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.

Objective : To establish a method for measuring major organic acids in the tricarboxylic acid cycle using a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) system, and to investigate the changes in six tricarboxylic acid cycle organic acids(fumaric acid, malic acid, succinic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid) in the serum, liver, and placenta of mice exposed to di(2-ethylhexyl) phthalate(DEHP) during pregnancy. Methods : The serum, liver and placental samples from pregnant mice were processed and eluted through a Waters ACQUITY UPLC BEH Amide Column(130 Å, 1.7 μm, 2.1 mm × 150 mm) using a gradient elution program. Mobile phase A comprised an aqueous solution of 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, while mobile phase B consisted of a 90% acetonitrile aqueous solution containing 10 mmol/L ammonium acetate and 5 μmol/L methanephosphonic acid, with a flow rate maintained at 0.35 ml/min. The mass spectrometry detection system utilized an electrospray ionization technique with negative ion mode for multiple reaction monitoring. Results : The correlation coefficients of the standard curves for the six tricarboxylic acid cycle organic acid metabolites were all above 0.996 within the quantitative range. The method's accuracy ranged from 97.14% to 108.26%, with inter-day and intra-day precision relative standard deviation between 1.35% and 6.73%. The matrix effect was between 93.29% and 107.47%, and the extraction recovery rate ranged from 94.82% to 112.57%. Analysis of six tricarboxylic acid cycle organic acids in the liver, serum, and placenta of DEHP-exposed mice during pregnancy showed significant reductions in fumaric acid, malic acid, α-ketoglutaric acid, cis-aconitic acid, and citric acid compared to the control group(P<0.05). Conclusion The HPLC-MS/MS method established in this study for detecting six tricarboxylic acid cycle organic acids in the serum, liver, and placenta of DEHP-exposed pregnant mice is stable, highly sensitive and selective. Prenatal DEHP exposure induced alterations in the levels of tricarboxylic acid(TCA) cycle organic acid metabolites in the liver, serum, and placenta of mice, suggesting that DEHP exposure during pregnancy may interfere with mitochondrial TCA cycle processes. These findings indicate potential value in the diagnosis and treatment of diseases associated with prenatal DEHP exposure.

Objective:To explore the application and diagnostic value of low-dose scan technique of chest computed tomography(CT)combined with three dimensional(3D)reconstruction for ribs in chest trauma.Methods:A total of 118 patients with highly suspected rib fracture who admitted to the 904th Hospital of People's Liberation Army Joint Service Support Force were selected,and all cases underwent low-dose scan technique of chest CT combined with 3D reconstruction for ribs.The image qualities of chest CT scans with different low-doses combined with 3D reconstruction for ribs were analyzed,and the diagnostic accuracies among low dose scan technique of chest CT,3D reconstruction for ribs and the combination of them for chest trauma were compared.Results:Both the sharpness and clarity of the edges of the bronchi,blood vessels,lung parenchyma,interlobular septum,mediastinum and ribs were poorer,and the artifacts of soft tissue were more and the noise were more when the tube current of CT scan was 50 Ma.Both the sharpness and clarity of the edges of the bronchi,blood vessels,lung parenchyma,interlobular septum,mediastinum and ribs were general,and a part of soft tissues existed artifacts and the noise amounts were less when the tube current of CT scan was 70 Ma,which did not affect the diagnosis.The radiation dose as 50 mA was significantly higher than that as 70 mA,with a statistically significant difference(t=10.969,P<0.05).In 118 patients with chest trauma,the examination of low-dose scan technique of chest CT combined with 3D reconstruction for ribs indicated that there were 112 cases of rib fractures and 7 cases of costal cartilage fractures.In the examined 388 fractures of rib and costal cartilage,355 fractures(91.49%)were rib fractures and 33 fractures(8.51%)were costal cartilage fractures.In 118 patients with chest trauma,76 cases(64.41%)complicated with pulmonary contusions and lacerations,and 41 cases(35.75%)complicated with pleural effusion,and 10 cases(8.47%)complicated with thoracic vertebral fractures,and 6 cases(5.08%)complicated with splenic contusions and lacerations,and 5 cases(4.24%)complicated with mediastinal and subcutaneous emphysemas.The most direct imaging sign of rib fracture was visible and transparent low-density shadow.Chest CT scan can generally better display dislocation of the fractured end.The 3D reconstruction image showed a visibly line-like shadow on one side of rib if only one side of ribs fractured and the other side was intact.A total of 395 rib and costal cartilage fractures were confirmed by 3D reconstruction,which included 363 rib fractures(91.90%)and 32 costal cartilage fractures(8.10%).A total of 410 rib and costal cartilage fractures were confirmed by low-dose scan technique of chest CT combined with 3D reconstruction for ribs,which included 375 rib fractures(91.46%)and 35 costal cartilage fractures(8.54%).In the comparison of 418 rib injuries that were confirmed during surgery,the accuracy of low-dose scan technique of chest CT was 92.82%(388/418)in diagnosing rib and costal cartilage fractures,and the accuracy of 3D reconstruction for ribs was 94.50%(395/418)in diagnosing that,and the accuracy of low-dose scan technique of chest CT combined with 3D reconstruction for ribs was 95.69%(410/418)in diagnosing that.There was a significant difference in accuracy among the three types of examinations(x2=13.062,P<0.05).Conclusion:Low dose scan technique of chest CT combines with 3D reconstruction for ribs can be used in the diagnosis of chest trauma,which has higher accuracy and can provide reliable imaging information for clinical diagnosis and treatment.

Objective To explore the differences of gene expression of peripheral blood mononuclear cell (PBMC) between the anti-cyclic citrullinated peptide antibody (ACCPA) positive and ACCPA negative patients with rheumatoid arthritis (RA) by microarray analysis.Methods Total RNA was extracted from PBMC of 5 ACCPA positive and ACCPA negative patients with RA,and age-and sex-matched control subjects respectively.Ⅲumina oligonucleotide microarray was used to characterize 47231gene expression profile for each sample.Results Among the target genes,88 differentially expressed genes were identified in RA patients.Fifty-one up-regulated genes and 37 down-regulated genes were found in RA patients compared to those in control subjects (fold change＞1.5).The differential expression of genes were associated with apoptosis,cytokine,signal identification protein,chemotaxis factor etc.There were 20 differential expression genes between the ACCPA positive and ACCPA negative patients with RA,9 up-regulated genes and 11 downregulated genes were found.The differential expression genes were associated with protein biding,,translation control,signal identification protein,cell cycle,metabolism etc.Conclusion There are differential gene expression between the ACCPA positive and ACCPA negative patients with RA.Genes screened from the target such as IFI,KIR,CHI3L1 can provi-de important information for further study and treatment of RA.