Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

Background Polycyclic aromatic hydrocarbons represented by benzo[a]pyrene are among the most significant occupational and environmental pollutants. Exposure to benzo[a]pyrene during pregnancy can cause delayed intellectual development in offspring, and the mechanism may be related to the expression of protocadherin (Pcdh), a key molecule for learning and memory. Objective To explore the possible role of Pcdh in impaired learning and memory function of pups caused by benzo[a]pyrene exposure during pregnancy by establishing an animal model of cognitive impairment in pups caused by benzo[a]pyrene exposure during pregnancy, and detecting the expression of Pcdh and its transcription-related factors in the hippocampal tissues of pups at different developmental stages. Methods Sixty female and male SPF-grade rats were caged in a 1:1 ratio overnight, and the successfully mated female mice were randomly divided into blank control, 0 mg·kg⁻¹, 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups, with 6 mice in each group. They were intraperitoneally injected with benzo[a]pyrene from the 17th to the 19th day of pregnancy to establish an exposure model. Learning and memory functions of the offspring were tested through Morris water maze on the 45th day after the birth (PND) of the pups. On the PND45 and PND75 of the pups, hippocampal tissues of 6 pups (per group) were collected respectively. The expression levels of PcdhαC1 and wings apart-like homolog (WAPL) genes and proteins were detected by fluorescence quantitative polymerase chain reaction (PCR) and Western blotting. Results The results of Morris water maze showed that there was no interaction between the escape latency time of the pups and the dose groups of 0 mg·kg⁻¹, 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ (F _{time × group}=0.515, P>0.05). The escape latency of pups decreased with increase of training time (F _time=24.678, P<0.001, F _group=12.803, P<0.001). The PCR results showed that at PND45, compared with the blank group, the relative expression levels of PcdhαC1 mRNA in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the relative expression levels of WAPL mRNA increased (P<0.05). At PND75, compared with the blank group, the relative expression levels of PcdhαC1 mRNA in the 20 mg·kg⁻¹ and 40 mg·kg⁻¹ groups decreased (P<0.05), and the relative expression levels of WAPL mRNA increased (P<0.05). The Western blotting results showed that at PND45, compared with the blank group, the expression levels of PcdhαC1 protein in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the expression levels of WAPL protein increased (P<0.05). At PND75, compared with the blank group, the expression levels of PcdhαC1 protein in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the expression levels of WAPL protein increased (P<0.05). Conclusion Exposure to benzo[a]pyrene during pregnancy can cause impairment in the learning and memory abilities of PND45 offspring and may alter the expression of PcdhαC1 and WAPL genes and proteins.

Objective To investigate the effects and mechanisms of five-element music on the social behavior of the children of mothers with fear stress during pregnancy and provide a basis for the early prevention and treatment of clinical fetogenic affective disorders.Methods Forty-five pregnant mice were randomly divided into three groups:a control group,model group,and five-element music group.The model and five-element music group models were established using the bystander electric shock method.Additionally,the five-element music group was exposed to Palace Tune five-element music daily from 17:00 to 19:00 during pregnancy.On the 19th day of pregnancy,ELISA was employed to assess the levels of adrenocorticotropin(ACTH)and cortisol(CORT)in the serum of pregnant mice in each group for modeling evaluation.The offspring were subsequently grouped with their mother and underwent an 8-week-old three-box social experiment to observe their social behavior.We used the immunofluorescence double-labeling method to detect glutamatergic neuron activity in the medial prefrontal cortex(mPFC)of the offspring.High-performance liquid chromatography was employed to measure the total glutamate(Glu)content in the mPFC,while Gorky staining was used to observe changes in the dendritic spines of mPFC neurons in the offspring.Results Compared to those in the blank group,pregnant mice in the model group exhibited a significant increase in the levels of ACTH and CORT in their serum,and there was a significant decrease in the social interaction time and social novelty preference index of their offspring.There was also a significant decrease in glutamate neuron activity,glutamate content,and neuronal dendritic spine density.In contrast,compared with those in the model group,pregnant mice in the five-element music group demonstrated a reduction in the levels of ACTH and CORT in the serum,and there were improvements in the social behavior,glutamate neuron activity,glutamate content,and condition of neuronal dendritic spines in the offspring.Conclusions Intervention with five-element music effectively ameliorated the offspring's social behavior disorder result ing from prenatal fear stress;the mechanism was potentially linked to enhanced glutamate neuron activity in the mPFC region.

