The purpose of risk assessment is to evaluate the permissible exposure level under specific risk factors.To extrapolate the human acceptable daily intake (ADI) and/or reference dose (RfD), the traditional method uses the no-observed-adverse-effect level ( NOAEL ) to quantify toxicity after being divided by uncertainty factor.There are many limitations with NOAEL method in safety evaluation,for it relies too much on experimental design.Benchmark dose ( BMD) approach is a more reliable method with many advantages.BMD approach and its analysis software, the advantages of BMD over NOAEL, the application and methodological perfection in risk assessment of long-team exposure toxicity are presented in this review.

Chronic kidney disease (CKD) is a serious chronic disease with high incidence, poor prognosis, and a variety of complications. Indoxyl-sulfate (IS) and p-cresol sulfate (PCS) are two typical gut-derived uremic toxins, which are produced by the co-metabolism of intestinal microbes and the host. With the progression of CKD, gut-derived uremic toxins such as IS and PCS accumulate in patients with CKD and thereafter accelerate the progression of CKD. Gut microbiota is closely related with CKD, and targeting gut microbiota to regulate gut-derived uremic toxins synthesis and metabolic pathways may be a promising strategy to delay the progression of CKD. In this paper, the relationship between gut microbiota, gut-derived uremic toxins, and CKD was analyzed, and the strategy to delay the progression of CKD by targeting gut microbiota and uremic toxins metabolism pathway was proposed.

Hepatic encephalopathy is a common metabolic neuropsychiatric syndrome in the development of end-stage liver disease. Since the concept of intestinal-liver-brain axis was proposed, the relationship between the pathogenesis of hepatic encephalopathy and the gut microbiota has been a hot research topic. In recent years, studies have confirmed that gut microbiota is involved in and affects various pathological processes of hepatic encephalopathy. This article combines the latest research progress at home and abroad to elaborate on the research status of regulating gut microbiota and thus interfering with the pathological process of hepatic encephalopathy, hoping to provide new ideas and methods for the intervention of hepatic encephalopathy based on the regulation of gut microbiota.

Objective To investigate the clinical significance of generalized epilepsy with febrile seizures plus(GEFS+ ). Methods The data of one family with GEFS+ were retrospectively analyzed by studying clinical manifestations, physical examinations, electroencephalogram(EEG), 24 hours dynamic EEG monitoring, et al. Some of the patients were examined by CT. Results Ⅳ 12, her chief complaints when admitted to hospital were frequent spasm for 3 days. She began to appear febrile seizures (FS) from 8 months after birth, and frequent generalized tonic - clonic FS appeared during that time. There were 36 people in 5 generations of the family including 14 patients (8 males and 6 females) ,aged from 4 years and 5 months to 82 years. FS presented in 8 cases (Ⅱ 2, Ⅲ1, Ⅲ4, Ⅲ6, Ⅳ1, Ⅳ11, Ⅳ17, Ⅴ2),febrile seizures plus(FS +) in 4 cases ( Ⅳ2, Ⅳ12, Ⅳ13, Ⅳ14), ES + and absence seizures in 1 case ( Ⅴ1 ), uncertain type in 1 case (Ⅰ2). The results of EEG indicated that 12 cases were normal and 4 cases with FS+ and 1 case with absence seizures had epileptic discharges. Apart form Ⅳ13, Ⅳ14 who were treated with magnesium valproate, the dosage for the other patients decreased, or medicine terminated or without medicine, and all the patients had no recurrence of seizures. The intelligence, movement development and neurological examinations of the family were all normal. Head CT scan of 3 cases were normal. Conclusions GEFS+ is autosomal dominant inheritance disease with conspicuous genetic heterogeneity and phenotypic heterogeneity. The apprehension of GEFS+ plays an important role in diagnosis and differential diagnosis of epilepsy in childhood.

