and interaction analyses, further exploration was conducted to determine whether there was heterogeneity in the as-sociation between FGF23 and outcome events in different subgroups.Results Ultimately,107 ESRD patients were included in this study, with an average age of (52.00 ± 12.51) years.There were 39 males (36.45％), and the median follow-up time was 23 months (21, 25 months).There were 32 (29.9％) outcome events, of which 22 (20.6％) onset of heart failure and 10 (9.3％) all-cause of deaths.The results of this study showed that the con-centration of FGF23 in the outcome event group was significantly higher than that in the non-event group [ (4.40 ± 1.16) pmol/ml vs (3.85 ± 0.82) pmol/ml,P<0.05].The Cox proportional risk model showed that the elevated FGF23 was associated with increased risk of the composite endpoint events in ESRD patients (HR=1.730 , 95％CI:1.164-2.570 , P=0.007) .Subgroup analyses showed that there was an interactive effect between FGF23 levels and gender on the risk of cardiovascular outcome events.Especially in male ESRD patients, the increased FGF23 level was correlated with a higher risk of cardiovascular events (P-interaction <0.05).Conclusion Elevated serum FGF23 is an independent risk factor for the onset of heart failure and all-cause of mortality in ESRD patients, especially in male patients.

Objective:To explore the value of multimodal ultrasound parameters combined with peripheral blood lymphocyte-monocyte ratio (LMR) in predicting recurrence and metastasis after radical breast cancer surgery.Methods:A total of 139 patients with breast cancer admitted to Northwest Women’s and Children’s Hospital from Jan. 2021 to Jan. 2022 were studied. The patients underwent postoperative multimodal ultrasonography and peripheral blood lymphocyte and monocyte examination. Patients were followed up for 2 years after surgery to evaluate postoperative recurrence and metastasis, and analyze the value of multimodal ultrasound parameters combined with LMR in predicting recurrence and metastasis of patients.Results:Among 139 patients, 32 recurrences and metastases occurred during 2-year follow-up; The peak systolic velocity (PSV), resistance index (RI), maximum lesion diameter, elasticity score, area under the curve (AUC) and peak intensity (PI) in patients with recurrent metastasis were higher than those without recurrent metastasis ( t=7.37, 4.75, 4.75, 5.46, 4.24, 5.22, P<0.05), and the LNR in patients with recurrent metastasis was lower. Pearson correlation analysis showed that PSV, RI, maximum lesion diameter, elasticity score, AUC, PI were negatively correlated with LMR ( r=-0.418, -0.502, -0.633, -0.526, -0.448, -0.482). P<0.05) ; The ROC curve showed that the AUC of PSV, RI, maximum lesion diameter, elasticity score, AUC, PI and LMR for predicting recurrence and metastasis were 0.852, 0.784, 0.791, 0.789, 0.615, 0.725 and 0.728, respectively, and the combined AUC value of each index was 0.992. Conclusions:The use of multimodal ultrasound parameters combined with LMR can improve the prediction value of recurrence and metastasis after radical breast cancer surgery.

Objective To evaluate the technical feasibility and safety of upper arm vein approach in the implantation of totally implantable venous access port(TIVAP)under the guidance of ultrasound combined with DSA.Methods The clinical data of 1 546 patients with malignant tumors,who received TIVAP implantation via upper arm vein access under the guidance of ultrasound combined with DSA at the Affiliated Renji Hospital,School of Medicine of Shanghai Jiao Tong University of China between January 2020 and January 2022,were retrospectively analyzed.The implantation success rate,single-puncturing success rate,operation time,and complications were compared between the PICC catheterization room and the DSA operating room.Results The technical success rate in the 1546 patients was 100％,with a single-puncturing success rate of 99.48％.In 766 patients the TIVAP implantation was performed in the PICC catheterization room(PICC group),and in 780 patients the TIVAP implantation was carried out in the DSA operating room(DSA group).The mean operation time in the DSA group was(20.1±1.3)min,which was obviously shorter than(25.4±1.9)min in the PICC group,and the incidence of primary catheter misplacement in the DSA group was 0％,which was remarkably lower than 0.78％in the PICC group(P＜0.05).No statistically significant differences in the incidences of complications,including infection,thrombosis,upper limb movement disorder,catheter occlusion,exposure of infusion port body,and overturn of infusion port body,existed between the two groups(P＞0.05).Conclusion Ultrasound-guided TIVAP via upper arm vein approach is a safe and effective infusion route for patients with malignancy receiving chemotherapy.The combination use of ultrasound guidance and intraoperative DSA guidance can reduce the operation time as well as the incidence of operation-related complications.

Humans ; Asthma/drug therapy* ; Biological Therapy