Objective To establishment a process of monitoring waste resin clearance in nuclear power plants, and to meet clearance requirements and simplify the monitoring work. Methods In accordance with the requirements specified in current laws, regulations, and standards in China, as well as the practice of slightly polluted waste resins generated during the operation of nuclear power plants, in-depth discussion was conducted on sampling methods, sample uniformity and representativeness tests, radiation monitoring contents and methods, and simplified monitoring processes, in order to accurately monitor the radionuclide activity of waste resins to be cleared. Results A process was established to monitor waste resin clearance in nuclear power plants. A total of 55 barrels of waste resins were cleared and the radiation levels met the requirements. Conclusion An effective clearance process can facilitate the sampling of representative resins, improve the accuracy of monitoring data, differentiate radioactive waste from cleared waste, and simplify the monitoring process. Our results provide a basis and reference for future waste resin clearance.

Objective: To examine the causal relationship between inflammatory factors and breast cancer using two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and treatment of breast cancer. Methods: Data of 91 inflammatory cytokines (n=14 824) and 5 subtypes of breast cancer (n=247 173) were collected from genome-wide association studies (GWAS). Single nucleotide polymorphism (SNP) associated with 91 inflammatory factors were selected as instrumental variables. MR analyses were performed using the inverse-variance weighted (IVW) method with inflammatory factors as exposure factors and breast cancer as outcome variables. The risk of type I error and the effect of multiple testing were reduced using the FDR correction method. The stability and reliability of the results were verified using Steiger test of directionality, MR-Egger regression, MR-PRESSO test and leave-one out method. Results: Twenty-three inflammatory factors, including β nerve growth factor, interleukin-5, cystatin D and C-X-C chemokine ligand 1 were statistically associated with breast cancer (all P<0.05). After FDR adjustment, only evaluated abundance of oncostatin-M was found to be statistically associated with an increased risk of Basal-like (triple-negative) breast cancer (OR=1.186, 95%CI: 1.081-1.302, P=0.001, q=0.029), and the other 22 inflammatory factors had a high risk of type I error (all q>0.1). The sensitivity analysis indicated that the results were robust. No instrumental variables were found to have a significant impact on the results, which could exclude the influence of heterogeneity, horizontal pleiotropy, and reverse causality on the outcome. Conclusion The increased abundance of oncostatin-M may increase the risk of Basal-like (triple-negative) breast cancer.

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg^-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg^-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Objective:To explore the clinical value of peripheral blood lymphocyte subsets in the differential diagnosis of BK virus nephropathy (BKVN) in renal transplantation recipients.Methods:From 2014 to 2018, a total of 172 renal transplant recipients were recruited. Their peripheral blood lymphocyte subsets were detected. According to the pathological puncture results of transplanted kidney, they were divided into acute rejection group (AR, n=68), BKVN group ( n=73) and stable graft function group (STA, n=31). The proportion and absolute number of peripheral blood lymphocyte subsets in each group were measured by flow cytometry and the proportion and absolute count of peripheral blood lymphocyte subsets in each group compared. Results:The proportion and absolute number of CD19 + B cells were markedly lower in BKVN group than those in AR group ( P=0.005, 0.003; 8.5% vs 13.2%, 0.094×10 9/L vs 0.202×10 9/L) and STA group ( P=0.005, 0.003; 8.5% vs 14.8%, 0.094×10 9/L vs 0.198×10 9/L); the proportion of CD3 + CD8 + T cells was significantly higher in BKVN group than that in AR group ( P=0.013; 36.9% vs 31.2%). In addition, no obvious difference existed in the proportion and absolute number of lymphocytes, CD3 + T, CD3 + CD4 + T and CD16 + CD56 + natural killer (NK) among three groups ( P>0.05). No obvious difference existed in the proportion of CD3 + CD4 + / CD3 + CD8 + T cells among three groups ( P>0.05). Conclusions:No difference exists in T cell-related lymphocyte subsets between BKVN and acute rejection recipients. However, the number and proportion of CD19 + B cells decrease markedly in BKVN.