Objective To investigate the clinical and neuroimage characteristics of reversible posterior leukoencephalopathy syndrome (RPLS) in Chinese elderly patients. Methods The characteristic clinical presentation and neuroimaging of 5 elderly patients with RPLS were retrospectively analyzed. Results There were one male and four females in this study, with the average age of (63.0±2.4) years, all combined with hypertension. The most common clinical presentations were abnormality of visual perception (5 cases), headache (4 cases), epileptic seizure (4 cases), disturbance of consciousness (3 cases), pathological reflex (2 cases) and hemiplegia (2 cases). CT scan showed 4 cases with low density lesions. MR1 scan showed 5 cases with occipital lobe lesions, 2 with parietal lobe lesions and 1 with temporal lobe lesions. Re-examination of CT scans showed that 4 survived patients became normal at mean (48.8±29.2) days after discharging from hospital. Conclusions The etiologies of RPLS are diverse. The vasogenic theory is supported by neuroimage of RPLS. Neuroimage may be very important for the diagnosis of RPLS. Diffusion-weighted imaging and apparent diffusion coefficient map may be helpful for differential diagnosis between RPLS and cerebral infarct.

Objective To investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of sarcoidosis.Methods Twenty-two cases of clinically suspected sarcoidosis underwent bronchoscopy and ultrasound bronchoscopy examination,including endobronchial biopsy (EBB),transbronchial lung biopsy (TBLB),and EBUS-TBNA.The biopsy samples of EBB,TBLB,and EBUS-TBNA were paraffin-embedded for hematoxylin eosin (HE) staining and acid-fast staining,respectively.Differences in the diagnosis of sarcoidosis were compared among EBB,TBLB,and EBUS-TBNA.The diagnostic performance of EBUS-TBNA was evaluated.Interventional pulmonology diagnostic strategy of sarcoidosis was analyzed.Results Among all the 22 patients with suspected sarcoidosis,20 cases were diagnosed as sarcoidosis,1 case was small cell lung cancer,and 1 case was lymphoma.The number of patients who were diagnosed by EBB,TBLB,and EBUS-TBNA was 6 cases,9 cases,and 16 cases,respectively;and their diagnostic yield was 30.0％,45.0％,and 80.0％,respectively.The diagnostic yield of EBUS-TBNA was significantly better than the other two (P =0.005).Combined EBB and EBUS-TBNA,the diagnostic yield was 85.0％.Combined TBLB and EBUS-TBNA,the diagnostic yield was 90.0％.Combined those three,the diagnostic yield was 95.0％.EBUS-TBNA diagnostic yield was affected by the location and size of lymph nodes.The diagnostic yield of subcarinal lymph nodes and paratracheal lymph nodes by EBUS-TBNA was significantly better than that of Hilar lymph nodes (x2 =4.29,P ＜0.05),EBUS-TBNA showed better diagnostic yield for the lymph nodes whose diameter was greater than 2cm (x2 =4.067,P ＜ 0.05).EBUS-TBNA had fewer complications.Most patients only had a little bleeding in puncture site.Conclusions EBUS-TBNA contributed to diagnose sarcoidosis,while TBLB and EBB had a complementary value in the diagnosis of sarcoidosis by EBUS-TBNA.

ObjectiveTo explore the changes in gene expression in tissues of patients with gastric carcinoma by cDNA microarray.MethodsA 44,000 gene cDNA microarray (Affymetfix) was used to examine gene expression in the tissues of patients with gastric carcinoma.The Sirt1 genes were identified and subjected to realtime PCR analysis.Results The expression of Sirt1 in tissues of gastric carcinoma [(0.318 ±0.032) ～ (0.169 ±0.013 ) time] was extremely lower than in tissues of para- gastric carcinoma ( 1 time).The results of Real-time PCR were consistent with those of genechip analysis.ConclusionsThe expression of Sirt1 was obviously different between tissues of gastric carcinoma and para - gastric carcinoma.Sirt1 may be associated with carcinogenesis of HCC.