Objective: To explore the clinical and prognostic features of lipoprotein glomerulopathy (LPG) in renal allografts. Methods: Retrospective analysis was performed for two case of LPG in renal allografts. The onset time was 6 and 9 years after living transplantation respectively. Initial symptoms included proteinuria and hypoproteinemia. Color Doppler ultrasound showed an enlarged graft size and greater parenchymal echogenicity. One patient had hyperlipemia and elevated apolipoprotein E (ApoE). Methylprednisolone pulse was offered with an early control of hyperlipidaemia and proteinuria by fenofibrate and angiotensin-converting enzyme inhibitors (ACEIs). Yet it had no effect on graft function. The definite diagnosis was made by graft biopsy. Pathological examination indicated non-homogeneous lipid deposition in glomerular capillary, glomerular sclerosis, mesangial hypercellularity and tubular atrophy. Results: During a follow-up period of 8 and 10 years post-transplantation, two cases eventually lost their grafts within 2 and 1 year after biopsy respectively. With long-term dietary control and drug therapy, regular dialysis continued and both awaited a second transplantation. Conclusions LPG is generally steroid-resistant and refractory in renal allografts. And routine biopsy is recommended for patients with a high risk of occurrence. Early controls of hyperlipemia and hypoproteinemia and other risk factors should be also properly managed.

Objective To use the "three-dimensional quality structure" model as a theoretical basis, based on multiple evidence-based evidence, to construct ICU nursing sensitivity quality indicators, and to provide reference for the evaluation and monitoring of ICU department nursing safety quality. Methods Evidence-based and Delphi methods were used to complete 3 rounds of inquiry among 27 experts to obtain consensus opinions of experts and to determine nursing quality indicators. Results Of the 30 articles included, 17 wereⅢA, 10 wereⅣA, 2 wereⅤA, and 1 wasⅤB. According to the"three-dimensional structure theory"model, the included indicators were sorted out and a total of 12 items were obtained. The effective recovery rate of 3 rounds of questionnaires was 96.6％, 100.0％, and 96.4％. The authoritative coefficients were 0.899, 0.895, and 0.909, and the coordination coefficients of the first, second, and third indexes were 0.340, 0.379, and 0.403, respectively,with significance (P<0.01). The final ICU nursing sensitivity quality indicator consists of 3 first-level indicators, 15 second-level indicators and 69 third-level indicators. The selection of indicators at all levels gradually converges. Conclusions The established ICU nursing sensitivity quality index accords with the principle of scientificity and practicality, and can be used for ICU department nursing quality assessment.

Objective To investigate the effectiveness and safety of carbapenem antimicrobial management programs (ASP). Methods 671 patients who were discharged from the emergency department of the hospital from January 2017 to April 2018 were enrolled. These patients were subject to before-and-after self-control studies, using such intervention measures as MDT proactive management-feedback-training. January-September of 2017 was set as the pre-intervention stage, and September 2017-April 2018 as the post-intervention stage. The two stages were compared in such indicators as the monthly antibacterial use, quality of care and hospital acquired infection. Results Thanks to the ASP measure against antibiotics like carbapenems, the use rate of carbapenems at the emergency department ward fell from 36.7% to 18.6% , the defined drug doses (DDDs) of carbapenems fell from 211.92 to 82.22, and the antibiotics use density (AUD) of carbapenems fell from 29. 18 DDDs/100 day/patient to 11. 56. The pathogen detected rate increased significantly (0.61 ± 0.08 versus 0.78 ± 0.16), with a difference of statistical significance (P=0.020). On the other hand, the mean days of stay, average cost per hospitalization, proportion of antibiotics use, incidence of hospital acquired infections, and the infection/colonization rate of carbapenem-resistant organisms ( CROs ) present no significant changes. There was a moderate positive correlation between carbapenem DDDs and mean days of stay ( P=0.034), and also a moderate positive correlation between hospital acquired infection incidence and CROs infection/colonization rate ( r = 0.545, P = 0.029 ). Conclusions The carbapenem ASP at the hospital proves safe and effective. CROs infection/colonization may be the cause of hospital acquired infection. Prevention and control against multi-drug resistant bacteria on the basis of ASP may add to the effect of ASP.