Objective To identify the miR-217 targeted gene ANLN by experiment.Methods Bioinformatic algorithms were used to predict the potential targets of miR-217.Then,ANLN binding with miR217 and mutant ANLN (mutANLN) sequence were designed and synthesized,and their amplified fragments were inserted into plasmid psiCHECK-2,and recombinant plasmid psiCHECK-2-ANLN and psiCHECK-2-mutANLN were reconstructed.The two recombinant plasmids were co-transfected into pancreatic cancer cell line PANC1 with miR-217,miR-217 inhibitor,NC,NC inhibitor by liposome,respectively.Dual luciferase reporter system was used to determine the luciferase activity,and Western blot was used to measure the expression of ANLN protein.Results The luciferase activities of psiCHECK-2-ANLN,psiCHECK-2-ANLN +miR-217,psiCHECK-2ANLN + miR-217 inhibitor,psiCHECK-2ANLN + NC,psiCHECK-2-ANLN + NC inhibitor were 2.221 ± 0.188,0.769 ± 0.061,3.764 ± 0.371,2.265 ± 0.201,2.242 ± 0.018,and the difference among these groups was statistically significant (F =77.405,P ＜0.001),but the difference among psiCHECK-2ANLN group,psiCHECK-2-ANLN + NC group and psiCHECK-2-ANLN + NC inhibitor group was not statistically significant.However,luciferase activities of psiCHECK-2-ANLN + miR-217 group were significantly decreased when compared with other 3 groups,and luciferase activity of psiCHECK-2-ANLN +miR-217 inhibitor group were significantly increased when compared with other 4 groups (all P ＜0.001).Luciferase activities of groups transfected with psiCHECK-2-mutANLN was not significantly different (P =0.053).The expression of ANLN protein in PANC1 with psiCHECK-2-ANLN + miR-217 co-transfection was significantly down-regulated when compared with that with psiCHECK-2-ANLN transfection alone.Conclusions ANLN is one of the direct target genes of miR-217 in PANC1 cells.

The purpose of this study was to synthesize and evaluate the necrosis target of MRI contrast agent based on rhein.The novel ligand 10-{ [6-(1,8-dihydroxyanthraquinone-3-carboxamido) hexyl] amino} acetyl-1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid (DO3A-rhein) was synthesized by two-step acylation and two-step deprotection.The paramagnetic contrast agent gadolinium 10-{ [6-(1,8-dihydroxyanthraquinone-3-carboxamido) hexyl] amino} acetyl-1,4,7,10-tetraazacyclododecan-1,4,7-triacetate (Gd-DO3A-rhein) was obtained by coordination of Gd3+ with the synthesized ligand.Its necrosis affinity was evaluated by liver infarction and muscular necrosis on rat models.The MRI was performed before administration of Gd-DO3A-rhein and during 0 h to 12 h after administration of Gd-DO3A-rhein (0.1 mmol/kg),respectively,and Gd-DOTA was used as control.After MRI scanning,rats were sacrificed and necrotic tissues were stained using triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE).MRI images of liver infarction and muscular necrosis on rat models showed significantly enhanced signal intensity compared with normal tissues.The contrast ratios of necrotic liver/normal liver were 1.61 ±0.14 and 2.36 ±0.20 at 3 h and 12 h postinjection of Gd-DO3A-rhein (0.1 mmol/kg) respectively,demonstrating a significant difference compared with pre-administration of Gd-DO3A-rhein (1.16 ±0.10;P ＜ 0.05).The same results were obtained from necrotic muscles.These findings suggested that Gd-DO3A-rhein possessed the necrosis target and imaging capability of necrotic tissues.

Objective To observe the effect of lentiviral vector-mediated basic fibroblast growth factor (bFGF) gene transfection on the biological characteristics of rabbit bone marrow stromal cells(BMSCs)under in vitro culture conditions. Methods BMSCs were obtained by density gradient centrifugation and adherence screening. The bFGF gene was transfected into BMSCs by lentiviral vector and divided into bFGF transfection group,empty virus group and untransfected group according to the transfection conditions.After transfection,the morphology,expressions of bFGF mRNA and protein, cell proliferation,cell cycle and alkaline phosphatase(ALP)activity were observed in three groups of cells. Results High density BMSCs were successfully obtained by density gradient centrifugation and adherence screening.After transfection of BMSCs with bFGF gene, the cell morphology showed no significant changes, while the expressions of bFGF mRNA and protein were significantly increased, the cell proliferation curve shifted upward, the proportion of proliferating cells increased,and the activity of ALP was significantly enhanced.There were significant differences between three groups(P<0.05).Conclusion The rabbit bFGF gene is successfully introduced into the BMSCs cultured in vitro by lentiviral vector, and the target gene is stably expressed.The expression of bFGF can promote the proliferation and osteogenic differentiation of BMSCs.